The role of PPARy in bile duct ligation-induced hepatic injury in rats

在胆管结扎（BDL）后24小时收集的血液中，血清15 d-PJ 2水平显著升高。结果提示，BDL后早期15 d-PGJ_2释放增加，提示BDL后PPARy系统被激活，BDL后肝损伤与炎症反应的激活和血管收缩物质的产生增加密切相关。我们使用实时RT-PCR检测了Sham、BDL和GW 9662中炎性细胞因子以及血管收缩基因的基因表达。IL-1β、IL-6、IL-12、IFN γ和TNF-α的基因表达被测量为代表性炎性细胞因子。检测ET-1和TXA 2合酶（TXS）的基因表达，作为代表性的血管收缩剂。所有炎性细胞因子基因的表达在BDL后上调。这些变化通过施用GW 9662进一步增强。BDL组血清ROS水平显著高于Sham组，GW 9662处理对血清ROS水平无影响，提示PPARy的激活可能通过减少炎症因子和血管收缩剂的产生而保护肝脏免受肝损伤。PPARy激活可能是BDL大鼠肝损伤的有效治疗选择。

Serum 15d-PJ2 levels were significantly increased in the blood collected 24h after bile duct ligation(BDL). This result indicated that the release of 15d-PGJ2 was upregulated during the early time course after BDL The result also suggested that PPARy system is activated after BDLThe liver injury after BDL is closely related to the activation of inflammatory response and upregulated production of vasoconstrictors. We examined the gene expression of inflammatory cytokines as well as vasoconstrictor genes in Sham, BDL and GW9662 using real-time RT-PCR The gene expression of IL-1β, IL-6, IL-12, IFNy, and TNF-α were measured as representative inflammatory cytokines. The gene expression of ET-1 and TXA2 synthase(TXS) were examined as representative vasoconstrictors. The expression of all inflammatory cytokine genes were upregulated after BDL These changes were further enhanced by an administration of GW9662. The levels of serum ROS in BDL group was significantly higher as compared to those in Sham group, either the treatment with GW9662 did not affect the levels of ROS.These results indicated that the activation of PPARy protects the liver against hepatic injury through the attenuated production of inflammatory cytokines and vasoconstrictors. PPARy activation might be a potent therapeutic option for hepatic injury in BDL rats.