基于肺与胃肠相关理论探讨银莱汤对食积肺炎动物模型肠黏膜屏障作用机制
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摘要
银莱汤是导师谷晓红教授在临床上治疗肺与胃肠积热证的经验方。肺与胃肠具有相关性,阳明胃肠积热是发生肺热证的重要因素之一,银莱汤立足于肺与胃肠同治理论,在治疗肺热证时注重清泄阳明内热。该方在临床上治疗肺与胃肠积热证具有较好疗效,尤其在儿科疾病中应用广泛,如小儿外感、小儿肺炎、小儿反复呼吸道感染等。本研究基于肺与胃肠相关理论及肺与胃肠同治思路,建立食积复合病毒性肺炎动物模型,观察动物模型肠黏膜屏障的病理变化,探讨银莱汤对动物模型肠黏膜屏障的作用机制,为银莱汤的临床应用提供可靠的理论和实验依据,对于肺与胃肠同治法指导相关疾病的防治具有重要的实用价值。
论文共分为理论探讨、文献综述、实验研究三个部分。
第一部分理论探讨
结合中西医相关文献资料,对肺与胃肠相关理论从中医学、西医学以及临床应用三个方面进行探讨和论述。肺与胃肠相关理论源于《黄帝内经》,肺与胃肠经络循行相连,形态结构相近,生理功能相合,并且在气机失调、水液失常、饮食积滞等病理变化上密切相关。随着现代科学技术的发展,肺与胃肠相关理论的现代机理研究更加深入,肺与胃肠在胚胎发育、内分泌调节、黏膜免疫、炎症反应、内毒素损伤、神经调节、气体排泄等方面关系密切。肺与胃肠相关理论一直有效地指导着临床实践,许多呼吸系统常见病,如小儿外感、小儿肺炎、小儿反复呼吸道感染、慢性阻塞性肺病、支气管哮喘等,以及消化系统疾病,如便秘、溃疡性结肠炎、肠易激综合征、胃食管反流病等,利用肺与胃肠同治理论指导治疗,均能够取得较好疗效。
第二部分文献综述
从两个方面进行论述：一、从发病病因、动物模型、现代机理、食积相关肺系热病等方面对小儿食积进行综述,为临床防治食积及食积相关肺系热病奠定理论基础。二、从肠黏膜屏障的组成、生理功能以及肠黏膜屏障功能障碍的损伤机理、中医药治疗等方面进行论述,为探讨银莱汤对动物模型肠黏膜屏障作用机制提供理论依据。
第三部分实验研究
目的：通过建立食积复合病毒性肺炎动物模型,观察动物模型肠黏膜的病理变化,探讨银莱汤对动物模型肠黏膜机械屏障和免疫屏障的作用机制。
方法：通过病因模拟制作肺与胃肠积热动物模型,先予小鼠高蛋白高热量饮食,制作食积模型(阳明胃肠积热证),在此基础上,小鼠乙醚麻醉后经鼻感染流感病毒,制作食积复合病毒性肺炎模型(肺与胃肠积热证)。通过给予银莱汤治疗,观察动物模型的肠黏膜屏障变化情况。实验分为正常组、感染组、食积组、食积感染组、食积治疗组、食积感染治疗组。为研究肠黏膜机械屏障变化,观察小鼠肠组织形态学、肠组织ZO-1水平及血清内毒素水平；为研究肠黏膜免疫屏障变化,观察小鼠肠组织sIgA水平及肠组织细胞因子TNF-a、IL-10水平
结果
肠组织形态学观察：肉眼观察肠黏膜形态,实验各组小鼠肠黏膜结构完整、表面光滑,未见充血、水肿、糜烂、溃疡等病理改变。电子显微镜下观察肠组织切片,正常组与感染组小鼠肠组织结构清晰完整,单层柱状上皮细胞及杯状细胞排列致密整齐,黏膜层无充血、水肿、炎性细胞浸润等病理改变；与正常组比较,食积组与食积感染组小鼠肠组织单层柱状上皮细胞及杯状细胞增大增多,排列紊乱；食积治疗组及食积感染治疗组小鼠肠组织单层柱状上皮细胞、杯状细胞较食积组及食积感染组数量减少、排列整齐。
肠组织ZO-1检测：与正常组比较,食积组与食积感染组小鼠肠组织ZO-1水平显著下降(P<0.01),食积感染治疗组显著升高(P<0.01),感染组与食积治疗组无明显差异(P>0.05)；食积治疗组显著高于食积组(P<0.01)；食积感染治疗组显著高于食积感染组(P<0.01)；食积感染治疗组显著高于食积治疗组(P<0.01)。
血清内毒素检测：与正常组小鼠比较,各组小鼠血清内毒素水平均有不同程度升高,其中食积感染组升高幅度最大,食积治疗组升高幅度最小,但各组之间比较均无显著性差异(P>0.05)。
肠组织sIgA检测：与正常组比较,食积组与食积感染组小鼠的肠组织sIgA水平显著下降(P<0.01),感染组有下降趋势,但无统计学意义(P>0.05)；与感染组比较,食积组显著下降(P<0.01)；经银莱汤治疗后,小鼠肠组织sIgA水平显著升高,食积治疗组显著高于食积组(P<0.01),与正常组比较无显著性差异(P>0.05)；食积感染治疗组显著高于食积感染组(P<0.01),与正常组比较显著升高(P<0.01)；食积感染治疗组sIgA水平显著高于食积治疗组(P<0.01)。
肠组织TNF-a检测：与正常组比较,感染组、食积组及食积感染组小鼠的肠组织TNF-α水平均显著下降(P<0.01),但三组之间比较无显著性差异(P>0.05)；食积治疗组显著高于食积组(P<0.01),但低于正常组水平(P<0.01)；食积感染治疗组显著高于食积感染组(P<0.01),与正常组比较略有升高,但无显著性差异(P>0.05)；食积感染治疗组显著高于食积治疗组(P<0.01)。
肠组织IL-10检测：感染组、食积组及食积感染组小鼠的肠组织IL-10水平与正常组比较均显著下降(P<0.01),三组之间比较无显著性差异(P>0.05)；食积治疗组显著高于食积组(P<0.01)；食积感染治疗组显著高于食积感染组(P<0.01)；食积治疗组及食积感染治疗组与正常组比较无显著性差异(P>0.05),食积治疗组与食积感染治疗组之间比较无显著性差异(P>0.05)。
结论
1肺与胃肠积热状态下,肠黏膜组织形态无明显病理性损伤,但肠黏膜单层柱状上皮细胞及杯状细胞增大增多,排列紊乱,会影响肠黏膜的分泌功能。银莱汤能够降低肠黏膜单层柱状上皮细胞及杯状细胞数量,改善其分布状况,对肠黏膜分泌功能具有调节作用。
2肺与胃肠积热会造成肠黏膜机械屏障的损伤,使肠黏膜的通透性增加,但损伤较轻,不会造成内毒素血症,其损伤机制与肠黏膜上皮细胞间紧密连接蛋白ZO-1的破环有关。银莱汤能够修复肠黏膜ZO-1,从而降低肠黏膜的通透性,对肠黏膜机械屏障具有保护作用。
3肺与胃肠积热会造成肠黏膜免疫屏障的损伤,能够降低肠黏膜sIgA水平,抑制细胞因子TNF-α、IL-10的分泌,从而影响肠黏膜免疫功能。银莱汤能够增加肠黏膜分泌sIgA,适度调节细胞因子TNF-α、IL-10水平,从而增强肠黏膜局部免疫,对肠黏膜免疫屏障具有保护作用。
Yin Lai Tang (Ylt) is an empirical formula of Gu Xiaohong Professor who treats pyretic Lung-Stomach (intestine) syndrome. This formula which is based on the concurrent treatment theory of lung-stomach (intestine), which considers the significant factor of pyretic pulmonary syndrome as retention of heat in stomach and intestine of Yang Ming, attach more importance on purging endogenous heat from Yang Ming. Ylt has a better curative effect on treating pyretic Dyspepsia-Lung syndrome and is used comprehensively in pediatric disease such as infantile cold, infantile pneumonia, puerile recurrent respiratory infection and so on. This study investigates the change of Intestinal mucosal barrier in animal model and makes Ylt's mechanism on intestinal mucosal barrier explicit through building the animal model with infection and dyspepsia. This study provides the reliable experimental evidence on the theory of clinical application of Ylt and has the practical value on prevention and cure of respiratory disease.
The dissertation includes three parts:theoretical discussion, literature review and experimental research.
Part One Theoretical Discussion
The theory of lung-stomach (intestine) correlation was investigated and discussed through Chinese medicine, modern medicine and clinical application according to relevant literature and material in the past dynasties. This theory was from Huangdi Neijing. Thereafter, after more rounded investigation and discussion, the doctors in history found the following viewpoints. The meridians between lung and stomach (intestine) were related. The morphological structure of lung was highly related to stomach. The physiological functions were similar. The pathological changes are highly related in dry-heat impairing syndrome, disorder of qi and body fluid, dyspeptic retention and so on. With the development of modern science and technology, modern mechanism of Lung-stomach (intestine) correlation theory has been investigated further and lung-stomach (intestine) are highly related in embryonic development, endocrine regulation, mucosal immunity, inflammation, viral infect, neuroregulation, gas excretion. The theory of Lung-Stomach (intestine) correlation always provides effective guidance on clinical practice of Chinese medicine. Many diseases were cured effectively based on the theory of treating the disease of Lung-Stomach (intestine) with the same method, including many respiratory diseases, such as infantile cold, infantile pneumonia, puerile recurrent respiratory infection, chronic obstructive pulmonary disease, bronchial asthma, digestive disease such as constipation, ulcerative colitis, irritable bowel syndrome, gastroesophageal reflux disease and so on.
Part Two Literature Review
Two respects have been expounded. One respect:dyspepsia and related febrile diseases in pulmonary system have been discussed and summarized through cause of disease, animal model, and modern mechanism. The other respect:the composition and physiological function of intestine mucosal barrier were expounded as well as the damage mechanism and treatment of Chinese medicine, which provided theoretical evidence for investigating Ylt's mechanism on intestine mucosal barrier of animal model.
Part Three Experimental Research
Purpose:This study investigated the change of Intestinal mucosal barrier in animal model and made Ylt's mechanism on intestinal mucosal barrier explicit through building the animal model with dyspepsia and pneumonia.
Method:Animal model with heat retention was simulated through cause of disease. The mice were feeding food with high calorie to build the animal model with dyspepsia (pyretic Yang Ming Stomach-Intestine syndrome). Then the mice were given flu virus per nasal after etherization to build compound model with viral pneumonia and dyspepsia (pyretic Lung and Stomach intestine syndrome). The changes of intestine mucosal barrier in animal model were observed after the treatment of Ylt. Experiments include normal group, infective group, dyspeptic group, dyspeptic-infective group, dyspeptic and curative group, dyspeptic-infective and curative group. The intestinal histomorphology, ZO-1level of intestinal tissues, serum endotoxin level were observed to study the mechanical changes of intestine mucosal barrier. slgA level and cytokine TNF-a, IL-10level of intestinal tissues were observed to study the immune changes of intestine mucosal barrier.
Result:
Histomorphology of intestine tissue:Through visual observation of intestine mucosal morphous, the structure of the intestine mucosa were integrate and the surface was smooth. Also no pathological change of hyperemia, oedema, erosion, and ulcer occurred. Through observation of intestine tissue slice under an electron microscope the structure of intestine tissue of mice were clear and integrate in both normal and infective group, and simple columnar epithelium cells aligned in good order. Also there were many goblet cells aligning in good order and closely and no pathological change of hyperemia, oedema, inflammation, inflammatory cell infiltration and so on. Simple columnar epithelium cells in dyspeptic group and dyspeptic-infective group aligned in disorder and goblet cells increased and became bigger and align in disorder compared with normal group. In dyspeptic group and curative group, dyspeptic-infective and curative group, goblet cells became bigger. And Simple columnar epithelium cells and goblet cells aligned in disorder but more regularly than in dyspeptic group, dyspeptic-infective group.
ZO-1of intestine tissue:ZO-1level of intestine tissues of the mice significantly decreased (P<0.01) in both dyspeptic group and dyspeptic-infective group compared with normal group, but increased significantly in dyspeptic, infective and curative group (P<0.01). No significant differences were noted in infective group, dyspeptic and curative group (P>0.05). ZO-1level in dyspeptic and curative group was significantly higher than in dyspeptic group (P<0.01). ZO-1level in dyspeptic-infective and curative group was significantly higher than dyspeptic-infective group and dyspeptic group (P<0.01). ZO-1level in dyspeptic-infective and curative group was significantly higher than dyspeptic and curative group.
Serum endotoxin:Serum endotoxin level of each group increased to different extent compared with normal group, of which dyspeptic-infective group increased highest, dyspeptic and curative group increased lowest, but no significant differences were noted in each group.
sIgA of intestine tissue:Compared with normal group, slgA level of intestine tissues in dyspeptic group and dyspeptic-infective group decreased significantly (P<0.01), but no significant differences were noted in infective group(P>0.05). Compared with infective group, slgA level of intestine tissues in dyspeptic group decreased significantly (P<0.01). sIgA level in dyspeptic and curative group was significantly higher than in dyspeptic group (P <0.01), but no significant differences compared with normal group(P>0.05). slgA level in dyspeptic-infective and curative group was significantly higher than dyspeptic-infective group and normal group (P<0.01). slgA level in dyspeptic-infective and curative group was significantly higher than dyspeptic and curative group.
TNF-α of intestine tissue:Compared with normal group, TNF-α level in infective group, dyspeptic group and dyspeptic-infective group decreased significantly (P<0.01) but no significant difference was found in these three group (P>0.05). The data in dyspeptic and curative group was significantly higher than in dyspeptic group (P<0.01) but still lower than in noimal group (P<0.01). The data in dyspeptic-infective and curative group is significantly higher than in dyspeptic-infective group (P<0.01) and compared with normal group, no significant difference was found (P>0.05). The data in dyspeptic-infective and curative group was significantly higher than in dyspeptic and curative group.
IL-10of intestine tissue:IL-10level of intestine tissue in infective group, dyspeptic group and dyspeptic-infective group decreased significantly compared with normal group (P <0.01) and no significant differences was found in these three groups (P>0.05). The data in dyspeptic and curative group was significantly higher than in dyspeptic group. The data in dyspeptic-infective and curative was significantly higher than in dyspeptic-infective group. No significant difference was found in dyspeptic and curative group, dyspeptic-infective and curative group compared with normal group. No significant difference was found between dyspeptic and curative group and dyspeptic-infective and curative group.
Conclusion:
1If there was heat retention in lung, stomach and intestine, the morphous of intestine tissue had no pathological damage. But goblet cells in single columnar epithelium increased and became bigger, aligned in discord, which affected secretion of intestine mucosa. Ylt could improve the number and distribution of goblet cell and regulate the secretion of intestine mucosa.
2The heat retention of lung-stomach (intestine) caused the damage of intestine mucosal mechanism barrier and increased the permeability of intestine mucosa. But the damage was very light and did not cause the endotoxin syndrome. The damage mechanism was related to ZO-1which destroyed the tight junction of epithelial cells in intestine mucosa. Ylt could repair ZO-1to decrease permeability of intestine mucosa and protect the intestine mucosal mechanism barrier.
3The heat retention of lung-stomach (intestine) caused the damage of intestine mucosal immune barrier and decreased the slgA level of intestine mucosa. Ylt could make intestine mucosa secrete more slgA and regulate TNF-a, IL-10appropriately, strengthen and balance the partial immunity of intestine mucosa to protect the intestine mucosal immune barrier.
论文共分为理论探讨、文献综述、实验研究三个部分。
第一部分理论探讨
结合中西医相关文献资料,对肺与胃肠相关理论从中医学、西医学以及临床应用三个方面进行探讨和论述。肺与胃肠相关理论源于《黄帝内经》,肺与胃肠经络循行相连,形态结构相近,生理功能相合,并且在气机失调、水液失常、饮食积滞等病理变化上密切相关。随着现代科学技术的发展,肺与胃肠相关理论的现代机理研究更加深入,肺与胃肠在胚胎发育、内分泌调节、黏膜免疫、炎症反应、内毒素损伤、神经调节、气体排泄等方面关系密切。肺与胃肠相关理论一直有效地指导着临床实践,许多呼吸系统常见病,如小儿外感、小儿肺炎、小儿反复呼吸道感染、慢性阻塞性肺病、支气管哮喘等,以及消化系统疾病,如便秘、溃疡性结肠炎、肠易激综合征、胃食管反流病等,利用肺与胃肠同治理论指导治疗,均能够取得较好疗效。
第二部分文献综述
从两个方面进行论述：一、从发病病因、动物模型、现代机理、食积相关肺系热病等方面对小儿食积进行综述,为临床防治食积及食积相关肺系热病奠定理论基础。二、从肠黏膜屏障的组成、生理功能以及肠黏膜屏障功能障碍的损伤机理、中医药治疗等方面进行论述,为探讨银莱汤对动物模型肠黏膜屏障作用机制提供理论依据。
第三部分实验研究
目的：通过建立食积复合病毒性肺炎动物模型,观察动物模型肠黏膜的病理变化,探讨银莱汤对动物模型肠黏膜机械屏障和免疫屏障的作用机制。
方法：通过病因模拟制作肺与胃肠积热动物模型,先予小鼠高蛋白高热量饮食,制作食积模型(阳明胃肠积热证),在此基础上,小鼠乙醚麻醉后经鼻感染流感病毒,制作食积复合病毒性肺炎模型(肺与胃肠积热证)。通过给予银莱汤治疗,观察动物模型的肠黏膜屏障变化情况。实验分为正常组、感染组、食积组、食积感染组、食积治疗组、食积感染治疗组。为研究肠黏膜机械屏障变化,观察小鼠肠组织形态学、肠组织ZO-1水平及血清内毒素水平；为研究肠黏膜免疫屏障变化,观察小鼠肠组织sIgA水平及肠组织细胞因子TNF-a、IL-10水平
结果
肠组织形态学观察：肉眼观察肠黏膜形态,实验各组小鼠肠黏膜结构完整、表面光滑,未见充血、水肿、糜烂、溃疡等病理改变。电子显微镜下观察肠组织切片,正常组与感染组小鼠肠组织结构清晰完整,单层柱状上皮细胞及杯状细胞排列致密整齐,黏膜层无充血、水肿、炎性细胞浸润等病理改变；与正常组比较,食积组与食积感染组小鼠肠组织单层柱状上皮细胞及杯状细胞增大增多,排列紊乱；食积治疗组及食积感染治疗组小鼠肠组织单层柱状上皮细胞、杯状细胞较食积组及食积感染组数量减少、排列整齐。
肠组织ZO-1检测：与正常组比较,食积组与食积感染组小鼠肠组织ZO-1水平显著下降(P<0.01),食积感染治疗组显著升高(P<0.01),感染组与食积治疗组无明显差异(P>0.05)；食积治疗组显著高于食积组(P<0.01)；食积感染治疗组显著高于食积感染组(P<0.01)；食积感染治疗组显著高于食积治疗组(P<0.01)。
血清内毒素检测：与正常组小鼠比较,各组小鼠血清内毒素水平均有不同程度升高,其中食积感染组升高幅度最大,食积治疗组升高幅度最小,但各组之间比较均无显著性差异(P>0.05)。
肠组织sIgA检测：与正常组比较,食积组与食积感染组小鼠的肠组织sIgA水平显著下降(P<0.01),感染组有下降趋势,但无统计学意义(P>0.05)；与感染组比较,食积组显著下降(P<0.01)；经银莱汤治疗后,小鼠肠组织sIgA水平显著升高,食积治疗组显著高于食积组(P<0.01),与正常组比较无显著性差异(P>0.05)；食积感染治疗组显著高于食积感染组(P<0.01),与正常组比较显著升高(P<0.01)；食积感染治疗组sIgA水平显著高于食积治疗组(P<0.01)。
肠组织TNF-a检测：与正常组比较,感染组、食积组及食积感染组小鼠的肠组织TNF-α水平均显著下降(P<0.01),但三组之间比较无显著性差异(P>0.05)；食积治疗组显著高于食积组(P<0.01),但低于正常组水平(P<0.01)；食积感染治疗组显著高于食积感染组(P<0.01),与正常组比较略有升高,但无显著性差异(P>0.05)；食积感染治疗组显著高于食积治疗组(P<0.01)。
肠组织IL-10检测：感染组、食积组及食积感染组小鼠的肠组织IL-10水平与正常组比较均显著下降(P<0.01),三组之间比较无显著性差异(P>0.05)；食积治疗组显著高于食积组(P<0.01)；食积感染治疗组显著高于食积感染组(P<0.01)；食积治疗组及食积感染治疗组与正常组比较无显著性差异(P>0.05),食积治疗组与食积感染治疗组之间比较无显著性差异(P>0.05)。
结论
1肺与胃肠积热状态下,肠黏膜组织形态无明显病理性损伤,但肠黏膜单层柱状上皮细胞及杯状细胞增大增多,排列紊乱,会影响肠黏膜的分泌功能。银莱汤能够降低肠黏膜单层柱状上皮细胞及杯状细胞数量,改善其分布状况,对肠黏膜分泌功能具有调节作用。
2肺与胃肠积热会造成肠黏膜机械屏障的损伤,使肠黏膜的通透性增加,但损伤较轻,不会造成内毒素血症,其损伤机制与肠黏膜上皮细胞间紧密连接蛋白ZO-1的破环有关。银莱汤能够修复肠黏膜ZO-1,从而降低肠黏膜的通透性,对肠黏膜机械屏障具有保护作用。
3肺与胃肠积热会造成肠黏膜免疫屏障的损伤,能够降低肠黏膜sIgA水平,抑制细胞因子TNF-α、IL-10的分泌,从而影响肠黏膜免疫功能。银莱汤能够增加肠黏膜分泌sIgA,适度调节细胞因子TNF-α、IL-10水平,从而增强肠黏膜局部免疫,对肠黏膜免疫屏障具有保护作用。
Yin Lai Tang (Ylt) is an empirical formula of Gu Xiaohong Professor who treats pyretic Lung-Stomach (intestine) syndrome. This formula which is based on the concurrent treatment theory of lung-stomach (intestine), which considers the significant factor of pyretic pulmonary syndrome as retention of heat in stomach and intestine of Yang Ming, attach more importance on purging endogenous heat from Yang Ming. Ylt has a better curative effect on treating pyretic Dyspepsia-Lung syndrome and is used comprehensively in pediatric disease such as infantile cold, infantile pneumonia, puerile recurrent respiratory infection and so on. This study investigates the change of Intestinal mucosal barrier in animal model and makes Ylt's mechanism on intestinal mucosal barrier explicit through building the animal model with infection and dyspepsia. This study provides the reliable experimental evidence on the theory of clinical application of Ylt and has the practical value on prevention and cure of respiratory disease.
The dissertation includes three parts:theoretical discussion, literature review and experimental research.
Part One Theoretical Discussion
The theory of lung-stomach (intestine) correlation was investigated and discussed through Chinese medicine, modern medicine and clinical application according to relevant literature and material in the past dynasties. This theory was from Huangdi Neijing. Thereafter, after more rounded investigation and discussion, the doctors in history found the following viewpoints. The meridians between lung and stomach (intestine) were related. The morphological structure of lung was highly related to stomach. The physiological functions were similar. The pathological changes are highly related in dry-heat impairing syndrome, disorder of qi and body fluid, dyspeptic retention and so on. With the development of modern science and technology, modern mechanism of Lung-stomach (intestine) correlation theory has been investigated further and lung-stomach (intestine) are highly related in embryonic development, endocrine regulation, mucosal immunity, inflammation, viral infect, neuroregulation, gas excretion. The theory of Lung-Stomach (intestine) correlation always provides effective guidance on clinical practice of Chinese medicine. Many diseases were cured effectively based on the theory of treating the disease of Lung-Stomach (intestine) with the same method, including many respiratory diseases, such as infantile cold, infantile pneumonia, puerile recurrent respiratory infection, chronic obstructive pulmonary disease, bronchial asthma, digestive disease such as constipation, ulcerative colitis, irritable bowel syndrome, gastroesophageal reflux disease and so on.
Part Two Literature Review
Two respects have been expounded. One respect:dyspepsia and related febrile diseases in pulmonary system have been discussed and summarized through cause of disease, animal model, and modern mechanism. The other respect:the composition and physiological function of intestine mucosal barrier were expounded as well as the damage mechanism and treatment of Chinese medicine, which provided theoretical evidence for investigating Ylt's mechanism on intestine mucosal barrier of animal model.
Part Three Experimental Research
Purpose:This study investigated the change of Intestinal mucosal barrier in animal model and made Ylt's mechanism on intestinal mucosal barrier explicit through building the animal model with dyspepsia and pneumonia.
Method:Animal model with heat retention was simulated through cause of disease. The mice were feeding food with high calorie to build the animal model with dyspepsia (pyretic Yang Ming Stomach-Intestine syndrome). Then the mice were given flu virus per nasal after etherization to build compound model with viral pneumonia and dyspepsia (pyretic Lung and Stomach intestine syndrome). The changes of intestine mucosal barrier in animal model were observed after the treatment of Ylt. Experiments include normal group, infective group, dyspeptic group, dyspeptic-infective group, dyspeptic and curative group, dyspeptic-infective and curative group. The intestinal histomorphology, ZO-1level of intestinal tissues, serum endotoxin level were observed to study the mechanical changes of intestine mucosal barrier. slgA level and cytokine TNF-a, IL-10level of intestinal tissues were observed to study the immune changes of intestine mucosal barrier.
Result:
Histomorphology of intestine tissue:Through visual observation of intestine mucosal morphous, the structure of the intestine mucosa were integrate and the surface was smooth. Also no pathological change of hyperemia, oedema, erosion, and ulcer occurred. Through observation of intestine tissue slice under an electron microscope the structure of intestine tissue of mice were clear and integrate in both normal and infective group, and simple columnar epithelium cells aligned in good order. Also there were many goblet cells aligning in good order and closely and no pathological change of hyperemia, oedema, inflammation, inflammatory cell infiltration and so on. Simple columnar epithelium cells in dyspeptic group and dyspeptic-infective group aligned in disorder and goblet cells increased and became bigger and align in disorder compared with normal group. In dyspeptic group and curative group, dyspeptic-infective and curative group, goblet cells became bigger. And Simple columnar epithelium cells and goblet cells aligned in disorder but more regularly than in dyspeptic group, dyspeptic-infective group.
ZO-1of intestine tissue:ZO-1level of intestine tissues of the mice significantly decreased (P<0.01) in both dyspeptic group and dyspeptic-infective group compared with normal group, but increased significantly in dyspeptic, infective and curative group (P<0.01). No significant differences were noted in infective group, dyspeptic and curative group (P>0.05). ZO-1level in dyspeptic and curative group was significantly higher than in dyspeptic group (P<0.01). ZO-1level in dyspeptic-infective and curative group was significantly higher than dyspeptic-infective group and dyspeptic group (P<0.01). ZO-1level in dyspeptic-infective and curative group was significantly higher than dyspeptic and curative group.
Serum endotoxin:Serum endotoxin level of each group increased to different extent compared with normal group, of which dyspeptic-infective group increased highest, dyspeptic and curative group increased lowest, but no significant differences were noted in each group.
sIgA of intestine tissue:Compared with normal group, slgA level of intestine tissues in dyspeptic group and dyspeptic-infective group decreased significantly (P<0.01), but no significant differences were noted in infective group(P>0.05). Compared with infective group, slgA level of intestine tissues in dyspeptic group decreased significantly (P<0.01). sIgA level in dyspeptic and curative group was significantly higher than in dyspeptic group (P <0.01), but no significant differences compared with normal group(P>0.05). slgA level in dyspeptic-infective and curative group was significantly higher than dyspeptic-infective group and normal group (P<0.01). slgA level in dyspeptic-infective and curative group was significantly higher than dyspeptic and curative group.
TNF-α of intestine tissue:Compared with normal group, TNF-α level in infective group, dyspeptic group and dyspeptic-infective group decreased significantly (P<0.01) but no significant difference was found in these three group (P>0.05). The data in dyspeptic and curative group was significantly higher than in dyspeptic group (P<0.01) but still lower than in noimal group (P<0.01). The data in dyspeptic-infective and curative group is significantly higher than in dyspeptic-infective group (P<0.01) and compared with normal group, no significant difference was found (P>0.05). The data in dyspeptic-infective and curative group was significantly higher than in dyspeptic and curative group.
IL-10of intestine tissue:IL-10level of intestine tissue in infective group, dyspeptic group and dyspeptic-infective group decreased significantly compared with normal group (P <0.01) and no significant differences was found in these three groups (P>0.05). The data in dyspeptic and curative group was significantly higher than in dyspeptic group. The data in dyspeptic-infective and curative was significantly higher than in dyspeptic-infective group. No significant difference was found in dyspeptic and curative group, dyspeptic-infective and curative group compared with normal group. No significant difference was found between dyspeptic and curative group and dyspeptic-infective and curative group.
Conclusion:
1If there was heat retention in lung, stomach and intestine, the morphous of intestine tissue had no pathological damage. But goblet cells in single columnar epithelium increased and became bigger, aligned in discord, which affected secretion of intestine mucosa. Ylt could improve the number and distribution of goblet cell and regulate the secretion of intestine mucosa.
2The heat retention of lung-stomach (intestine) caused the damage of intestine mucosal mechanism barrier and increased the permeability of intestine mucosa. But the damage was very light and did not cause the endotoxin syndrome. The damage mechanism was related to ZO-1which destroyed the tight junction of epithelial cells in intestine mucosa. Ylt could repair ZO-1to decrease permeability of intestine mucosa and protect the intestine mucosal mechanism barrier.
3The heat retention of lung-stomach (intestine) caused the damage of intestine mucosal immune barrier and decreased the slgA level of intestine mucosa. Ylt could make intestine mucosa secrete more slgA and regulate TNF-a, IL-10appropriately, strengthen and balance the partial immunity of intestine mucosa to protect the intestine mucosal immune barrier.
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