烟酸对非酒精性脂肪性肝病大鼠模型脂质代谢的影响

Effects of niacin on lipid metabolism in rat model of non-alcoholic fatty liver disease

目的研究烟酸对非酒精性脂肪性肝病(NAFLD)大鼠模型脂质代谢的影响。方法 40只SD大鼠随机分成对照组、模型组、干预1组(0.5%烟酸)、干预2组(1%烟酸),采用高脂饮食饲养大鼠8周诱导NAFLD模型,采用试剂盒对各组大鼠血清ALT、AST,血清及肝脏组织中总胆固醇(TC)、甘油三酯(TG)、游离脂肪酸(FFA)、肝组织脂质过氧化产物(MDA)进行测定,显微镜下观察肝组织病理学形态改变。各组间比较使用单因素方差分析,方差齐时用LSD-t检验进行两两比较,方差不齐时用Tamhane'T2检验。结果各干预组与模型组相比,血清ALT、AST、TC、TG、FFA显著降低,差异均有统计学意义(P值均<0.05);干预2组与模型组相比,肝组织TG、TC、FFA、MDA含量差异均有统计学意义(P值均<0.05);干预1组与模型组比较,PPARαmRNA表达显著增加,差异有统计学意义(P=0.026),DGAT2 mRNA、SREBP1c mRNA表达显著降低,差异有统计意义(P值分别为0.019、0.008),干预2组与干预1组比较,DGAT2 mRNA、SREBP1c mRNA表达降低,差异有统计学意义(P值均<0.05)。与模型组相比,干预组肝细胞脂肪变性程度缓解,中央区炎症细胞浸润程度减轻。结论烟酸调节非酒精性脂肪肝病动物模型的脂肪代谢,减轻脂质氧化应激反应,通过调节PPARα、DGAT2、SREBP1c mRNA的表达,明显改善肝细胞脂肪变性及纤维化,从而对NAFLD有保护作用。

Objective To investigate the effects of niacin on the lipid metabolism in rat model of non - alcoholic fatty liver disease （NAFLD）. Methods Forty Spragne -Dawley rats were randomly divided into control group, model group, intervention group 1 （0.5% niacin） , and intervention group 2 （ 1% niacin）. Rats were fed with high - fat diet for 8 weeks to induce an NAFLD model. The serum lev- els of alanine aminotransferase （ALT） and aspartate aminotransferase, levels of total cholesterol （TC）, triglyceride, and free fatty acid in serum and liver tissue, and level of malondialdehyde （MDA） in liver tissue were measured using assay kits. The morphological and his- topathological changes in the liver were observed under a microscope. Comparison of data between groups was made by univariate analysis of variance using SPSS software; moreover, least significant difference test （equal variance assumed） and Tamhane＇s T2 test （equal variance not assumed） were used for pairwise comparison. Results Compared with the model group, every intervention group had significantly lower levels of ALT, TC, AST, TG, and FFA （ all P 〈 0.05 ） in serum and level of MDA in liver tissue （ P 〈 0. 05 ）, and had significantly in- creased expression of PPARot mRNA （ P 〈 0.05 ） , DGAT2 mRNA （ P 〈 0.05 ） , and SREBP1 c mRNA （ P 〈 0.05 ）. Intervention group 2 had significantly reduced expression of DGAT2 mRNA and SREBP1 c mRNA compared with intervention group 1 （ P 〈 0.05 ）. Compared with the model group, the intervention groups had relieved fatty degeneration of hepatocytes and alleviated inflammatory cell infiltration in the centrilobular portion of the liver. Conclusion Niacin regulates lipid metabolism in NAFLD animal models, reduces lipid oxidative stress, and significantly reduces liver steatosis and fibrosis by regulating the expression of PPARα mRNA, DGAT2 mRNA, and SREBP1c mRNA, so as to realize the protective effect against NAFLD.