摘要
目的观察二甲双胍对非酒精性脂肪性肝炎大鼠肝脏Resistin、NF-κB、TNF-α表达的影响,探讨二甲双胍防治NASH的作用机制。方法随机将24只大鼠分为正常组、NASH组和二甲双胍组,每组8只,以高脂饮食12周建立大鼠NASH模型,同时每天以60mg/(kg·d)的二甲双胍混悬液灌胃干预12周;观察大鼠体重及肝指数变化,油红O和HE染色观察肝脏组织病理学改变;Real time-PCR法检测肝组织Resistin、NF-κB、TNF-α等基因mRNA的表达,ELIAS法检测血清Resistin、TNF-α水平,免疫组化观察肝组织NF-κB核表达定位。结果 NASH组大鼠体重和肝指数较正常组明显增加(P<0.01),二甲双胍组大鼠体重和肝指数较NASH组显著降低(P<0.01);NASH组大鼠肝组织大量脂质沉积,明显肝细胞气球样变和小叶内炎症坏死灶等病理表现,二甲双胍组大鼠肝组织脂质沉积和炎症程度则有明显减轻;NASH组大鼠肝组织Resistin、NF-κB、TNF-α等基因mRNA表达较正常组显著增强(P<0.01),同时肝组织出现大量NF-κB p65蛋白阳性的核表达,血清Resistin、TNF-α水平也较正常组明显增高(P<0.01),应用二甲双胍干预后,大鼠肝组织Resistin、NF-κB、TNF-α等基因mRNA表达较NASH组显著减少(P<0.05),血清Resistin、TNF-α水平较NASH组明显降低,肝组织NF-κB p65蛋白阳性的核表达也明显的减少。结论二甲双胍能一定程度抑制高脂诱导的NASH大鼠抵抗素及相关炎性因子的表达,从而减轻NASH大鼠肝组织脂肪变程度和炎症损伤,防治NASH的进一步发展。
Objective To observe the effect of metforminon Resistin, NF - κB,TNF - α expression in the rats with non - alcoholic steatohepatitis（NASH） induced by fat- rich diet ;to explore the possible mechanism of Metformin in preventing and treating NASH. Methods Totally 24 male rats were randomly divided into the normal group （8 rats）, NASH group （g rats） andMetformin group （8 rats）. With high fat diet for 12 weeks to establish a rat model of NASH, at the time of model - making, the rats in the Metformin group were fed with Metformin liquid extract by daily gavage at the dosage of 60mg/ （ kg · d）. To observe the change of body weight and hepatic index in rats,the liver pathological change was evaluated under light microscope after HE staining and Oil red O. LiverResistin, NF - κB, TNF - ct gene mRNA expression was detected with Real - time - PCR, serum Resistin, TNF - α levels were detected with ELISA,liver tissue NF -κB nuclear expression was expressed by immunohistochemical staining. Results Body weight and liver index of rats in the NASH group was significantly higher than that in the normal group（ P 〈 0.01 ） , body weight and liver index of metformin group rats were significantly lower than those of NASH group （P 〈 0.01 ）. There were a lot of lipid deposition in liver tissue of rats in the NASH group, and obvious ballooning degeneration of liver cells and small lobe not leaf necrosis and inflammatory pathology in Metformin group. Rats liv- er lipid deposition and inflammation were significantly reduced. Resistin, NF - κB,TNF -α gene mRNA expression in NASH rats of Liver tissue was higher than that in control group （P 〈 0.01 ）. At the same time, the emergence of liver tissue have large number of nuclearex- pression of NF - κB p65 protein positive. Serum Resistin, TNF -α levels was significantly higher than that in the normal group （P 〈 0.01 ）. When metformin intervention, the expression of Resistin, NF - κB,TNF - αgene mRNA in the liver tissue of rats was less than that in NASH group（P 〈 0.05）. Serum Resistin, TNF - αlevels were significantly lower than those in NASH group, nuclear expression of NF - κB p65 protein positive in liver tissue was significantly reduced. Conclusion Metformin can to some extent restrain the expression ofNASH in rat resistin and inflammatory factors induced by high lipid diet,which can reduce the rats with non - alcoholicsteatohepatitis （NASH） of hepatic steatosis and inflammatory injury, and further development of prevention and control of NASH.
出处
《医学研究杂志》
2015年第11期64-67,70,共5页
Journal of Medical Research
基金
浙江省自然科学基金资助项目(Y2100170)
