降脂益肝冲剂对NAFLD大鼠肝脏ChREBP mRNA表达的影响

Effect of Jiangzhi Yigan Chongji on ChREBP mRNA in the liver of rats with non-alcoholic fatty liver disease

目的观察降脂益肝冲剂对非酒精性脂肪性肝病(NAFLD)大鼠肝脏糖类应答原件结合蛋白(ChREBP)mRNA表达的影响。方法24只雄性Wistar大鼠随机分为3组:正常组普通饲料喂养,模型组和治疗组高脂饮食喂养。治疗组在高脂饮食8周后给予降脂益肝冲剂,同时模型组和正常组给予等量的生活饮用水灌胃,12周末处死各组大鼠。观察动物一般情况,肝组织脂肪变性及炎症活动程度,测定血清TNF-α、ALT、AST,空腹血糖(FBG)、空腹胰岛素(FINS),并计算胰岛素敏感指数(ISI);RT-PCR法检测肝组织ChREBP mRNA相对含量。结果在正常组肝脏组织探测到ChREBP mRNA的表达较低(0.61±0.05),模型组其表达量显著升高(0.87±0.07,P<0.01),与模型组相比治疗组则显著下降(0.75±0.04,P<0.01)。在模型组中,ChREBP mRNA相对表达量与血清TNF-α、ALT、AST水平、肝脏炎症活动度计分呈显著正相关(r=0.845,0.818,0.789,0.711,P<0.01或P<0.05),与ISI呈负相关(r=-0.820,P<0.05)。治疗组上述各项指标均得到显著改善。结论ChREBP与反映肝脏炎症程度及肝功能的指标密切相关,可能在NAFLD的发病中起重要作用,降脂益肝冲剂对NAFLD有一定的治疗作用。

Objective To explore the role of carbohydrate response element binding protein（ChREBP） in the pathogenesis of non-alcoholic fatty liver disease （NAFLD）. Methods Twenty-four male Wistar rats were randomized into three groups （ eight rats in each group） ：normal group,model group and treated group. The rats were given Jiangzhi Yigan Chongji（ 1 ml/100 g,0.8 g/ml,twice a day） by intragastric administration after high fat diet for 8 weeks in treated group, while in normal group and model group were given drinking water by the same means,respectively. After 12 weeks, they were killed. ChREBP mRNA in liver of rats with NAFLD induced by high-fat diet was detected with RT-PCR. Levels of alanine aminotransferase（ALT） and aspirate aminotransferase（AST） were detected by an automatic biochemistry analyzer, fasting blood glucose （FBG）was detected by glucose oxidase method, and tumor necrosis factor α （TNF-α） and fasting insulin（FINS） in serum were detected by radioimmunoassay. Degrees of fatty degeneration were observed. Results The level of ChREBP mRNA in liver tissues in model group was higher than that in normal group（0.87 ± 0.07 vs 0.61 ± 0.05, P 〈 0.01 ）, and also higher than in treated group （0.75 ± 0.04, P 〈 0.01 ）. Expression of ChREBP mRNA was positively correlated with TNF-α, ALT and AST, and the degree of fatty degeneration （ r = 0. 845,0. 818,0. 789 and 0. 711, P 〈 0.01 or P 〈 0. 05 ） in model group, but negatively correlated with ISI （ r = - 0. 820, P 〈 0.05 ）. The above indices were improved in treated group. Conclusion ChREBP may play an important role in the damage of NAFLD. Jiangzhi Yigan Chongji has a therapeutic effect on NAFLD.