CAJ | 학술논문

目的：研究大麻素受体1（CB1）拮抗剂利莫那班对肝纤维化模型C57小鼠肝组织中CB1、α-平滑肌肌动蛋白（α-SMA）表达的影响，及其抗肝纤维化的作用机制。方法30只C57小鼠随机分为3组，分别为正常对照组、模型对照组及利莫那班组，每组10只。采用四氯化碳腹腔注射诱导形成小鼠肝纤维化模型。造模2周后于继续造模同时，正常对照组和模型对照组每天生理盐水灌胃，利莫那班组用利莫那班灌胃。第8周造模结束时处死小鼠，留取肝脏组织标本，分别进行HE和Masson三色染色，应用免疫组织化学方法检测肝组织中CB1和α-SMA的表达，并进行肝组织纤维化评分(S评分)。结果模型对照组和利莫那班组肝组织S评分、CB1和α-SMA阳性表达量均高于正常对照组（均P<0.05），利莫那班组均低于模型对照组（均P<0.05）；正常对照组、模型对照组和利莫那班组CB1评分、α-SMA评分与S评分相互之间均呈正相关（均P<0.05）。结论肝组织CB1的激活可促进肝纤维化的形成， CB1拮抗剂利莫那班通过抑制CB1表达，进而抑制肝星状细胞的增殖和激活，从而起到抗肝纤维化的作用。
목적：연구대마소수체1（CB1）길항제리막나반대간섬유화모형C57소서간조직중CB1、α-평활기기동단백（α-SMA）표체적영향，급기항간섬유화적작용궤제。방법30지C57소서수궤분위3조，분별위정상대조조、모형대조조급리막나반조，매조10지。채용사록화탄복강주사유도형성소서간섬유화모형。조모2주후우계속조모동시，정상대조조화모형대조조매천생리염수관위，리막나반조용리막나반관위。제8주조모결속시처사소서，류취간장조직표본，분별진행HE화Masson삼색염색，응용면역조직화학방법검측간조직중CB1화α-SMA적표체，병진행간조직섬유화평분(S평분)。결과모형대조조화리막나반조간조직S평분、CB1화α-SMA양성표체량균고우정상대조조（균P<0.05），리막나반조균저우모형대조조（균P<0.05）；정상대조조、모형대조조화리막나반조CB1평분、α-SMA평분여S평분상호지간균정정상관（균P<0.05）。결론간조직CB1적격활가촉진간섬유화적형성， CB1길항제리막나반통과억제CB1표체，진이억제간성상세포적증식화격활，종이기도항간섬유화적작용。
Objective To study the effect of rimonabant, cannabinoid receptor 1(CB1) antagonist, on the expressions of CB1 andα-smooth muscle actin (α-SMA) in C57 mice with experimental hepatic fibrosis, and their mechanisms in liver fibrosis progression thereof. Methods Thirty C57 mice were randomly divided into three groups, normal control group, mod-el control group and model+rimonabant group, 10 mice for each group. The mouse model of experimental hepatic fibrosis was induced by intraperitoneal injection with 10%CCl4 for two weeks. The normal saline was delivered by gavage daily in normal control group and model control group. Rimonabant was given to mice in model+rimonabant group. Mice were sacri-ficed at the end of eight weeks. Samples of liver tissue were collected. The expressions of CB1 andα-SMA in liver tissue of mice were observed by immunohistochemical staining. The score of fibrosis stage (S) in liver tissue was also analyzed. Re-sults The positive expressions of CB1 andα-SMA and the score S were significantly higher in model control group and model+rimonabant group than those in normal control group (P<0.05). The positive expressions of CB1 andα-SMA and the score S were significantly lower in rimonabant group than those in model control group (P<0.05). There were positive corre-lations in CB1,α-SMA and S scores between normal control group, model control group and model+rimonabant group (P<0.05). Conclusion The activation of CB1 can promote the formation of liver fibrosis. The anti-fibrotic effect of rimonabant, CB1 antagonist, related with the inhibiting of the proliferation and activation of hepatic stellate cells (HSC), and the inhibit-ing of the expression of CB1.