CAJ | 학술논문

目的：探讨卡维地洛抑制肝纤维化的效果及机制。方法将36只雄性SD大鼠随机分为对照组6只、模型组10只、治疗1组及治疗2组各10只。模型组和治疗组采用胆总管结扎法建立大鼠肝纤维化模型。治疗1、2组造模成功后48 h开始每天予卡维地洛药液1 mg／kg分2次灌胃，分别用药2、4周；对照组及模型组同时灌等量蒸馏水。实验结束后取各组大鼠肝左叶组织切片，行常规HE染色和Masson三色染色，光镜下观察各组肝脏纤维化情况；Western blot法检测各组肝组织瘦素以及瘦素受体表达；Real-time Q-PCR法检测瘦素及瘦素受体mRNA。结果 HE及Masson三色染色光镜下观察可见，模型组成功建立胆汁淤积性肝纤维化模型，随着造模时间延长肝纤维化程度逐渐加重。治疗1、2组肝脏纤维化程度较模型组减轻，肝脏纤维化分期降低，P＜0．05。治疗2组肝纤维化程度与治疗1组无统计学差异（P＞0．05）。模型组肝组织瘦素、瘦素受体蛋白及mRNA表达量均较对照组升高（P均＜0．05），治疗1、2组肝组织瘦素、瘦素受体蛋白及mRNA表达量均较模型组降低（P均＜0．05），两治疗组相比无统计学差异（P＞0．05）。结论卡维地洛能对肝纤维化有抑制作用；其机制可能为下调瘦素及瘦素受体基因表达。
목적：탐토잡유지락억제간섬유화적효과급궤제。방법장36지웅성SD대서수궤분위대조조6지、모형조10지、치료1조급치료2조각10지。모형조화치료조채용담총관결찰법건립대서간섬유화모형。치료1、2조조모성공후48 h개시매천여잡유지락약액1 mg／kg분2차관위，분별용약2、4주；대조조급모형조동시관등량증류수。실험결속후취각조대서간좌협조직절편，행상규HE염색화Masson삼색염색，광경하관찰각조간장섬유화정황；Western blot법검측각조간조직수소이급수소수체표체；Real-time Q-PCR법검측수소급수소수체mRNA。결과 HE급Masson삼색염색광경하관찰가견，모형조성공건립담즙어적성간섬유화모형，수착조모시간연장간섬유화정도축점가중。치료1、2조간장섬유화정도교모형조감경，간장섬유화분기강저，P＜0．05。치료2조간섬유화정도여치료1조무통계학차이（P＞0．05）。모형조간조직수소、수소수체단백급mRNA표체량균교대조조승고（P균＜0．05），치료1、2조간조직수소、수소수체단백급mRNA표체량균교모형조강저（P균＜0．05），량치료조상비무통계학차이（P＞0．05）。결론잡유지락능대간섬유화유억제작용；기궤제가능위하조수소급수소수체기인표체。
Objective To investigate the effect and mechanism of carvedilol on inhibition of liver fibrosis.Methods Thirty-six male SD rats were randomly divided into groups:the control group (n=6), model group (n=10), the carve-diloltreatment group 1 (n =10) and the carvedilol treatment group 2 (n =10).Liver fibrosis rat models were establishedthrough common bile duct ligation.After the models were accomplished for 48 hours, the rats of treatment groups 1 and 2were gavaged with carvedilol 1 mg/kg twice a day for 2 weeks and 4 weeks.The rats in the control group and model groupwere gavaged with equal quantity distilled water at the same time.After the experiments, liver tissue sections were preparedfrom left lobe of liver, routine HE staining and Masson trichrome staining were used to observe the liver fibrosis in eachgroup.The expression of leptin and soluble leptin receptor (sOB-R) in the liver tissues of each group was detected byWestern blotting, and the mRNA expression of leptin and leptin receptor was detected with real-time Q-PCR.Results HEand Masson trichrome showed, cholestatic liver fibrosis rat model was successfully established.The degree of liver fibrosisaggravated gradually as the molding time extension.The liver fibrosis in the carvedilol treatment group 1 and group 2 wasdecreased significantly as compared with that of the model group, and the pathological stage of liver fibrosis reduced significantlyas compared with that of the model group (P <0.05).No statistically significant difference was found between treatmentgroup 1 and treatment group 2 (P >0.05).The protein and mRNA expression of leptin and sOB-R in the rat liver tissuesof the model group was significantly higher than that of the control group (all P <0.05).The protein and mRNA expressionof leptin and sOB-R in the rat liver tissues of the carvedilol treatment groups 1 and 2 was significantly decreased ascompared with that of the model group (all P <0.05), but the differences between treatment group 1 and treatment group2 was not statistically significant (P >0.05).Conclusion Carvedilol can inhibit the process of liver fibrosis, whosemechanism may be the down-regulation of the expression of leptin and sOB-R in the liver tissues.