局部应用地塞米松预防兔移植静脉再狭窄的实验研究
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摘要
目的:观察局部应用地塞米松对新西兰兔自体移植静脉再狭窄的影响,并探讨其可能作用机制。
方法:新西兰兔30只,建立兔自体颈外静脉一颈总动脉移植模型,随机分为三组:A组为空白对照组;B组为生物蛋白胶组;C组为地塞米松组,各组动物分别于术后第3周取移植静脉标本,标本病理切片行HE染色测量内膜、中膜厚度及管壁炎性细胞数,免疫组化检测PCNA(周期蛋白)阳性细胞率、TUNEL法检测凋亡细胞阳性率。
结果:
1.大体观察
对照组和实验组新西兰兔均全部存活,切口愈合良好,无感染渗液,取材时见移植术后纤维蛋白胶已被吸收,组织结构层次清楚,血管与周围组织无粘连,吻合段血管未变细,血管吻合口通畅,静脉搏动良好,无血管瘤及血管闭塞形成。
2.组织形态
HE染色显示术后三组动物移植静脉内膜均可见增厚,术后3周,地塞米松组较生物蛋白胶组、空白对照组均明显降低内膜、中膜增生厚度(p﹤0.05),炎性细胞数减少(p﹤0.05);生物蛋白胶组较空白对照组也抑制内膜、中膜厚度增生(p﹤0.05),但炎性细胞数无显著差异(p﹥0.05)。
3.移植静脉PCNA免疫组化染色
术后3周,地塞米松组移植静脉PCNA阳性细胞百分比为(24.91±1.51)%,较生物蛋白胶组百分数(39.14±1.74)%及空白对照组(41.37±2.41)明显减少(p﹤0.05);生物蛋白胶组较空白对照组PCNA的表达降低(p﹤0.05)。
4.TUNEL法测定细胞原位凋亡
术后3周,地塞米松组移植静脉TUNEL细胞凋亡百分比为(20.68±1.45)%,较生物蛋白胶组(18.83±0.74)%及空白对照组(15.33±1.56)明显增加(p﹤0.05);生物蛋白胶组较空白对照组增加细胞凋亡阳性率(p﹤0.05)。
结论:
1.地塞米松在新西兰兔自体静脉移植中能通过抑制局部炎症反应,抑制平滑肌细胞增殖、促使血管平滑肌细胞凋亡,从而防止移植静脉再狭窄。
2.生物蛋白胶不但能作为一种药物的携载体,还能抑制血管平滑肌细胞增殖,促使其凋亡,防止移植血管再狭窄。
Objective:
To observation influence of application dexamethasone on the New Zealand rabbit autologous vein graft restenosis and to explore its mechanism.
Methods:
The establish ment of autografted venous model was used with external jugularvein-arteria carotis transplantation in New Zealand rabbit. According to the administration condition after autografted venous transPlantation,30 New Zealand rabbits were randomly classified into three groups: (A) Blank control group (B) fibrin group (C) dexamethasone group. At 3 week after transPlantation, the vein grafts were harvested. The grafts were stained with HE to observe the thickness of the intima and Lymphocyte number ,were stained with proliferating cell nuclear antigen(PCNA) to study the proliferation of the wall cells.The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL) method was used to detect in situ apoptosis.
Results:
1.Macroscopic observation:All the experimental animals survived when the experiment completed.The patency rate of the vein grafts was 100%and there was no rupture of the vein grafts until they were harvested. The fibrin glue has been absorbed, the organizational structure level is clear, the blood vessel and the peritonsillar tissue do not have the adhesion, the vein putsation is good, does not have angioma and the vascular occlusion formation when the vein grafts were harvested.
2.Morphology: Three weeks after the transplantation,HE staining showed that the the thickness of the intima and Lymphocyte number of the Group C is less than Group A and Group B(p﹤0.05). the the thickness of the intima of Group B is less than Group A,but lymphocyte number not remarkable difference(p﹥0.05).
3.Immunohistochemistry of PCNA:Three weeks after the transplantation,there were less PCNA positive cells in the intima in Group C(24.91%±1.51%) than Group A(41.37%±2.41%) or Group B(39.14%±1.74%) . The percent of PCNA positive cells in the intima of the Group A was more than Group B(P<0.05).
4. The detect of cell apoptosis in situ by TUNEL:The percentage of TUNEL positive cells in Group C(20.68%±1.45%)is more than Group A(15.33%±1.56%) or Group B(18.83%±0.74%) (P<0.05)in the three weeks after operation. The percentage of TUNEL positive cells in Group B) is more than Group A (P<0.05).
Conclusions:
1.Dexamethasone can reduce the expression of PCNA in vein vascular smooth muscle in the autogenous graft, enhance the expression of TUNEL in vein vascular smooth muscle in the autogenous graft, thus Prevention transplant vein again narrow.
2.The fibrin glue as a very good medicine also have well prevents the vein graft to be restenosis.
方法:新西兰兔30只,建立兔自体颈外静脉一颈总动脉移植模型,随机分为三组:A组为空白对照组;B组为生物蛋白胶组;C组为地塞米松组,各组动物分别于术后第3周取移植静脉标本,标本病理切片行HE染色测量内膜、中膜厚度及管壁炎性细胞数,免疫组化检测PCNA(周期蛋白)阳性细胞率、TUNEL法检测凋亡细胞阳性率。
结果:
1.大体观察
对照组和实验组新西兰兔均全部存活,切口愈合良好,无感染渗液,取材时见移植术后纤维蛋白胶已被吸收,组织结构层次清楚,血管与周围组织无粘连,吻合段血管未变细,血管吻合口通畅,静脉搏动良好,无血管瘤及血管闭塞形成。
2.组织形态
HE染色显示术后三组动物移植静脉内膜均可见增厚,术后3周,地塞米松组较生物蛋白胶组、空白对照组均明显降低内膜、中膜增生厚度(p﹤0.05),炎性细胞数减少(p﹤0.05);生物蛋白胶组较空白对照组也抑制内膜、中膜厚度增生(p﹤0.05),但炎性细胞数无显著差异(p﹥0.05)。
3.移植静脉PCNA免疫组化染色
术后3周,地塞米松组移植静脉PCNA阳性细胞百分比为(24.91±1.51)%,较生物蛋白胶组百分数(39.14±1.74)%及空白对照组(41.37±2.41)明显减少(p﹤0.05);生物蛋白胶组较空白对照组PCNA的表达降低(p﹤0.05)。
4.TUNEL法测定细胞原位凋亡
术后3周,地塞米松组移植静脉TUNEL细胞凋亡百分比为(20.68±1.45)%,较生物蛋白胶组(18.83±0.74)%及空白对照组(15.33±1.56)明显增加(p﹤0.05);生物蛋白胶组较空白对照组增加细胞凋亡阳性率(p﹤0.05)。
结论:
1.地塞米松在新西兰兔自体静脉移植中能通过抑制局部炎症反应,抑制平滑肌细胞增殖、促使血管平滑肌细胞凋亡,从而防止移植静脉再狭窄。
2.生物蛋白胶不但能作为一种药物的携载体,还能抑制血管平滑肌细胞增殖,促使其凋亡,防止移植血管再狭窄。
Objective:
To observation influence of application dexamethasone on the New Zealand rabbit autologous vein graft restenosis and to explore its mechanism.
Methods:
The establish ment of autografted venous model was used with external jugularvein-arteria carotis transplantation in New Zealand rabbit. According to the administration condition after autografted venous transPlantation,30 New Zealand rabbits were randomly classified into three groups: (A) Blank control group (B) fibrin group (C) dexamethasone group. At 3 week after transPlantation, the vein grafts were harvested. The grafts were stained with HE to observe the thickness of the intima and Lymphocyte number ,were stained with proliferating cell nuclear antigen(PCNA) to study the proliferation of the wall cells.The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL) method was used to detect in situ apoptosis.
Results:
1.Macroscopic observation:All the experimental animals survived when the experiment completed.The patency rate of the vein grafts was 100%and there was no rupture of the vein grafts until they were harvested. The fibrin glue has been absorbed, the organizational structure level is clear, the blood vessel and the peritonsillar tissue do not have the adhesion, the vein putsation is good, does not have angioma and the vascular occlusion formation when the vein grafts were harvested.
2.Morphology: Three weeks after the transplantation,HE staining showed that the the thickness of the intima and Lymphocyte number of the Group C is less than Group A and Group B(p﹤0.05). the the thickness of the intima of Group B is less than Group A,but lymphocyte number not remarkable difference(p﹥0.05).
3.Immunohistochemistry of PCNA:Three weeks after the transplantation,there were less PCNA positive cells in the intima in Group C(24.91%±1.51%) than Group A(41.37%±2.41%) or Group B(39.14%±1.74%) . The percent of PCNA positive cells in the intima of the Group A was more than Group B(P<0.05).
4. The detect of cell apoptosis in situ by TUNEL:The percentage of TUNEL positive cells in Group C(20.68%±1.45%)is more than Group A(15.33%±1.56%) or Group B(18.83%±0.74%) (P<0.05)in the three weeks after operation. The percentage of TUNEL positive cells in Group B) is more than Group A (P<0.05).
Conclusions:
1.Dexamethasone can reduce the expression of PCNA in vein vascular smooth muscle in the autogenous graft, enhance the expression of TUNEL in vein vascular smooth muscle in the autogenous graft, thus Prevention transplant vein again narrow.
2.The fibrin glue as a very good medicine also have well prevents the vein graft to be restenosis.
引文
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[1]陈鑫.冠状动脉搭桥术治疗冠心病的现状和进展[J].实用临床医药杂志,2005,9(3) :3 - 8.
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[5]Parolari A, Mussoni L, Frigerio M, etal. Increased prothrombot-ic state lasting as long as one month after on-pump and off-pump coronary surgery. J Thorac Cardiovasc Surg,2005,130:303-308.
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[18]Pep ine CJ,Hirshfeld JW,Macdonald RG,et al.A contr olled trial of corticosteer oids t o p revent restenosis after cor onary angi op lasty[J]. Circulati on,1990,81(6) : 1753- 1761 .
[19] MacDonald RG,Panush RS,Pepine CJ.Rationale for use of glueacortioids in modification of restenosis after percutaneous transluminal coronary angioplasty [J].Am J Cardiol,1987,60(3):56B-60B.
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[22]冯克福,严激.冠状动脉支架术与炎症反应[J].心血管病学进展,2008,29(5):11-13.
[23] BerkB, Rao GN.Angiotension II induced vascular smooth muscle cell hypertrophy:PDGF-A chain mediaes increase in cell size.[J]cell Physiol, 1993 ,154 :368-380.
[24] Lee S , Tsou A , Chan H , et al . G lucocorticoids selectively inhibit the transcription of interleukin 1b gene and decrease the stability of interleukin 1b mRNA. Proc Natl Acad Sci USA , 1988 ,85 :1204-1208.
[25] Lafont A , Guzman L , G oormastic M, C ornhill J , et al . Restenosis after experimental angioplasty : intimal , medial , and adventitial changes associated with consrictive remodeling, Circ Res , 1995 ,76 :996-1002.
[26]王建波,杨建勇,陈伟,等.炎症在内支架植入术后再狭窄中的作用及地塞米松干预的实验研究[J].临床放射学杂志,2006 25(6):566-570.
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[29] Gaspasdone A,Versaei F,Preietti I,et a1.Efect of atorvastatin(8O mg)initiated at the time of coronary artery stent implantation on C-reactive protein and six-month clinical events[J].Am J Cardiol,2002,90(7):786-789
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[31] Sacks FM, PfefferMA,Moye LA, et al. The effect of p ravastatin on coronary events after myocardial infarction in patientswith average cholesterol levels [ J ].N Engl J Med, 1996, 335: 1001-1009.
[32]Furukawa Y,Matsumori A,Ohashi N.Anti-monocyte chemoattractant protein-1/monocyte chemotactic and activating factor antibody inhibitsneointima-l hyperplasia in injured rat carotid arteries[J].Cire Res,1999.84:306-314.
[33]Egashira K.Zhao Q,Kataoka C,et a1.importanee of monocyte chemoattractant protein-1 pathway in neointimal hyperplasia after periarterial iniury in mice and monkeys [J].Circ Res,2002,90(11):1167-1172.
[34]Cable DG,O’brien T,Capllce N.The role of gene therapy for infimal hyperplasia of bypass graft[J].Circulation,1999,100(Suppl 19):392-396.
[35]Qiang BP,SegevA,BeliardI,eta1.Poly(methylidene malonate 2.1.2)nanopartieles: a biocompatible polymer that enhances pefi-Adventitial adenoviral gene delivery[J].J Control Release,2004,98:47-455.
[36]Li JJ, Qin XW, Yang XC,et al.Randomized comparis on of earely inflammat oryresponse after siroli museeluting stentvs bare meteal stentimp lantation in native coronary lesions.Clin Chim Acta,2008,396:38- 42.