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  

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

作　　者：程楠[1] 池信锦[1] 李玺[2] 葛缅[1] 高婉菱[1] 黑子清[1] 

机构地区：[1]中山大学附属第三医院麻醉科,广东广州510630 [2]中山大学附属第三医院甲乳外科,广东广州510630

出　　处：《中国病理生理杂志》2015年第9期1637-1641,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81471892);广东省自然科学基金资助项目(No.2014A030313199);广东省科技计划(No.2013B021800181);中山大学青年教师培育项目(No.14ykpy24)

摘　　要：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(P<0.05)。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。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 ortho-topic 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 tis-sue sections were stained to visualize the damage .The expression of PPARγand 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-αand 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 signifi-cantly higher , and the serum concentrations of DAO and FABP 2 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 PPARγexpression was obviously up-regulated in the intestinal tissues, the nuclear translocation of NF-κB was reduced and the concentrations of IL-6 and TNF-αwere decreased .CONCLUSION： During perioperative period of OALT in rats , the inflammatory responses are obvious .Furthermore, obvious intestinal injury oc-curs .PPARγagonist rosiglitazone obviously up-regulates PPARγexpression and inhibits the inflammation in the intestines , thus protecting against intestinal injury in rats undergoing OALT .

关 键 词：过氧化物酶体增殖物激活受体Γ 自体原位肝移植 肠损伤 罗格列酮 炎症反应 

分 类 号：R363[医药卫生—病理学]