双蓣调脂汤对高胆固醇血症模型大鼠肝组织中HMGCR、ABCG5及ABCG8表达的影响

目的探讨双蓣调脂汤治疗高胆固醇血症的可能作用机制。方法32只雄性SD大鼠随机分为对照组、模型组、双蓣调脂汤组和辛伐他汀组,每组8只。除正常组给予普通饲料外,其余各组大鼠均给予高脂饲料喂养4周建立高胆固醇血症模型。双蓣调脂汤组给予双蓣调脂汤7.8 g/(kg·d)灌胃,辛伐他汀组给予辛伐他汀混悬液4 mg/(kg·d)灌胃,对照组和模型组给予等量生理盐水灌胃,每组均连续灌胃4周或8周,HE染色法观察大鼠肝组织病理变化,测定各组大鼠血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平,并采用荧光定量PCR、Western Blot、免疫组化法检测肝组织中3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)、三磷酸腺苷结合盒G5(ABCG5)和三磷酸腺苷结合盒G8(ABCG8)mRNA或蛋白表达。结果与对照组相比,模型组大鼠肝组织出现明显的脂肪变性,TC、TG及LDL-C水平均显著升高(P<0.01),肝组织中HMGCR、ABCG5和ABCG8表达升高;与模型组比较,双蓣调脂汤组肝脏脂肪变性明显减轻,TC、TG及LDL-C均明显降低(P<0.05),肝组织中HMGCR mRNA及蛋白水平显著降低(P<0.01),而ABCG5 mRNA和ABCG8 mRNA及蛋白水平显著升高(P<0.01),并且双蓣调脂汤灌胃8周比4周作用更显著(P<0.01)。结论双蓣调脂汤能减轻肝脏脂肪变性,降低高胆固醇血症大鼠血脂,其机制可能与下调HMGCR表达,同时上调ABCG5和ABCG8表达有关。

Effect of Shuangyu Tiaozhi Decoction on Expressions of Hepatic HMGCR,ABCG5 and ABCG8 in Hypercholesterolemic Rat Model

Objective To investigate the possible mechanism of Shuangyu Tiaozhi Decoction in the treatment of hypercholesterolemia.Methods Thirty-two male SD rats were randomly divided into control group,model group,Shuangyu Tiaozhi Decoction group and simvastatin group,with 8 rats in each.Except for the control group,the remaining groups’rats were fed with high-cholesterol diet for 4 weeks to establish a hypercholesterolemia model.The Shuangyu Tiaozhi Decoction group was given Shuangyu Tiaozhi Decoction 7.8 g/(kg·d)for gavage.The simvastatin group was given simvastatin suspension 4 mg/(kg·d)for gavage.The control group and model group were given the equal dose of normal saline for gavage.Each group was continuously perfused for 4 or 8 weeks.The histopathological changes of rat liver tissue were observed by using H-E staining.The serum total cholesterol(TC),triglyceride(TG),low density lipoprotein-cholesterol(LDL-C)and high density lipoprotein-cholesterol(HDL-C)levels were measured.The real-time PCR,Western-Blot and immunohistochemistry were used to detect mRNA or protein levels of 3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR),ATP Binding Cassette G5(ABCG5)and ATP Binding Cassette G8(ABCG8).Results Compared with control group,obvious steatosis of liver tissue was observed,the serum levels of TC,TG and LDL-C were markedly increased(P<0.01),and the expressions of hepatic HMGCR,ABCG5 and ABCG8 were increased in the model group.Compared with the model group,hepatic steatosis was significantly reduced,the serum levels of TC,TG and LDL-C were markedly decreased(P<0.05)in the Shuangyu Tiaozhi Decoction group.The levels of mRNA and protein of HMGCR in the Shuangyu Tiaozhi Decoction group were markedly decreased(P<0.01)while the mRNA of ABCG5 and the mRNA and protein of ABCG5 were increased(P<0.01).Foremore,the effect of Shuangyu Tiaozhi Decoction by gavage for 8 weeks was more significant than gavage for 4 weeks.Conclusion Shuangyu Tiaozhi Decoction can reduce liver steatosis and lower blood lipids in hepercholesterolemic rats.The molecular mechanism may be related to down-regulation of the expression of HMGCR and up-regulation of expressions of ABCG5 and ABCG8 simultaneously.