胰胆管合流异常的临床和实验研究
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摘要
胰胆管合流异常是胰、胆管在十二指肠壁外汇合形成过长通道的先天性异常,十二指肠乳头部括约肌的作用不能影响整个合流部位,致使胆汁、胰液互流而引起胆胰系统疾病。如果共同通道长度成人≥15mm,小儿≥5mm,便认为是胰胆管合流异常。自1916年kozumi报告此病以来,人们对此进行了大量研究。然而胰胆管合流异常与其相关疾病如胰腺炎、胆石症、胆管炎、胆道癌、胆总管扩张等疾病的关系仍未明了,并且以往的研究大多限于临床病例资料及影像资料回顾。为此我们通过胎儿尸体解剖来了解胰胆管合流处的解剖,建立动物实验模型探讨胰胆管合流异常对肝胆胰的损伤,并对胰胆管合流异常动物进行抗氧化治疗,为临床进一步干预提供资料。
一、第一部分胎儿胰胆管解剖研究
目的:通过胎儿尸体解剖的研究,探讨胎儿胰胆管合流的类型及十二指肠乳头的形状和位置,了解这一区域的解剖特点。
方法:选取经水囊引产死后6h内的新鲜胎儿36例,胎龄4月～9月。切取包括胆囊、胆总管、十二指肠、胰腺的标本,观察十二指肠乳头的形状、位置。再置于福尔马林中24h,脱水、透明、浸腊、包埋。组织块以乳头为中心,横行连续切片,厚6μm,每隔5张选一张,作HE染色。显微镜下观察胰胆管合流的类型。
结果:1)十二指肠大乳头有半球形21例(58.1%),圆柱形9例(25%),扁平形6例(16.9%)三种形态。乳头位于十二指肠降部上1/3部3例(8.3%),中1/3部25例(69.4%),下1/3部7例(19.4%),远部1例(2.9%)。
2)存在U、V、Y和异常合流四种胰胆管合流方式,其中以Y型24例(66.7%),V型7例(19.4%),U形4例(11.1%),APBDU1例(2.8%)。
结论:乳头形态位置及胰胆管合流的类型变化较多,了解这一解剖在临床有重要的意义。
二、第二部分PCNA在胆管上皮细胞的表达
目的:通过先天性胆总管囊肿,胆管癌和流产胎儿胆管三种标本的免疫组织化学染色,探讨PCNA在胆管黏膜上皮细胞的表达,了解胆管上皮细胞的增殖分化情况。
方法:取先天性胆总管囊肿标本20例,胆管癌标本8例,流产胎儿胆管标本20例,福尔马林固定24h。标本常规石蜡包埋,切片,切片厚度3μm。作PCNA免疫组化染色。
结果:PCNA阳性染色细胞核为棕色。正常胎儿胆管的表达为5.45%±1.90%,先天性胆总管囊肿的表达为47.75%±5.48%,胆管癌的表达为83.88%±7.24%。三组间的表达不同,有统计学意义。
结论:PCNA在三种细胞的表达不同,先天性胆总管囊肿的上皮细胞处于增殖状态,PCNA是一种衡量细胞增殖的灵敏指标。
三、第三部分胰胆管合流异常动物模型的建立
目的:建立更为符合人类胰胆管合流异常特点的动物模型。
方法:选用建康杂种猫15只,3月～1岁,体重3.2～5.0公斤,雌雄不限。术前禁食12h,3.5%戊巴比妥钠麻醉后,取上腹正中切口切开各层至腹腔。于胆总管进入十二指肠处旁边,切开胰腺背膜,解剖胰管,靠近十二指肠处分别纵向切开胰管、胆管长约4mm～6mm的切口。6-0线间断吻合切口,造成类似人类的胰胆管汇合的共同通道。术后20天胆道造影。
结果:11只猫术后精神、食欲良好,无萎靡、烦燥等表现,造影显示胰胆管合流共同通道延长。4只于术后3、5天死亡。
结论:本动物模型更接近于人类的胰胆管合流异常生理解剖,优于其他动物模型。
四、第四部分胰胆管合流异常肝胆胰损伤的实验研究
目的:建立更为符合人类胰胆管合流异常特点的动物模型后,观察胰胆管合流异常对肝、胆和胰腺的损伤。
方法:选择10只健康杂种猫,建立胰胆管合流异常的动物模型,饲养6个月。分别于手术前及6个月后取肝、胆囊和胰腺作HE,电镜切片,测定组织中MDA,胆汁淀粉酶、PCNA,观察病理变化。
结果:7只猫成活,肝胆胰都发生了明显变化。
1)肝脏的变化。手术前肝脏呈淡红色,质软。6月后肝脏颜色加深、呈暗红色,有粟粒结节样改变,质地变韧。光镜下手术前肝细胞结构形态正常,无细胞变性坏死,少量炎性细胞浸润。6个月后可见大量肝细胞气球样变,炎性细胞浸润。术后6月病理切片的得分高于手术前(9:1),有统计学意义(P<0.05)。电镜下术后6个月肝细胞胞浆内出现大量脂滴;线粒体肿胀、固缩;内质网扩张囊泡化、脱颗粒;有胶原形成。
2)胰腺的变化。手术前胰腺呈粉红色,表面看不到胰管。6月后胰腺颜色加重,充血、水肿,3例可见扩张的胰管。光镜下有3例可见炎性细胞浸润,4例间质血管增生、白细胞附壁。电镜下粗面内质网扩张,有的呈池状;线粒体数量增多,体积增大,崩解;高尔基复合体发达,数量增多。
3)胆道的变化。6个月后胆管增粗,胆囊壁增厚,囊内胆汁稠后。光镜下手术前黏膜呈指状,数目少,无增生;6各月后上皮、黏膜增生及炎细胞浸润。电镜下手术前上皮细胞排列紧密、规则。6月后内质网扩张成囊状,细胞间隙增宽,细胞核变形。淀粉酶、PCNA计数明显高于手术前(手术前为192.08±62.04IU,7.29%±2.70%.6个月后为9368.09±2204.42IU,54.71%±10.90%.P<0.05)。
结论:胰胆管合流异常时对肝、胆、胰有损伤。
五、第五部分抗氧化对胰胆管合流异常损伤的实验研究
目的:对胰胆管合流异常的动物模型进行抗氧化治疗,观察抗氧化治疗对胰胆管合流异常肝胆胰损伤的保护作拥。
方法:13只建立胰胆管合流异常动物模型的健康杂种猫,随机分为两组:A组7只不抗氧化治疗;B组6只给予抗氧化治疗(褪黑素1mg/kg/d,腹腔注射,3月后维生素C 500mg/kg/d,维生素E 500mg/kg/d口服);一般条件下饲养6个月。观察肝、胆和胰腺组织的病理变化和MDA含量,手术前13只的作为对照C组。
结果:建成的13只动物模型均成活6个月,两组肝胆胰的变化明显不同。
1)肝脏的变化:C组13只猫的肝脏呈淡红色,质软,表面无结节。A组7只猫的肝脏均颜色加深、呈暗红色,有粟粒结节样改变,质地变韧。B组中有2只与A组猫无差别,另4只肝脏有针尖样小结节,颜色与A组比明显好转。光镜下C组肝细胞结构形态正常,无细胞变性坏死,少量炎性细胞浸润。A组7只猫可见大量肝细胞气球样变,炎性细胞浸润。B组2只镜下与A组无差异,另5只气球样变细胞数目明显减少,没有坏死。电镜下B组脂滴数目,线粒体肿胀,内质网扩张程度都比A组减轻。A组的MDA ( 4.697±1.957 nmol/mgprot )明显高于对照组(1.273±0.889nmol/mgprot),而稍高于B组(0.789±0.860 nmol/mgprot),(P=0.001, F=17.43)。
2)胰腺的变化:对照组胰腺呈粉红色,表面看不到胰管。A组中胰腺颜色加重、不均匀,充血、水肿,3例可见扩张的胰管。B组胰腺颜色稍加重,无胰管扩张及腺体水肿。光镜下A组中有3例可见炎性细胞浸润,4例间质血管增生、白细胞附壁。B组未见炎性细胞浸润,2例间质血管内白细胞增多。电镜下A组粗面内质网扩张,有的呈池状;线粒体数量增多,体积增大,崩解;高尔基复合体发达,数量增多(图5-13、14);B组胰酶分泌减少,较A组减轻。B组MDA(0.927±0.880 nmol/mgprot)低于对照组(1.234±0.716nmol/mgprot)和A组(2.900±1.888 nmol/mgprot)。ANOVA检验,P=0.0215, F=4.80。
3)胆道的变化:A组较对照组胆管增粗,胆囊壁增厚,囊内胆汁稠后;B组和A组比无明显变化。光镜下对照组粘膜呈指状,数目少,无增生;A组上皮、黏膜增生及炎细胞浸润。部分胆管壁纤维组织增生。电镜下对照组上皮细胞排列紧密、规则。A组内质网扩张成囊状,细胞间隙增宽,细胞核变形,B组较A组好转。胆汁淀粉酶A组(9368.09±2204.42IU),B组(8746.25±2077.95IU)。t检验,P=0.642>0.05,无统计学意义。PCNA计数:对照组(7.29%±2.706%),A组(54.71%±10.90 %)高于B组(48.17%±13.06%)。ANOVA检验,P=0.001, F=48.11,有统计学意义(表5-4)。MDA:对照组1.095±0.653nmol/mgprot , A组2.745±1.533 nmol/mgprot , B组1.302±0.771nmol/mgprot。ANOVA检验,P=0.0168, F=5.17,有统计学意义。
结论:抗氧化治疗对APBDU有效。
Anomalous pancreaticobiliary ductal union is a congenital anomaly defined as common bile duct and pancreatic duct union that is located outside the duodenal wall and beyond the influence of the sphincter of Oddi. Normally, the common bile duct and pancreatic duct open into the duodenum via a common channel which is usually less 10 mm and it is considered anomalous when this is more than 15 mm in adults and 5 mm in children. What the sphincter of Oddi falls to prevent mutual reflux of bile and pancreatic juice into the pancreatic and bile ducts lead to some diseases such as congenital choledochal dilation, cholangitis and carcinoma of the gallbladder so on. Anomalous pancreaticobiliary ductal union had been studied fully in clinic since it was reported by Kozumi and Kodama in 1916.However the etiology and pathophysiology are still unknowen and most of researches are on the retrospective of the clinical features and imageing findings. In order to obtain more information, we investigate the pancreaticobiliary dissection in foetus to know the shapes and the locations of the greater duodenal papilla, the types of pancreaticobiliary ductal union. We also produce an animal model for anomalous pancreaticobiliary ductal union to study the injuries of livers, pancreas and gallbladders in cats with anomalous pancreaticobiliary ductal union. Besides, the anti-oxidative treatment in cats with anomalous pancreaticobiliary ductal union were evaluated here.
1.The study of pancreaticobiliary dissection in foetus
Objective: The pancreaticobiliary dissection in foetus were investigated to know the shapes and the locations of the greater duodenal papilla, the types of pancreaticobiliary ductal union.
Methods: 36 foetus who had died of induction of labor with water bag in 6 hours about 4 to 9 months old were studied. The specimens, including gallbladder, common bile duct, pancreatic duct and duodenum, were preserved in 10% buffered formaldehyde solution for 24 hours. Then the locations and shapes of the greater duodenal papilla were observed. Sections measuring 6μm were cut continuously from the paraffin-embedded tissue block, one was selected in every five sections and stained with hematoxylin and eosin. Then the sections were observed under the microscope.
Results: 1) The shapes of the greater duodenal papilla showed three kinds of patterns including hemispheroid(58.1%) , circular cylinder(25%) and applanation(16.9%).The greater duodenal papillas locataed at the upper pars descendens duodenum (8.3%),the middle pars descendens duodenum(69.4%),the lower pars descendens duodenum(19.4%) and the farer(2.9%).
2)The types of pancreaticobiliary ductal union were classified into four types , known as“Y”in 24 specimens(66.7%),“U”in 4 specimens(11.1%) ,“V”in 7 specimens(19.4%) and APBDU type in 1 specimens(2.8%).
Conclusions: There are many kinds of types in pancreaticobiliary ductal union which has great clinical significance.
2.Expression of proliferating cell nuclear antigen in epithelial cells of bile duct
Objective: To examine the proliferation and differentiation of epithelial cells in bile duct by checking their expression of proliferating cell nuclear antigen through the cases of congenital biliary dilatation, biliary cancer and normal bile duct.
Methods: 20 cases of congenital biliary dilatation, 8 cases of biliary cancer and 20 cases of normal bile duct were studied in the experiment. The specimens were preserved in 10%buffered formaldehyde solution for 24 hours, embedded in paraffin, slided 3μm thick for proliferating cell nuclear antigen histochemical studies.
Results: Proliferating cell nuclear antigen labeling was 5.45%±1.90% in 20 cases of normal bile duct,47.75%±5.48% in 20 cases of congenital biliary dilatation and 83.88%±7.24% in 8 cases of biliary cancer. The expression of proliferating cell nuclear antigen showed a highly difference among them.
Conclusions: There are difference expression of proliferating cell nuclear antigen in these three kinds of epithelial cells of bile duct. Proliferating cell nuclear antigen may be a better indicater to evaluate the proliferation and differentiation of epithelial cells in bile duct
3.An animal model for anomalous pancreaticobiliary ductal union.
Objective: To produce an animal model for anomalous pancreaticobiliary ductal union.
Methods: 15 healthy cats, fasted about 12 hours before operation, anaesthetized by 3.5% pentobarbital sodium(1.3ml/kg body-weight) were performed in the experiment, whose abdominal wall were opened by a vertical incision of approximately 6 cm. The capsule of pancreas was opened to expose the pancreatic duct near which the common bile duct enters the duodenum. A 4- to 6-mm incision was made in the pancreatic duct and the common bile duct. The incised edges were anastomosed with continuous 6-0 nylon monofilament suture to make a wide and long communication between the pancreatic duct and the common bile duct, resembling the common channel of anomalous pancreaticobiliary ductal union in humans. The cholangiography was made in 20 days later of operation.
Results: After being operated, 11of cats had good spirit and appetite without showing dispirited and fantod. The cholangiography showed that there were a wide and long communication between the pancreatic duct and the common bile duct.4 cats died at the day of the operation.
Conclusions: This animal model for anomalous pancreaticobiliary ductal union is better than the other model.
4.The experimental study on the injuries of livers, pancreas and gallbladders in cats with anomalous pancreaticobiliary ductal union
Objective: To study the injuries of livers, pancreas and gallbladders in cats with anomalous pancreaticobiliary ductal union.
Methods: 10 healthy cats which were made a wide and long communication between the pancreatic duct and the common bile duct, resembling the common channel of anomalous pancreaticobiliary ductal union in humans were performed in the experiment. After 6 months, the livers, pancreas and gallbladders of these animals were removed and histopathological changes were evaluated by pathological and electron microscopic examination. Amylase in bile ,PCNA and the level of MDA were tested.
Results: Seven out of 10 cats survived surgery and remained alive for 6 months with significant changes observed.
1)The changes in livers. Before operation, the color of liver was salmon pink and there were no nodus in liver. The normal hepatic cells without steatosis were observed under a light microscope. However, the color became deeper and a little nodus were founded in liver 6 months later. Histopathology showed ballooning changes and inflammatory infiltrated in liver cells. The scores of histopathology were higher than before operation (9:1) with marked differences(P<0.05). Mitochondria swelling and lipid droplet in intracytoplasm were observed under an electron microscope.
2) The changes in pancreas. Before operation, the color of pancreas was salmon pink and the pancreatic duct was not found in the face of pancreas. The normal pancreatic cells without inflammation were observed under a light microscope. 6 months later, the pancreas became deeper in color with hyperaemia and hydroncus, which three of them could found the dilated pancreatic duct in the face of pancreas. Histopathology showed that three of cases were mixed inflammatory infiltrate with numerous neutrophils, vascular proliferation in four cases.
3)The changes in biliary tract. 6 months later, the wall of gallbladder became thicker, the bile became thicker. The amylase concentration in the gallbladder bile 6 months later was significantly higher than that before operation(192.08±62.04IU vs 9368.09±2204.42IU.P<0.05). The gallbladder epithelium became villous in appearance 6 months later, although the epithelium of that before operation was flat with few folds. The epithelial cells of gallbladder arranged tightly, although 6 months later a significant change such as endoplasmic reticulum expanding, intercellular space broadening and cellular nucleus deforming. The positive cells of proliferating cell nuclear antigen were increased significantly in the gallbladder epithelium at 6 months later(7.29%±2.70% vs 54.71%±10.90%.P<0.05).
Conclusions: This animal model demonstrated that anomalous pancreaticobiliary ductal union would be harmful to the liver, pancreas and gallbladder.
5. The experimental study on the anti-oxidative to the injuries of anomalous pancreaticobiliary ductal union
Objective: To evaluate the anti-oxidative treatment in cats with anomalous pancreaticobiliary ductal union.
Methods: 13 healthy cats which had been made a wide and long communication between the pancreatic duct and the common bile duct, resembling the common channel of anomalous pancreaticobiliary ductal union in humans were divided randomly into two groups: 7 cats in group A were not treated. 6 cats in group B were treated with melatonin injected intraperitoneally (1mg/kg/d) three months, and breeded with vitamin C(500mg/kg/d) and vitamin E(500mg/kg/d) in next three months. After 6 months, the livers, pancreas and gallbladders of these animals were removed and histopathological changes were evaluated by pathological and electron microscopic examination. The level of MDA were tested
Results: 1)The changes in livers. 13 cats in control group showed that the color of live was salmon pink and no nodus in liver. In A group, the color of liver became deeper and a little nodus was founded in liver. Histopathology showed ballooning changes in liver cells, mitochondria swelling and lipid droplet in intracytoplasm.1 of cats in group B had the same changes as the group A, The other 5 cats had less changes than that in group A both in pathological and electron microscopic examination.
2) The changes in pancreas. In control group, the color of pancreas was salmon pink and the pancreatic duct was not found in the face of pancreas.In group A, the pancreas became deeper in color with hyperaemia and hydroncus, which three of them could found the dilated pancreatic duct in the face of pancreas. In group B, no dilated pancreatic duct and hydroncus were found. Histopathology showed that three of cases were mixed inflammatory infiltrate with numerous neutrophils, vascular proliferation in four cases in group A. but no changes were found in group B.
3)The changes in biliary tract. The wall of gallbladder became thicker and the bile became thicker in group A than that in control group. There were no differences between the group of A and B. The amylase concentration in the gallbladder bile was 9368.09±2204.42 IU in group A and 8746.25±2077.95 IU in group B. The gallbladder epithelium became villous in appearance with in group A, although the epithelium of that in group of control was flat with few folds. The epithelial cells of gallbladder arranged tightly in control group, while a significant change such as endoplasmic reticulum expanding, intercellular space broadening and cellular nucleus deforming were observed in group A. The things in group B were better in group A. The positive cells of proliferating cell nuclear antigen were 7.29%±2.70% in control,54.71%±10.90 % in group A, 48.17%±13.06% in group B. The levels of MDA were 1.095±0.653nmol/mgprot in control,2.745±1.533 nmol/mgprot in group A ,1.302±0.771nmol/mgprot in group B.
Conclusions: The anti-oxidative treatment was effective to the anomalous pancreaticobiliary ductal unionl.
一、第一部分胎儿胰胆管解剖研究
目的:通过胎儿尸体解剖的研究,探讨胎儿胰胆管合流的类型及十二指肠乳头的形状和位置,了解这一区域的解剖特点。
方法:选取经水囊引产死后6h内的新鲜胎儿36例,胎龄4月～9月。切取包括胆囊、胆总管、十二指肠、胰腺的标本,观察十二指肠乳头的形状、位置。再置于福尔马林中24h,脱水、透明、浸腊、包埋。组织块以乳头为中心,横行连续切片,厚6μm,每隔5张选一张,作HE染色。显微镜下观察胰胆管合流的类型。
结果:1)十二指肠大乳头有半球形21例(58.1%),圆柱形9例(25%),扁平形6例(16.9%)三种形态。乳头位于十二指肠降部上1/3部3例(8.3%),中1/3部25例(69.4%),下1/3部7例(19.4%),远部1例(2.9%)。
2)存在U、V、Y和异常合流四种胰胆管合流方式,其中以Y型24例(66.7%),V型7例(19.4%),U形4例(11.1%),APBDU1例(2.8%)。
结论:乳头形态位置及胰胆管合流的类型变化较多,了解这一解剖在临床有重要的意义。
二、第二部分PCNA在胆管上皮细胞的表达
目的:通过先天性胆总管囊肿,胆管癌和流产胎儿胆管三种标本的免疫组织化学染色,探讨PCNA在胆管黏膜上皮细胞的表达,了解胆管上皮细胞的增殖分化情况。
方法:取先天性胆总管囊肿标本20例,胆管癌标本8例,流产胎儿胆管标本20例,福尔马林固定24h。标本常规石蜡包埋,切片,切片厚度3μm。作PCNA免疫组化染色。
结果:PCNA阳性染色细胞核为棕色。正常胎儿胆管的表达为5.45%±1.90%,先天性胆总管囊肿的表达为47.75%±5.48%,胆管癌的表达为83.88%±7.24%。三组间的表达不同,有统计学意义。
结论:PCNA在三种细胞的表达不同,先天性胆总管囊肿的上皮细胞处于增殖状态,PCNA是一种衡量细胞增殖的灵敏指标。
三、第三部分胰胆管合流异常动物模型的建立
目的:建立更为符合人类胰胆管合流异常特点的动物模型。
方法:选用建康杂种猫15只,3月～1岁,体重3.2～5.0公斤,雌雄不限。术前禁食12h,3.5%戊巴比妥钠麻醉后,取上腹正中切口切开各层至腹腔。于胆总管进入十二指肠处旁边,切开胰腺背膜,解剖胰管,靠近十二指肠处分别纵向切开胰管、胆管长约4mm～6mm的切口。6-0线间断吻合切口,造成类似人类的胰胆管汇合的共同通道。术后20天胆道造影。
结果:11只猫术后精神、食欲良好,无萎靡、烦燥等表现,造影显示胰胆管合流共同通道延长。4只于术后3、5天死亡。
结论:本动物模型更接近于人类的胰胆管合流异常生理解剖,优于其他动物模型。
四、第四部分胰胆管合流异常肝胆胰损伤的实验研究
目的:建立更为符合人类胰胆管合流异常特点的动物模型后,观察胰胆管合流异常对肝、胆和胰腺的损伤。
方法:选择10只健康杂种猫,建立胰胆管合流异常的动物模型,饲养6个月。分别于手术前及6个月后取肝、胆囊和胰腺作HE,电镜切片,测定组织中MDA,胆汁淀粉酶、PCNA,观察病理变化。
结果:7只猫成活,肝胆胰都发生了明显变化。
1)肝脏的变化。手术前肝脏呈淡红色,质软。6月后肝脏颜色加深、呈暗红色,有粟粒结节样改变,质地变韧。光镜下手术前肝细胞结构形态正常,无细胞变性坏死,少量炎性细胞浸润。6个月后可见大量肝细胞气球样变,炎性细胞浸润。术后6月病理切片的得分高于手术前(9:1),有统计学意义(P<0.05)。电镜下术后6个月肝细胞胞浆内出现大量脂滴;线粒体肿胀、固缩;内质网扩张囊泡化、脱颗粒;有胶原形成。
2)胰腺的变化。手术前胰腺呈粉红色,表面看不到胰管。6月后胰腺颜色加重,充血、水肿,3例可见扩张的胰管。光镜下有3例可见炎性细胞浸润,4例间质血管增生、白细胞附壁。电镜下粗面内质网扩张,有的呈池状;线粒体数量增多,体积增大,崩解;高尔基复合体发达,数量增多。
3)胆道的变化。6个月后胆管增粗,胆囊壁增厚,囊内胆汁稠后。光镜下手术前黏膜呈指状,数目少,无增生;6各月后上皮、黏膜增生及炎细胞浸润。电镜下手术前上皮细胞排列紧密、规则。6月后内质网扩张成囊状,细胞间隙增宽,细胞核变形。淀粉酶、PCNA计数明显高于手术前(手术前为192.08±62.04IU,7.29%±2.70%.6个月后为9368.09±2204.42IU,54.71%±10.90%.P<0.05)。
结论:胰胆管合流异常时对肝、胆、胰有损伤。
五、第五部分抗氧化对胰胆管合流异常损伤的实验研究
目的:对胰胆管合流异常的动物模型进行抗氧化治疗,观察抗氧化治疗对胰胆管合流异常肝胆胰损伤的保护作拥。
方法:13只建立胰胆管合流异常动物模型的健康杂种猫,随机分为两组:A组7只不抗氧化治疗;B组6只给予抗氧化治疗(褪黑素1mg/kg/d,腹腔注射,3月后维生素C 500mg/kg/d,维生素E 500mg/kg/d口服);一般条件下饲养6个月。观察肝、胆和胰腺组织的病理变化和MDA含量,手术前13只的作为对照C组。
结果:建成的13只动物模型均成活6个月,两组肝胆胰的变化明显不同。
1)肝脏的变化:C组13只猫的肝脏呈淡红色,质软,表面无结节。A组7只猫的肝脏均颜色加深、呈暗红色,有粟粒结节样改变,质地变韧。B组中有2只与A组猫无差别,另4只肝脏有针尖样小结节,颜色与A组比明显好转。光镜下C组肝细胞结构形态正常,无细胞变性坏死,少量炎性细胞浸润。A组7只猫可见大量肝细胞气球样变,炎性细胞浸润。B组2只镜下与A组无差异,另5只气球样变细胞数目明显减少,没有坏死。电镜下B组脂滴数目,线粒体肿胀,内质网扩张程度都比A组减轻。A组的MDA ( 4.697±1.957 nmol/mgprot )明显高于对照组(1.273±0.889nmol/mgprot),而稍高于B组(0.789±0.860 nmol/mgprot),(P=0.001, F=17.43)。
2)胰腺的变化:对照组胰腺呈粉红色,表面看不到胰管。A组中胰腺颜色加重、不均匀,充血、水肿,3例可见扩张的胰管。B组胰腺颜色稍加重,无胰管扩张及腺体水肿。光镜下A组中有3例可见炎性细胞浸润,4例间质血管增生、白细胞附壁。B组未见炎性细胞浸润,2例间质血管内白细胞增多。电镜下A组粗面内质网扩张,有的呈池状;线粒体数量增多,体积增大,崩解;高尔基复合体发达,数量增多(图5-13、14);B组胰酶分泌减少,较A组减轻。B组MDA(0.927±0.880 nmol/mgprot)低于对照组(1.234±0.716nmol/mgprot)和A组(2.900±1.888 nmol/mgprot)。ANOVA检验,P=0.0215, F=4.80。
3)胆道的变化:A组较对照组胆管增粗,胆囊壁增厚,囊内胆汁稠后;B组和A组比无明显变化。光镜下对照组粘膜呈指状,数目少,无增生;A组上皮、黏膜增生及炎细胞浸润。部分胆管壁纤维组织增生。电镜下对照组上皮细胞排列紧密、规则。A组内质网扩张成囊状,细胞间隙增宽,细胞核变形,B组较A组好转。胆汁淀粉酶A组(9368.09±2204.42IU),B组(8746.25±2077.95IU)。t检验,P=0.642>0.05,无统计学意义。PCNA计数:对照组(7.29%±2.706%),A组(54.71%±10.90 %)高于B组(48.17%±13.06%)。ANOVA检验,P=0.001, F=48.11,有统计学意义(表5-4)。MDA:对照组1.095±0.653nmol/mgprot , A组2.745±1.533 nmol/mgprot , B组1.302±0.771nmol/mgprot。ANOVA检验,P=0.0168, F=5.17,有统计学意义。
结论:抗氧化治疗对APBDU有效。
Anomalous pancreaticobiliary ductal union is a congenital anomaly defined as common bile duct and pancreatic duct union that is located outside the duodenal wall and beyond the influence of the sphincter of Oddi. Normally, the common bile duct and pancreatic duct open into the duodenum via a common channel which is usually less 10 mm and it is considered anomalous when this is more than 15 mm in adults and 5 mm in children. What the sphincter of Oddi falls to prevent mutual reflux of bile and pancreatic juice into the pancreatic and bile ducts lead to some diseases such as congenital choledochal dilation, cholangitis and carcinoma of the gallbladder so on. Anomalous pancreaticobiliary ductal union had been studied fully in clinic since it was reported by Kozumi and Kodama in 1916.However the etiology and pathophysiology are still unknowen and most of researches are on the retrospective of the clinical features and imageing findings. In order to obtain more information, we investigate the pancreaticobiliary dissection in foetus to know the shapes and the locations of the greater duodenal papilla, the types of pancreaticobiliary ductal union. We also produce an animal model for anomalous pancreaticobiliary ductal union to study the injuries of livers, pancreas and gallbladders in cats with anomalous pancreaticobiliary ductal union. Besides, the anti-oxidative treatment in cats with anomalous pancreaticobiliary ductal union were evaluated here.
1.The study of pancreaticobiliary dissection in foetus
Objective: The pancreaticobiliary dissection in foetus were investigated to know the shapes and the locations of the greater duodenal papilla, the types of pancreaticobiliary ductal union.
Methods: 36 foetus who had died of induction of labor with water bag in 6 hours about 4 to 9 months old were studied. The specimens, including gallbladder, common bile duct, pancreatic duct and duodenum, were preserved in 10% buffered formaldehyde solution for 24 hours. Then the locations and shapes of the greater duodenal papilla were observed. Sections measuring 6μm were cut continuously from the paraffin-embedded tissue block, one was selected in every five sections and stained with hematoxylin and eosin. Then the sections were observed under the microscope.
Results: 1) The shapes of the greater duodenal papilla showed three kinds of patterns including hemispheroid(58.1%) , circular cylinder(25%) and applanation(16.9%).The greater duodenal papillas locataed at the upper pars descendens duodenum (8.3%),the middle pars descendens duodenum(69.4%),the lower pars descendens duodenum(19.4%) and the farer(2.9%).
2)The types of pancreaticobiliary ductal union were classified into four types , known as“Y”in 24 specimens(66.7%),“U”in 4 specimens(11.1%) ,“V”in 7 specimens(19.4%) and APBDU type in 1 specimens(2.8%).
Conclusions: There are many kinds of types in pancreaticobiliary ductal union which has great clinical significance.
2.Expression of proliferating cell nuclear antigen in epithelial cells of bile duct
Objective: To examine the proliferation and differentiation of epithelial cells in bile duct by checking their expression of proliferating cell nuclear antigen through the cases of congenital biliary dilatation, biliary cancer and normal bile duct.
Methods: 20 cases of congenital biliary dilatation, 8 cases of biliary cancer and 20 cases of normal bile duct were studied in the experiment. The specimens were preserved in 10%buffered formaldehyde solution for 24 hours, embedded in paraffin, slided 3μm thick for proliferating cell nuclear antigen histochemical studies.
Results: Proliferating cell nuclear antigen labeling was 5.45%±1.90% in 20 cases of normal bile duct,47.75%±5.48% in 20 cases of congenital biliary dilatation and 83.88%±7.24% in 8 cases of biliary cancer. The expression of proliferating cell nuclear antigen showed a highly difference among them.
Conclusions: There are difference expression of proliferating cell nuclear antigen in these three kinds of epithelial cells of bile duct. Proliferating cell nuclear antigen may be a better indicater to evaluate the proliferation and differentiation of epithelial cells in bile duct
3.An animal model for anomalous pancreaticobiliary ductal union.
Objective: To produce an animal model for anomalous pancreaticobiliary ductal union.
Methods: 15 healthy cats, fasted about 12 hours before operation, anaesthetized by 3.5% pentobarbital sodium(1.3ml/kg body-weight) were performed in the experiment, whose abdominal wall were opened by a vertical incision of approximately 6 cm. The capsule of pancreas was opened to expose the pancreatic duct near which the common bile duct enters the duodenum. A 4- to 6-mm incision was made in the pancreatic duct and the common bile duct. The incised edges were anastomosed with continuous 6-0 nylon monofilament suture to make a wide and long communication between the pancreatic duct and the common bile duct, resembling the common channel of anomalous pancreaticobiliary ductal union in humans. The cholangiography was made in 20 days later of operation.
Results: After being operated, 11of cats had good spirit and appetite without showing dispirited and fantod. The cholangiography showed that there were a wide and long communication between the pancreatic duct and the common bile duct.4 cats died at the day of the operation.
Conclusions: This animal model for anomalous pancreaticobiliary ductal union is better than the other model.
4.The experimental study on the injuries of livers, pancreas and gallbladders in cats with anomalous pancreaticobiliary ductal union
Objective: To study the injuries of livers, pancreas and gallbladders in cats with anomalous pancreaticobiliary ductal union.
Methods: 10 healthy cats which were made a wide and long communication between the pancreatic duct and the common bile duct, resembling the common channel of anomalous pancreaticobiliary ductal union in humans were performed in the experiment. After 6 months, the livers, pancreas and gallbladders of these animals were removed and histopathological changes were evaluated by pathological and electron microscopic examination. Amylase in bile ,PCNA and the level of MDA were tested.
Results: Seven out of 10 cats survived surgery and remained alive for 6 months with significant changes observed.
1)The changes in livers. Before operation, the color of liver was salmon pink and there were no nodus in liver. The normal hepatic cells without steatosis were observed under a light microscope. However, the color became deeper and a little nodus were founded in liver 6 months later. Histopathology showed ballooning changes and inflammatory infiltrated in liver cells. The scores of histopathology were higher than before operation (9:1) with marked differences(P<0.05). Mitochondria swelling and lipid droplet in intracytoplasm were observed under an electron microscope.
2) The changes in pancreas. Before operation, the color of pancreas was salmon pink and the pancreatic duct was not found in the face of pancreas. The normal pancreatic cells without inflammation were observed under a light microscope. 6 months later, the pancreas became deeper in color with hyperaemia and hydroncus, which three of them could found the dilated pancreatic duct in the face of pancreas. Histopathology showed that three of cases were mixed inflammatory infiltrate with numerous neutrophils, vascular proliferation in four cases.
3)The changes in biliary tract. 6 months later, the wall of gallbladder became thicker, the bile became thicker. The amylase concentration in the gallbladder bile 6 months later was significantly higher than that before operation(192.08±62.04IU vs 9368.09±2204.42IU.P<0.05). The gallbladder epithelium became villous in appearance 6 months later, although the epithelium of that before operation was flat with few folds. The epithelial cells of gallbladder arranged tightly, although 6 months later a significant change such as endoplasmic reticulum expanding, intercellular space broadening and cellular nucleus deforming. The positive cells of proliferating cell nuclear antigen were increased significantly in the gallbladder epithelium at 6 months later(7.29%±2.70% vs 54.71%±10.90%.P<0.05).
Conclusions: This animal model demonstrated that anomalous pancreaticobiliary ductal union would be harmful to the liver, pancreas and gallbladder.
5. The experimental study on the anti-oxidative to the injuries of anomalous pancreaticobiliary ductal union
Objective: To evaluate the anti-oxidative treatment in cats with anomalous pancreaticobiliary ductal union.
Methods: 13 healthy cats which had been made a wide and long communication between the pancreatic duct and the common bile duct, resembling the common channel of anomalous pancreaticobiliary ductal union in humans were divided randomly into two groups: 7 cats in group A were not treated. 6 cats in group B were treated with melatonin injected intraperitoneally (1mg/kg/d) three months, and breeded with vitamin C(500mg/kg/d) and vitamin E(500mg/kg/d) in next three months. After 6 months, the livers, pancreas and gallbladders of these animals were removed and histopathological changes were evaluated by pathological and electron microscopic examination. The level of MDA were tested
Results: 1)The changes in livers. 13 cats in control group showed that the color of live was salmon pink and no nodus in liver. In A group, the color of liver became deeper and a little nodus was founded in liver. Histopathology showed ballooning changes in liver cells, mitochondria swelling and lipid droplet in intracytoplasm.1 of cats in group B had the same changes as the group A, The other 5 cats had less changes than that in group A both in pathological and electron microscopic examination.
2) The changes in pancreas. In control group, the color of pancreas was salmon pink and the pancreatic duct was not found in the face of pancreas.In group A, the pancreas became deeper in color with hyperaemia and hydroncus, which three of them could found the dilated pancreatic duct in the face of pancreas. In group B, no dilated pancreatic duct and hydroncus were found. Histopathology showed that three of cases were mixed inflammatory infiltrate with numerous neutrophils, vascular proliferation in four cases in group A. but no changes were found in group B.
3)The changes in biliary tract. The wall of gallbladder became thicker and the bile became thicker in group A than that in control group. There were no differences between the group of A and B. The amylase concentration in the gallbladder bile was 9368.09±2204.42 IU in group A and 8746.25±2077.95 IU in group B. The gallbladder epithelium became villous in appearance with in group A, although the epithelium of that in group of control was flat with few folds. The epithelial cells of gallbladder arranged tightly in control group, while a significant change such as endoplasmic reticulum expanding, intercellular space broadening and cellular nucleus deforming were observed in group A. The things in group B were better in group A. The positive cells of proliferating cell nuclear antigen were 7.29%±2.70% in control,54.71%±10.90 % in group A, 48.17%±13.06% in group B. The levels of MDA were 1.095±0.653nmol/mgprot in control,2.745±1.533 nmol/mgprot in group A ,1.302±0.771nmol/mgprot in group B.
Conclusions: The anti-oxidative treatment was effective to the anomalous pancreaticobiliary ductal unionl.
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