CAJ | 학술논문

目的：观察阻断肾素—血管紧张素—醛固酮系统（ RAAS）不同环节对实验性肝纤维化大鼠肝组织纤维化程度的影响并探讨其作用机制。方法取6周龄SD大鼠50只，随机分为正常对照组、模型组、卡托普利组、氯沙坦组和螺内酯组各10只。正常对照组皮下注射橄榄油，其他组给予40％ CCL4腹壁皮下注射制备肝纤维化模型；自次日起，卡托普利组、氯沙坦组、螺内酯组分别经胃管内灌注ACE抑制剂卡托普利、血管紧张素（ Ang）Ⅱ的Ⅰ型受体阻断剂氯沙坦、醛固酮受体拮抗剂螺内酯，模型组和正常对照组灌注等量生理盐水。各组动物均于第8周处死，取肝组织行HE染色和Masson染色，观察其病理变化。 ELISA法测定血清与肝组织中ACE2、AngⅡ、Ang 1-7。结果卡托普利组、氯沙坦组和螺内酯组肝纤维化程度较模型组明显好转；模型组、卡托普利组、氯沙坦组、螺内酯组的血清及肝组织中ACE2、AngⅡ、Ang 1-7水平均高于正常对照组，卡托普利组、氯沙坦组、螺内酯组的ACE2及Ang 1-7水平均高于模型组、AngⅡ水平低于模型组（ P均＜0．05）；氯沙坦组、螺内酯组的ACE2、AngⅡ、Ang 1-7水平与卡托普利组相比差异无统计学意义。结论阻断RAAS不同环节均可抑制肝纤维化形成，其机制可能是通过升高血清及肝组织中ACE2、Ang 1-7水平、降低AngⅡ水平来发挥抗肝纤维化的作用。
목적：관찰조단신소—혈관긴장소—철고동계통（ RAAS）불동배절대실험성간섬유화대서간조직섬유화정도적영향병탐토기작용궤제。방법취6주령SD대서50지，수궤분위정상대조조、모형조、잡탁보리조、록사탄조화라내지조각10지。정상대조조피하주사감람유，기타조급여40％ CCL4복벽피하주사제비간섬유화모형；자차일기，잡탁보리조、록사탄조、라내지조분별경위관내관주ACE억제제잡탁보리、혈관긴장소（ Ang）Ⅱ적Ⅰ형수체조단제록사탄、철고동수체길항제라내지，모형조화정상대조조관주등량생리염수。각조동물균우제8주처사，취간조직행HE염색화Masson염색，관찰기병리변화。 ELISA법측정혈청여간조직중ACE2、AngⅡ、Ang 1-7。결과잡탁보리조、록사탄조화라내지조간섬유화정도교모형조명현호전；모형조、잡탁보리조、록사탄조、라내지조적혈청급간조직중ACE2、AngⅡ、Ang 1-7수평균고우정상대조조，잡탁보리조、록사탄조、라내지조적ACE2급Ang 1-7수평균고우모형조、AngⅡ수평저우모형조（ P균＜0．05）；록사탄조、라내지조적ACE2、AngⅡ、Ang 1-7수평여잡탁보리조상비차이무통계학의의。결론조단RAAS불동배절균가억제간섬유화형성，기궤제가능시통과승고혈청급간조직중ACE2、Ang 1-7수평、강저AngⅡ수평래발휘항간섬유화적작용。
Objective To observe the effects of local blockage of renin-angiotensin-aldosterone system ( RAAS) on the degrees of fibrosis and to investigate its mechanism in liver tissues of experimental rats with hepatic fibrosis .Methods Fifty SD rats aged 6 weeks were randomly divided into five groups: the normal control group , model group , captopril group, losartan group and spironolactone group , with 10 rats in each group .In the normal control group , the rats received subcutaneous injection of olive oil , while other rats received subcutaneous injection of 40%CCL4 to make the hepatic fibro-sis models.The next day, rats of the three treatment groups were daily injected with captopril (captopril group), losartan ( losartan group ) and spironolactone ( spironolactone group ) .Rats in the control group and model group received the same amount of normal saline everyday .Rats in each group were sacrificed at 8 weeks.The liver tissues were obtained and stained by HE staining and Masson staining to observe the pathological changes .Enzyme-linked immunosorbent assay ( ELISA) was used to determine the levels of ACE 2, AngⅡand Ang 1-7 in the serum and liver tissues .Results The de-gree of liver fibrosis in the captopril group , losartan group and spironolactone group was significantly improved as compared with that of the model group;the levels of ACE2, AngⅡ, Ang 1-7 in the serum and liver tissue of the model group , capto-pril group, losartan group and spironolactone group were all higher than those of the normal control group ; the levels of ACE2 and Ang 1-7 in the captopril group , losartan group and spironolactone group were all higher , but the Ang Ⅱ level was lower than that of the model group (all P<0.05).No statistically significant differences were found in the levels of ACE2, Ang Ⅱ, and Ang 1-7 between the losartan group , spironolactone group and captopril group .Conclusion The lo-cal blockage of RAAS at different levels may all inhibit the liver fibrosis , whose mechanism may be related with the increase of ACE2 and Ang 1-7 and the decrease of AngⅡin the serum and liver tissues .