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

胆管结扎（BDL）后24小时采集的血中血清15d-PJ2水平显著升高。这一结果表明15d-PGJ2的释放在BDL后的早期过程中上调，也提示BDL后pparty系统被激活，BDL后的肝损伤与炎症反应的激活和血管收缩物的产生上调密切相关。我们采用实时RT-PCR检测Sham、BDL和GW9662中炎症因子和血管收缩基因的基因表达，并检测IL-1β、IL-6、IL-12、IFNy和TNF-α作为代表性炎症因子的基因表达。检测ET-1和TXA2合成酶（TXS）作为代表性血管收缩因子的基因表达。BDL后，所有炎症细胞因子基因的表达均上调，这些变化在给药GW9662后进一步增强。与Sham组相比，BDL组血清ROS水平显著升高，GW9662治疗对ROS水平无影响。这些结果表明，pparty的激活通过减少炎症细胞因子和血管收缩剂的产生来保护肝脏免受肝损伤。pparty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.