慈菇消脂丸对NF-κB介导的非酒精性脂肪肝病大鼠肝细胞凋亡的干预作用

来源 :北京中医药大学学报 | 被引量 : 0次 | 上传用户:wangxiao8910
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目的通过观察慈菇消脂丸对高脂饮食诱导非酒精性脂肪肝病(NAFLD)大鼠肝细胞凋亡相关调控基因核转录因子κB(NF-κB)、B细胞淋巴瘤-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)表达的影响,探讨解毒化痰法治疗NAFLD的作用机制。方法 60只SPF级健康雄性Wistar大鼠,随机分为6组:正常对照组,模型组,慈菇消脂丸高、中、低剂量组,盐酸吡格列酮组,每组10只。采用高脂饮食喂饲大鼠建立NAFLD模型后,连续药物治疗6周。给药结束后,处死全部动物,取肝脏和血清。全自动生化分析仪检测各组大鼠肝功、血脂;HE染色观察肝脏的组织形态学特点;透射电子显微镜观察肝细胞的超微结构;Western Blot技术检测肝组织NF-κB、Bcl-2、Bax的表达。结果与正常组比较,模型组大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(TG)、胆固醇(TC)、低密度脂蛋白(LDL-C)水平升高(P<0.01);肝组织呈中重度脂肪变性并同时伴有肝细胞凋亡;肝组织中NF-κB、Bax蛋白表达增强(P<0.01),Bcl-2蛋白表达减低(P<0.01),Bcl-2/Bax比值降低(P<0.01)。与模型组比较,慈菇消脂丸各剂量组大鼠血清ALT、AST、TG、TC水平降低(P<0.01);肝组织NF-κB、Bax蛋白表达减低(P<0.01),Bcl-2蛋白和Bcl-2/Bax比值升高(P<0.05)。与盐酸吡格列酮组比较,慈菇消脂丸高剂量下调NF-κB蛋白、上调Bcl-2蛋白表达的作用更显著(P<0.01)。结论慈菇消脂丸能够明显改善NAFLD大鼠肝功及血脂;上调Bcl-2蛋白表达,降低NF-κB、Bax蛋白表达,使Bcl-2/Bax比值升高,从而抑制肝细胞凋亡,起到防治NAFLD的作用。 Objective To observe the effect of Zijie Xiao Zhi Wan on the expression of nuclear factor-κB (NF-κB), B-cell lymphoma-2 (Bcl-2) gene in hepatocellular apoptosis induced by high fat diet in rats with non-alcoholic fatty liver disease (NAFLD) 2), Bcl-2-related protein B (Bax) expression, explore the mechanism of detoxification phlegm treatment of NAFLD. Methods Sixty SPF healthy male Wistar rats were randomly divided into 6 groups: normal control group, model group, Zijin Xiaozhi Wan high, medium and low dose group, pioglitazone hydrochloride group, 10 rats in each group. The rats were fed with a high-fat diet to establish a model of NAFLD, continuous drug treatment for 6 weeks. After the administration, all animals were sacrificed and the liver and serum were taken. The hepatic function and blood lipids were detected by automatic biochemical analyzer. The histopathological features of liver were observed by HE staining. The ultrastructure of hepatocytes was observed by transmission electron microscopy. The expressions of NF-κB, Bcl-2, Bax expression. Results Compared with the normal group, the levels of serum ALT, AST, TG, TC and LDL-C in the model group increased (P <0.01). Hepatic tissues were moderately and severely steatosis accompanied with hepatocellular apoptosis. The expression of NF-κB and Bax in hepatic tissue was increased (P <0.01), the expression of Bcl-2 protein was decreased -2 / Bax ratio decreased (P <0.01). Compared with the model group, the serum ALT, AST, TG and TC levels in the ZJD group were significantly decreased (P <0.01), the expressions of NF-κB and Bax in the liver tissue were decreased (P <0.01) The protein and Bcl-2 / Bax ratio increased (P <0.05). Compared with pioglitazone hydrochloride group, Sagitailiaoyan pill could significantly up-regulate the expression of Bcl-2 protein (P <0.01) by down-regulating NF-κB protein. Conclusion Sagitailiaoshi Pill can significantly improve the liver function and blood lipids in NAFLD rats; upregulate the expression of Bcl-2, decrease the expression of NF-κB and Bax, increase the ratio of Bcl-2 / Bax, Play a role in the prevention and treatment of NAFLD.
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