木瓜对小鼠非酒精性脂肪肝形成的预防作用

Preventive Effect of Chaenomeles Fruits on Non-alcoholic Steatohepatitis in Mice

目的:复制小鼠非酒精性脂肪肝动物模型,观察木瓜对此模型的影响。方法:高脂饮食同时皮下注射小剂量四氯化碳复制小鼠非酒精性脂肪肝模型,在高脂饮食中添加木瓜对其进行干预,与正常饮食组对照。喂养5周后检测血清肝脏酶学(ALT、AST)、血脂(TG、CHO)水平;肝组织切片染色,显微镜观察肝组织病理变化;提取肝脏总RNA检测TLR-2、TLR-4、IL-1β、TGF-β、PD-L1等基因的表达情况,并进行统计学分析。结果:与正常组相比,模型组血清的肝功能和脂质水平上升,肝细胞形态明显改变,肝索消失或不清晰,相应基因表达水平上调;与模型组相比,木瓜干预组血清肝功能指标和脂质水平均显著下降,肝细胞气球样变较少,无明显肝细胞坏死,肝索存在,肝组织TLR和炎性因子表达水平明显下调。结论:木瓜对高脂饮食诱导的小鼠非酒精性脂肪肝有一定预防效果,该效应的发挥可能是通过调节TLR受体及死亡配受体表达,炎性因子的分泌而实现的。

Objective： To investigate the preventive effect of Chaenomeles fruits on non-alcoholic steatohepatitis（NASH） in mice.Methods： NASH model was established by high fat diet feeding combined with hypodermic injection at low dose of CCl4.NASH model group fed high fat diet containing Chaenomeles fruits for 5 consecutive weeks was served as Chaenomeles fruits-intervened group,while the mice in control group were fed normal diet.At the end of experiments,all the mice were sacrificed to analyze ALT,AST,TG and CHO levels in serum.Pathological changes of hepatic tissues were observed under microscope and mRNA expression of genes such as TGF-β,PD-L1,TLR-2,TLR-4 and IL-1β in hepatic tissues was detected by the real time RT-PCR technique.Results： Compared to normal mice,ALT,TG and CHO levels in serum exhibited an obvious increase in NASH mice and a significant reduction in Chaenomeles fruits-intervened NASH mice（P〈0.05）.Hepatocyte swelling,as well as neutrophilic infiltration and hepatocyte ballooning exhibited a decrease in Chaenomeles fruits-intervened NASH mice.Meanwhile,a significant decrease in hepatic TLR-2,TLR-4,IL-1 β,TGF-β and PD-L1 were also observed in Chaenomeles fruits-intervened NASH mice.Conclusion： Chaenomeles fruits have a significant preventive effect on non-alcoholic steatohepatitis in mice,which is achieved by regulating TLR and death receptor expression and the secretion of inflammatory cytokines.