HIF-1α、NF-κB在大鼠不同程度非酒精性脂肪肝中的表达

Expression of HIF-1α and NF-κB in non-alcoholic fat liver disease in rats

目的:探讨缺氧诱导因子1α(hypoxia-inducible factor 1α,HIF-1α)、核因子-κB(nuclear factor k a p p a B,N F-κB)在非酒精性脂肪肝炎(n o nalcoholic fat liver diseases,NAFLD)进展中的作用及其机制.方法:选50只♂SD大鼠随机分为正常组、模型组(高脂饮食4、8、12及16 wk组),每组10只.通过高脂饲料建立大鼠脂肪肝模型,取外周血及肝脏组织,进行血脂、肝功能、空腹血糖及病理组织学检查.Real-time-PCR法检测肝组织中HIF-1α、NF-κB的m RNA水平,多组计量资料比较采用成组设计的方差分析、Kruskal-Wallis H检验,两两比较采用LSD法,P<0.05为差异有统计学意义.结果:在高脂饮食第12周、16周,模型组的丙氨酸氨基转移酶(alanine amiotransferase,ALT)、三酰甘油(triglyceride,TG)和胆固醇(c h o l e s t e r o l,C H O L)水平与正常组相比均显著升高(P<0.05),而高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)的表达则显著下降(P<0.05).HIF-1α和NF-κB表达随着高脂饮食时间的延长,表达逐渐升高(P<0.05),与脂肪肝的严重程度呈正比,且HIF-1α的表达与NF-κB具有相关性(r=0.67,P<0.05).结论:HIF-1α/NF-κB信号在大鼠NAFLD的进展中起着一定的促进作用.

AIM： To investigate the role of hypoxia-inducible factor -1α （HIF-1α） and nuclear transcription factor κB （NF-κB） in the development of non-alcoholic fat liver disease （NAFLD） using a rat model. METHODS： Fifty SD rats were randomly divided into five groups （a normal group, a 4 wk model group, an 8 wk group, a 12 wk and a 16 wk group）. NAFLD was induced in rats by administration of a high fat diet. Serum biochemical parameters were tested, and fiver histological changes were observed. HIF-1α and NF-κB mRNA expression was detected by real-time PCR. RESULTS： Compared with the normal group, significant elevations of serum alanine amiotransferase （ALT）, triglyceride （TG）, and cholesterol （CHOL） and reduction of high-density lipoprotein cholesterol （HDL-C） were observed in rats given a high fat diet for 12 wk or 16 wk （P 〈 0.05）. In the model groups, liver steatosis, inflammation grade and degree of fibrosis were significantly aggravated. HIF-1α and NF- κB expression increased gradually with the severity of NAFLD （P 〈 0.05）. CONCLUSION： HIF-1α/NF-κB signaling may be related to the development of NAFLD.