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多烯磷脂酰胆碱干预对非酒精性脂肪性肝炎的影响及相关机制

The effect of polyene phosphatidyl choline intervention on nonalcoholic steatohepatitis and related mechanism.

作者信息

Cao Mingbo, Li Xiuling, Zhang Bingyong, Han Shuangyin, Yang Yuxiu, Zhou Bingxi, Zhang Yanri

机构信息

Department of Digestive Medicine, Henan Provincial People's HospitalZhengzhou 450003, China; Department of Digestive Medicine, Zhengzhou University People's HospitalZhengzhou 450003, China.

出版信息

Am J Transl Res. 2016 May 15;8(5):2325-30. eCollection 2016.

Abstract

Nonalcoholic steatohepatitis (NASH) has similar clinical pathological changes to alcoholic hepatitis. It shows increased incidence and young trend year by year. Polyene phosphatidyl choline (PPC) is widely used in clinic for liver disease treatment. The effect and mechanism of PPC on NASH have not been fully elucidated. Thirty healthy male Wistar rats were randomly equally divided into control, NASH group, and PPC group. NASH model was established by high fat diet. PPC was intraperitoneal injected to NASH rat from the second week at 80 mg/kg·d for three weeks. Body weight, liver weight index, ALT, AST, TG, and TC were tested. TNF-α and IL-1β levels were detected by ELISA. NF-κB mRNA and protein expression in liver tissue were determined by real time PCR and Western blot. SOD activity and ROS content were measured by colorimetry. NASH rat presented significantly elevated body weight and liver weight index, increased ROS content, declined SOD activity, enhanced liver function and inflammatory factors expression, and upregulated NF-κB mRNA and protein levels compared with control (P < 0.05). PPC intervention obviously reduced body weight and liver weight index, declined ROS content, amplified SOD activity, decreased liver function, weakened inflammatory factor TNF-α and IL-1β expression, and downregulated NF-κB mRNA and protein levels compared with NASH group (P < 0.05). PPC can play a treatment effect on NASH through regulating oxidative balance, inhibiting inflammatory factors and NF-κB signaling pathway.

摘要

非酒精性脂肪性肝炎(NASH)具有与酒精性肝炎相似的临床病理变化。其发病率逐年上升且呈年轻化趋势。多烯磷脂酰胆碱(PPC)在临床上广泛用于肝病治疗。PPC对NASH的作用及机制尚未完全阐明。将30只健康雄性Wistar大鼠随机等分为对照组、NASH组和PPC组。通过高脂饮食建立NASH模型。从第2周起对NASH大鼠腹腔注射PPC,剂量为80mg/kg·d,共3周。检测体重、肝脏重量指数、谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(TG)和总胆固醇(TC)。采用酶联免疫吸附测定法(ELISA)检测肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平。通过实时聚合酶链反应(real time PCR)和蛋白质免疫印迹法(Western blot)测定肝组织中核因子-κB(NF-κB)的信使核糖核酸(mRNA)和蛋白表达。采用比色法测定超氧化物歧化酶(SOD)活性和活性氧(ROS)含量。与对照组相比,NASH大鼠体重和肝脏重量指数显著升高,ROS含量增加,SOD活性下降,肝功能及炎症因子表达增强,NF-κB mRNA和蛋白水平上调(P<0.05)。与NASH组相比,PPC干预明显降低了体重和肝脏重量指数,降低了ROS含量,增强了SOD活性,降低了肝功能,减弱了炎症因子TNF-α和IL-1β的表达,下调了NF-κB mRNA和蛋白水平(P<0.05)。PPC可通过调节氧化平衡、抑制炎症因子及NF-κB信号通路对NASH发挥治疗作用。

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