摘要
目的观察大鼠非酒精性脂肪性肝炎(NASH)伴肝纤维化模型形成过程中,肝脏内毒素受体表达的动态变化,以探讨NASH的发病机制。方法 45只雄性SD大鼠以高脂饮食喂养,分批于实验 8,12、16、24周处死。免疫组织化学法观察CD14表达,逆转录聚合酶链反应(RT-PCR)法观察4型toll 样受体(TLR4)mRNA表达,RT-PCR法和酶联免疫吸附法分别测定肝脏和血清肿瘤坏死因子a(TNF a) 表达。同期正常饮食饲养大鼠作对照。结果实验8周大鼠单纯性脂肪肝阶段肝脏CD14和TLR4的表达就较正常对照上调(25．9±11．9对12．4+5．7、1．75±0．81对O．98±0．33,P<0．01和P<0．05),12周随着脂肪性肝炎的出现进行性增高(61．8±21．9和1．88±0．72,P值均<0．05),于16周达高峰(71．5±21．3 对5．64±0．87,P值均<0．01),24周略有回落(67．7±16．6和4．98±0．72,P值均<0.01)。肝脏和血清 TNF a表达也从8周开始上调,此后一直维持高水平表达。结论大鼠NASH形成过程中,肝脏内毒素受体CD14和TLR4表达逐渐上调。这可能是NASH大鼠内毒素肝损伤敏感性增强的原因之一,在NASH的发病中起了重要作用。
Objective The expression of hepatic lipopolysaccharide （LPS） receptors in a rat nonalcoholic steatohepatitis （NASH） model was studied in order to explore the pathogenesis of NASH. Methods Forty-five male SD rats were fed with a high fat diet. These rats were sacrificed after high fat feeding at 8, 12, 16, 24 weeks. Hepatic expressions of CD14 were observed by immunohistochemistry and expressions of TLR4 were detected by RT-PCR. Hepatic expressions and serum levels of TNFa were measured by RT-PCR and ELISA. Some rats fed with normal rat food served as controls. Results At the 8th week fatty livers appeared, and hepatic expressions of CD14 （25.9±11.9） and TLR4mRNA （1.75±0.81） were upregulated compared to those in the control group （25.9±11.9 vs 12.4±5.7, 1.75±0.81 vs 0.98±0.33, P 〈 0.01, t 〉 2.756 and P 〈 0.05, t 〉 2.045）. The hepatic expressions of the two kinds of receptors increased with the appearance of NASH at week 12 （61.8±21.9 and 1.88±0.72, P 〈 0.01, t 〉 2.756 and P 〈 0.05, t 〉 2.045）, They reached to their peaks at week 16 （71.5±21.3 and 5.64±0.87, both P 〈 0.01 and t 〉 2.756）, and decreased slightly at week 24 （67.7±16.6 and 4.98±0.72, both P 〈 0.01 and t 〉 2.756）. Hepatic expressions and serum levels of TNFa also increased starting at week 8, and remained at that high level from week 8 to week 24. Conclusion The hepatic expressions of CD14 and TLR4 were up-regulated gradually in the established rat NASH model, It may be one of the factors responsible for the increase of hepatic sensitivity to LPS injury of the NASH rats and may play an important role in the pathogenesis of NASH.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2006年第1期49-52,共4页
Chinese Journal of Hepatology
基金
上海市卫生局面上项目(034036)
关键词
脂肪肝
内毒素类
鼠科
Fatty liver
Endotoxins
Muridae
