摘要
目的研究大鼠非酒精性脂肪性肝炎(NASH)肝纤维化形成过程中肝组织核因子过氧化物酶体增殖物活化受体γ(PPARγ)的表达变化及意义。方法建立脂肪性肝纤维化大鼠模型,HE和Massson染色观察肝组织病理学变化,RT-PCR和免疫组织化学检测核转录因子PPARγ以及反映肝星状细胞(HSC)活化的特异性标记α-平滑肌肌动蛋白(α-SMA)的mRNA和蛋白表达变化。结果①模型组大鼠8w肝脏病理学呈现单纯性脂肪肝,12-16w呈现脂肪性肝炎,24w呈现脂肪性肝纤维化的病理学变化特点。②RT-PCR显示模型组PPARγ mRNA于高脂喂养8w即明显上调为0.84±0.07,对照组为0.54±0.12,P<0.05.12w达高峰为1.16±0.14,16w脂肪性肝炎明显时表达开始下调为0.73±0.05,24w下调更为明显为0.34±0.15,与对照组比较,差异均有统计学意义(P<0.05);而α-SMA mRNA于高脂喂养12w开始增高,24w达高峰,与对照组比较,差异均有统计学意义(P<0.01)。③免疫组织化学显示模型组PPARγ主要在脂肪变性的肝细胞核表达增高,在肝纤维化形成部位其阳性染色明显减少,而α-SMA阳性细胞主要在纤维间隔、汇管区等纤维形成区域表达增多。结论单纯性脂肪肝时,PPARγ的高表达可能是机体的一种适应性反应,随着高脂诱导的肝损伤程度的加重,PPARγ的表达逐渐降低与肝星状细胞的激活密切相关,从而促进脂肪性肝纤维化的发生、发展。
Objective To study the expression and significance of PPARγ in the development of nonalcoholic fatty liver fibrosis. Methods To establish a rat fatty liver fibrosis model by a high fat feeding,Hepatic expressions of PPARγ and α-SMA were observed by RT-PCR and immunohistochemistry.We also investigated the pathologic features and the degreed of liver fibrosis. Results （1）In the model group, liver pathology showed simple fatty liver （8 weeks） - steatohepatitis （12-16 weeks） - Fatty Liver fibrosis （24 weeks） of the characteristics of pathological changes. （2）RT-PCR showed that the expression of PPARγ mRNA were significance increased in the high fat diet for 8 weeks, Compared with the control group significantly （0.84±0.07 vs. 0.54 ± 0.12, P〈0.05）, peaked in 12^th weeks （1.16± 0.14, P〈0.01）,then decreased gradually at 16th week （0.73±0.05）, 24 weeks decline obviously （0.34±0.15）;and α-SMA mRNA increased at the 12^th week （0.46±0.19 vs 0.30±0.07, P 〈 0.05）, peaked in 24th week （1.08±0.19）; （3）Immunohistochemistry showed that in the model group PPARγ mainly in the fatty degeneration of the liver ceils increased expression, Liver fibrosis in positive staining were significantly reduced, and α-SMA-positive cells in the main fiber partitions, Exchange Zone fiber formation of regional expression increased. Conclusions Simple fatty liver, high- PPARγ expression of the body is an adaptive response, With the high fat-induced hepatic injury aggravated , the decreased gradually expression of PPARγ is closely related to the activation of hepatic stellate cells, thereby promoting the development of fatty liver fibrosis
出处
《药品评价》
CAS
2007年第4期298-302,共5页
Drug Evaluation
