甘氨酸对NASH大鼠肝组织环氧合酶-2表达的影响

Effect of glycine on cyclooxygenase-2 expression in the livers of rats with non-alcohol steatohepatitis

目的探讨环氧合酶-2在非酒精性脂肪性肝炎发病机制中的作用以及甘氨酸对其表达的影响。方法选择雄性Wistar大鼠54只,随机分为对照组、高脂饮食组和甘氨酸干预组,比较实验第8、12和16周末动物血浆ALT和内毒素水平及肝组织COX-2的表达情况。结果在实验第12周和16周末,脂肪肝组动物血浆ALT较对照组明显增高(P<0.05),各期脂肪肝组和甘氨酸组动物腹主动脉血内毒素水平与对照组比较均无差异,而门静脉血内毒素水平明显上升,腹主动脉血与相对应的门静脉血内毒素比较有显著性差异(P<0.01);在第16周脂肪肝组和甘氨酸组COX-2表达呈阳性,甘氨酸处理组积分光密度值比脂肪肝组明显降低(P<0.05);在对照组、实验第8周和12周脂肪肝组肝内无COX-2mRNA表达,但在第16周脂肪肝组动物肝内COX-2的相对表达量为0.67±0.04,甘氨酸组为0.43±0.04,两者比较有显著性差异(P<0.05);血浆内毒素水平与COX-2表达呈正相关(r=0.58,P<0.01)。结论肠源性内毒素血症上调肝组织COX-2表达,后者在NASH发病机制中起着重要的作用,甘氨酸能降低内毒素水平,并使NASH大鼠肝内COX-2表达减少。

Objective To explore the pathogenesis of cyclooxygenase-2 （Cox-2） expression in the livers of rats with non-alcohol steatohepatitis and the effect of glyeine on COX-2 expression. Methods Fifty-four male Wistar rats were divided randomly into control group,model group and glycine treatment group. The levels of endotoxin in the portal vein and abdominal aorta at 8,12 and 16 wk were detected,respectively. Hepatic expressions of COX-2 were detected by RT-PCR and immunohistochemistry. Results The endotoxin level in the portal vein of the fatty liver groups dramatically increased compared with that of the control group at 8,12 and 16wk,and the level of endotoxin was significantly different between abdominal aorta and portal vein in the same groups. Upregulation of COX-2 in the livers of fatty liver rats was obvious at 16 wk. Conclusion The intestinal endotoxemia-induced upregulation of COX-2 plays a primary role in the pathogenesis of non-alcohol steatohepatitis and glycine can decrease the level of endotoxin.