塞来昔布对2型糖尿病大鼠非酒精性脂肪性肝炎肝组织过氧化物酶体增殖物激活受体Y／核因子-KB表达的影响  

Effects of celecoxib on expression of PPART and NF-kB in type 2 diabetes rats with non-alcoholic steatohepatitis

作　　者：田丰[1] 张亚杰[1] 汪颖厚[2] 

机构地区：[1]中国医科大学附属盛京医院消化内科,沈阳100004 [2]中国人民解放军第202医院普通外科

出　　处：《中华肝脏病杂志》2016年第8期590-595,共6页Chinese Journal of Hepatology

基　　金：辽宁省科学技术计划项目（2010225034）

摘　　要：目的探讨塞来昔布对2型糖尿病大鼠非酒精性脂肪性肝炎的保护作用及其对过氧化物酶体增殖物激活受体（PPAR）v／核因子（NF）-KB表达的影响。方法雄性SD大鼠36只，随机等分为对照组、模型组、模型＋celecoxib组，共3组。造模成功后取血清及肝脏组织。检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平；HE及油红O染色观察肝脏病理改变；免疫组织化学、Westernb10t检测肝脏PPARY、NF—KBp65、COX-2蛋白的表达。计量资料两两比较采用f检验。结果模型组ALT、AST水平分别为（301．8±5．40）U／L和（345．4±9．63）U／L，高于对照组的分别为（33．00±4．06）U／L和（76．6±7．64）U／L和模型＋celecoxib组的分别为（88．80±13．07）U／L和（99．8±20．51）U／L。HE及油红O染色结果显示肝细胞脂肪变性及肝组织炎症。免疫组织化学结果显示模型组的NF—KBN5和COX-2积分吸光度分别为4．04E5±2．42FA和6．62E5±2．64E4，高于对照组（分别为4．23E4±6．82E3和4．82E4±3．71E3），t值分别为48．86，72．93，尸值均〈0．01；同时又高于模型＋celecoxib组（分别为2．74E5±4．38E4和2．31E5±2．09E4），t值分别为9．02，40．51，P值均〈0．01。模型组PPARg积分吸光度值（4．50E4±2．38E3）和对照组（4．26E4±5．09E3）相比差异无统计学意义，但模型＋celecoxib组PPARY积分吸光度值（3．22E5±1．54E4）较模型组升高，f值为61．82，JD〈0．01。Westernblot结果显示模型组NF—KBp65、COX-2蛋白相对表达量（分别为4．93±0．76和3．04±0．23）高于对照组（分别为1．00±0．13和1．00±0．15），t值分别为11．44，16．64，P值均〈0．01；同时又高于模型＋celecoxib组（分别为2．44＋-0．32和1．26±0．11），t值分别为6．80，15．81，P值均〈0．01。以对照组（1．00±0．15）为参照，模型＋celecoxib组PPARY蛋白相对表达量�Objective To investigate the protective effect of celecoxib against non- alcoholicsteatohepatitis and its impact on the expression of peroxisome proliferator-activated receptor gamma （PPART）/NF-kB in type 2 diabetes rats. Methods Thirty-six male Sprague-Dawley rats were randomly and equally divided into three groups： control group, model group, and model＋celecoxib group. After the model was successfully established, all rats were sacrificed to isolate serum and liver tissues. Serum levels of alanine transaminase （ALT） and aspartate aminotransferase （AST） were measured, liver pathological changes were analyzed by HE and oil red O staining, and the protein expression of hepatic PPARy, NF-v,.B p65, and COX- 2 was determined by immunohistochemistry and Westem blot. Results were statistically analyzed by t-test. Results The levels of ALT and AST in the model group （301.8±5.40 and 345.4±9.63 U/L） were significantly higher than those in the control group （33±4.06 and 76.6±7.64 U/L） and those in the model＋celecoxib group （88.8±13.07 and 99.8±20.51 U/L）. HE and oil red O staining demonstrated hepatic steatosis and inflammation in liver tissues. Immunohistochemical results showed that the integral optical densities （IODs） of NF-kB p65 and COX-2 in the model group （4.04E5±2.42E4 and 6.62E5±2.64E4） were significantly higher than those in the control group （4.23E4±6.82E3 and 4.82E4±3.71E3） （t = 48.86 and 72.93, bothP 〈 0.01） and those in the model＋celecoxib group （2.74E5±4.38E4 and 2.31E5±2.09E4） （t = 9.02 and 40.51, both P 〈 0.01）. There was no significant difference in the IOD of PPARy between the model group （4.50E4±2.38E3） and the control group （4.26E4±5.09E3）. However, the IOD of PPAR-/in the model＋celecoxib group （3.22E5±1.54E4） was significantly higher than that in the model group （t = 61.82, P 〈 0.01）. Western blot analysis showed that the relative protein levels of hepatic NF-v,B p65 and COX-2 in the model group （4.93~0.7

关 键 词：过氧化物酶体增殖物激活受体 NF-KB 塞来昔布 

分 类 号：R587.1[医药卫生—内分泌]