CAJ | 학술논문

目的：探讨丹酚酸B对非酒精性脂肪性肝炎（NASH）大鼠肝细胞凋亡的影响及对NASH的治疗作用。方法清洁级雄性SD大鼠60只，随机分为对照组、NASH模型组、丹酚酸B治疗组，每组20只。对照组以普通饲料喂养，其余2组以高脂饲料连续喂养12周复制NASH模型。第13周开始治疗组每天以浓度为1 mg／ml的丹酚酸B溶液20 ml／kg灌胃，模型组以20 ml／kg蒸馏水灌胃。治疗12周后，处死大鼠，取血及肝组织，计算肝指数，检测血清ALT、AST、甘油三酯（TG）、总胆固醇（TC），观察肝组织病理学变化，免疫组织化学法检测肝组织细胞色素C（CytC）、caspase－3蛋白的表达，逆转录－聚合酶链反应（RT－PCR）检测肝组织p53、Bax、Bcl－2 mRNA的表达。结果模型组大鼠肝指数、ALT、AST、TG、TC较对照组增高，肝组织炎症明显；CytC及caspase－3蛋白表达增加（P值均＜0．01）；Bcl－2 mRNA表达降低，p53、Bax mRNA表达增高（P值均＜0．01）。治疗组与模型组相比肝指数、ALT、AST、TG、TC降低，炎症减轻；CytC及caspase－3蛋白表达减少（P值均＜0．01）；Bcl－2 mRNA表达升高（P＜0．05），p53 mRNA表达降低（P＜0．05），Bax mRNA 表达降低（P＜0．01）。结论丹酚酸 B 可通过调节 Bcl －2、p53、Bax mRNA 表达，降低 CytC 及caspase－3蛋白的表达，抑制肝细胞凋亡，对NASH起治疗作用。
목적：탐토단분산B대비주정성지방성간염（NASH）대서간세포조망적영향급대NASH적치료작용。방법청길급웅성SD대서60지，수궤분위대조조、NASH모형조、단분산B치료조，매조20지。대조조이보통사료위양，기여2조이고지사료련속위양12주복제NASH모형。제13주개시치료조매천이농도위1 mg／ml적단분산B용액20 ml／kg관위，모형조이20 ml／kg증류수관위。치료12주후，처사대서，취혈급간조직，계산간지수，검측혈청ALT、AST、감유삼지（TG）、총담고순（TC），관찰간조직병이학변화，면역조직화학법검측간조직세포색소C（CytC）、caspase－3단백적표체，역전록－취합매련반응（RT－PCR）검측간조직p53、Bax、Bcl－2 mRNA적표체。결과모형조대서간지수、ALT、AST、TG、TC교대조조증고，간조직염증명현；CytC급caspase－3단백표체증가（P치균＜0．01）；Bcl－2 mRNA표체강저，p53、Bax mRNA표체증고（P치균＜0．01）。치료조여모형조상비간지수、ALT、AST、TG、TC강저，염증감경；CytC급caspase－3단백표체감소（P치균＜0．01）；Bcl－2 mRNA표체승고（P＜0．05），p53 mRNA표체강저（P＜0．05），Bax mRNA 표체강저（P＜0．01）。결론단분산 B 가통과조절 Bcl －2、p53、Bax mRNA 표체，강저 CytC 급caspase－3단백적표체，억제간세포조망，대NASH기치료작용。
Objective To investigate the effect of salvianolic acid B on hepatocyte apoptosis in rats with nonalcoholic steatohepatitis (NASH)and the efficacy of salvianolic acid B in the treatment of NASH.Methods Sixty clean male SD rats were randomly divided into control group,NASH model group,and salvianolic acid B treatment group,with 20 rats in each group.The control group was fed with normal diet,while the other two groups with high-fat diet for 12 continuous weeks to establish a NASH model.From week 13,rats in the treatment group were gavaged with 1 mg/ml salvianolic acid B (20 ml/kg b.w.daily);while the model group with distilled water (20 ml/kg b.w dai-ly).After 12 weeks of treatment,the rats were sacrificed;blood and hepatic tissues were sampled,liver index (liver weight/body weight) calculated,serum levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),triglycerides (TG),and total cholesterol (TC)measured,and the pathologic changes in hepatic tissues observed.The protein expression of caspase-3 and cytochrome C (CytC)in hepatic tissues was measured by immunohistochemical methods.The mRNA expression of p53,Bax,and Bcl -2 in hepatic tissues was measured by RT-PCR.Results Compared with the normal group,the model group showed higher liver index and serum levels of ALT, AST,TG,and TC and more obvious inflammation of hepatic tissues;the protein expression of CytC and caspase -3 was significantly in-creased (P<0.01 for both);the mRNA expression of Bcl-2 was significantly reduced (P<0.01),while that of Bax and p53 was signifi-cantly increased (P<0.01 for both).Compared with the model group,the treatment group showed alleviated inflammation and reduced liver index and serum levels of ALT,AST,TG,and TC;the protein expression of CytC and caspase-3 was significantly reduced (P<0.01 for both);Bcl-2 mRNA expression was significantly increased (P<0.05 ),p53 mRNA expression significantly reduced (P<0.05 ),and Bax mRNA expression also significantly reduced (P<0.01 ).Conclusion Salvianolic acid B can inhibit hepatocyte apoptosis and treat NASH by regulating the mRNA expression of Bcl-2,p53,and Bax and reducing the protein expression of CytC and caspase-3.