卡托普利抗肝纤维化实验研究

STUDY OF CAPTOPRIL ATTENUATES THE PROGRESSION OF RAT HEPATIC FIBROSIS

目的 :建立大鼠肝纤维化模型 ,探讨卡托普利抗大鼠肝纤维化作用及机制。方法 :Wistar大鼠 4 0只随机分为正常对照组、实验对照组A、实验对照组B、卡托普利预防组、卡托普利治疗组 ,采用混合损害因素构建肝纤维化模型 ;行HE染色和VG胶原染色 ,判断炎症和肝纤维化程度。免疫组化检测各组肝组织TGF - β1、α-SMA的表达。结果 :卡托普利预防组、治疗组的大鼠肝细胞坏死、脂肪变性、炎性细胞漫润及纤维结缔组织增生等较实验对照组明显减轻 ;实验对照组A平均肝纤维化积分值为 2 .17± 0 .75、卡托普利预防组为 1.33±0 .5 2 ;实验对照组B为 2 .86± 0 .6 9、治疗组为 1.6 7± 0 .82 ,两者比较均P <0 .0 5。实验对照组A、卡托普利预防组α-SMA阳性表达细胞数分别为 72± 8.1/视野、31± 5 .5 /视野 ;实验对照组B、治疗组分别为 110± 8.6 /视野、6 7± 4 .3/视野 ,两者比较均P <0 .0 0 1。实验对照组A、卡托普利预防组TGF - β1阳性表达面积比分别为 3.15± 0 .5 3%、2 .2 4± 0 .2 6 % ,两者比较P <0 .0 5 ;实验对照组B、治疗组分别为 4 .77± 0 .4 4 %、3.5 8±0 .4 9% ,两者比较P <0 .0 0 1。各组大鼠肝组织中α -SM阳性细胞数与TGF - β1阳性表达面积比呈正相关 (r=0 .86 7,P =0 .0 0 7)。结论 :各组大鼠?

Objective:To investigate the effects of captopnl on rat hepatic fibrosis and explore the underlying mechanism by establishing hepatic fibrosis models.Methods:Forty healthy Wistar rats were randomly divided into five groups: normal control group, experimental group A, exprimental group B, captopril-prevented grOuP, captopril-treated group. Hepatic fibrosis models were established in the latter 4 groups by combining factor. Liver sections were stained by hemafoxylin-eosm and Van Gieson to evaluate the degree of inflammation and hepatic fibrosis. Expression of TGF-β 1, α-SMA in liver were assayed by immunohistochemistry.Results:Compared with experimental group A and B respectively, the hepatoceUular necrosis, fatty degeneration, inflammation and fibrosis of captopril-prevented group and treatment group was slighter.There was significant difference between captopril-prevented group (1.33±0.52) and experiment group A (2.17±0.75 ) on histologic assessment of hepatic fibrosis; And it was the same with captopril-treated group (1.67±0.82) and experiment group B (2.86+0.69) , P < 0.05 . Much more α-SMA positive cells,distributing in portal vessels, hepatic smusoid and the areas where collagen deposited,were seen m experimental group A and B (72±8.1 and 110±8.6,respeclively) .Expression of α-SMA in captopril-prevented group and treatment group (31±5.5 and 67±4.3,respectively) was weaker than experimental group A and B, P <0.001. Much more TGF-β 1 ,dis tributing in interstitial and the areas where collagen deposited ,were seen in experimental group A and B (3.15±0.53% and 4.77± 0.44%,respectively). Expression of TGF-β 1 in captopril-prevented group and treatment group(2.24±0.26% and 3.58±0.49%, respectively) was weaker than in experimental group A and B, P <0.05 and P <0.001, respeetively.Expression of α-SMA and TGF-β 1 showed a positive correlation with each other. (r=0.867, P =0.007).Conclusion: Expression of α-SMA and TGF-β1 showed apositive correlation with each other. Captopril could suppress expression of TGF-β 1 and activation and proliferation of α-SMA.