PPARγ激动剂罗格列酮通过抑制炎症反应减轻肝移植大鼠围术期肠损伤

目的:观察过氧化物酶体增殖物激活受体γ(PPARγ)激动剂罗格列酮对自体原位肝移植大鼠围术期肠组织中PPARγ表达、NF-κB激活及肠损伤的影响。方法:SD大鼠40只,随机分为对照(control)组、假手术(sham)组、原位自体肝移植(OALT)组、罗格列酮(0.3 mg/kg,iv)预处理(ROS+OALT)组。建立自体原位肝移植模型,在肝脏再灌注后8 h时取肠组织,观察肠组织病理学变化,检测肠组织PPARγ蛋白表达、NF-κB核转运激活情况、肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)浓度以及血清二胺氧化酶(DAO)和脂肪酸结合蛋白2(FABP2)水平。结果:与sham组相比,OALT组大鼠肠黏膜存在明显的病理学损伤,肠黏膜病理Chiu’s评分明显增高,血清DAO和FABP2升高(P0.05)。罗格列酮预处理后,大鼠肠黏膜损伤减轻,肠黏膜病理Chiu’s评分降低,血清DAO和FABP2降低,肠组织PPARγ表达明显上调,NF-κB p65亚基核转位减少,肠组织IL-6和TNF-α浓度降低。结论:自体原位肝移植大鼠围术期炎症反应明显,存在明显的肠道损伤;PPARγ激动剂罗格列酮明显上调PPARγ表达,抑制肠道的炎症反应,减轻自体原位肝移植大鼠围术期的肠损伤。

Effect of peroxisome proliferator-activated receptor γ agonist rosiglitazone on intestinal injury in rats undergoing orthotopic autologous liver transplantation by inhibiting inflammatory response

AIM: To investigate the effect of rosiglitazone, a peroxisome proliferators-activated receptor γ(PPARγ) agonist, on the expression of PPARγ, the activation of NF-κB and intestine injury in the rats undergoing orthotopic autologous liver transplantation(OALT).METHODS: Sprague-Dawley male rats were randomly divided into 4 groups:control group, sham group, OALT group and rosiglitazone(0.3 mg/kg, iv) pretreatment(ROS+OALT) group. The OALT model was established, and the intestinal tissues were collected 8 h after the liver reperfusion. The intestinal tissue sections were stained to visualize the damage. The expression of PPARγ and NF-κB in the tissues, the concentrations of diamine oxidase(DAO) and fatty acid-binding protein 2(FABP2) in the serum and the concentration of TNF-α and IL-6 in the tissues were measured.RESULTS: Compared with sham group, the intestinal mucosa of the rats showed obvious pathological injury after liver reperfusion in OALT group and ROS group, the Chiu,s scores of intestinal mucosa was significantly higher, and the serum concentrations of DAO and FABP2 increased(P<0.05). After rosiglitazone pretreatment, the injury of intestinal mucosa of the rats was alleviated, the Chiu,s scores was lower and the serum concentrations of DAO and FABP2 decreased(P<0.05), the PPARγ expression was obviously up-regulated in the intestinal tissues, the nuclear translocation of NF-κB was reduced and the concentrations of IL-6 and TNF-α were decreased.CONCLUSION: During perioperative period of OALT in rats, the inflammatory responses are obvious. Furthermore, obvious intestinal injury occurs. PPARγ agonist rosiglitazone obviously up-regulates PPARγ expression and inhibits the inflammation in the intestines, thus protecting against intestinal injury in rats undergoing OALT.