塞来昔布对2型糖尿病大鼠非酒精性脂肪肝病相关的胰岛素抵抗的影响  

Effect of Celecoxib on the Insulin Resistance of Non-alcoholic Fatty Liver Disease in Type 2 Diabetes Mellitus Rats

作　　者：张亚杰[1] 靳爽[1] 姜宁[1] 田丰[1] 

机构地区：[1]中国医科大学附属盛京医院第一消化内科,沈阳110004

出　　处：《中国医科大学学报》2016年第1期39-44,共6页Journal of China Medical University

基　　金：辽宁省科学技术计划项目(2010225034)

摘　　要：目的探讨选择性环氧合酶2(COX-2)抑制剂塞来昔布对2型糖尿病大鼠非酒精性脂肪肝病相关的胰岛素抵抗的影响。方法雄性SD大鼠36只,随机等分为对照组、模型组、模型+塞来昔布组。造模结束前1周行胰岛素耐量试验,造模结束时(共12周)取血清、肝脏组织及附睾脂肪组织。检测血清葡萄糖、胰岛素等相关生化指标;HE染色观察肝脏和脂肪组织病理改变;Western blot检测肝脏和附睾脂肪组织中COX-2蛋白的表达。结果与对照组相比,模型组血清葡萄糖、胰岛素、总胆固醇、低密度胆固醇水平、肝内甘油三酯、肝内胆固醇水平均显著高于对照组;应用塞来昔布治疗后,上述生化指标较模型组均有显著下降。模型组胰岛素抵抗指数显著高于对照组,胰岛素敏感性指数及胰岛素耐量试验显示模型组胰岛素敏感性下降,应用塞来昔布治疗后胰岛素敏感性较模型组显著改善。模型组大鼠肝指数较模型+塞来昔布组显著升高,而模型组大鼠附睾脂肪组织质量及其相对质量(EAW/BW)显著少于模型+塞来昔布组。HE染色结果显示,模型组肝细胞脂肪变性评分显著高于对照组,应用塞来昔布治疗后模型+塞来昔布组肝细胞脂肪变性程度减轻,同时附睾脂肪组织脂肪细胞面积较模型组增加。Western blot结果显示模型组中肝组织和脂肪组织COX-2相对蛋白表达量显著高于对照组和模型+塞来昔布组。结论塞来昔布具有改善2型糖尿病大鼠非酒精性脂肪肝病相关的胰岛素抵抗作用,其机制可能与抑制肝脏组织和脂肪组织的COX-2表达有关。Objective To investigate the effect of selective COX-2 inhibitor celecoxib on the insulin resistance of non-alcoholic fatty liver disease in rots with type 2 diabetes mellitus. Methods A total of 36 male SD rats were randomly divided into control group, model group, and model＋celecoxib group （n = 12）. Insulin tolerance test （HT） was conducted at the llth week.All rats were sacrificed at the 12th week. The blood, liver and adipose tissues were collected. Related biochemical indexes including serum glucose and insulin and so on were detected. Liver and adipose tissue pathological changes were observed by HE staining. The expression of COX-2 at protein level in liver and adipose tissues were respectively detected by Western blot. Results The level of serum glucose, insulin, total cholesterol and low density cholesterol in model group were significantly higher than those in control group. The level of hepatic lxiglycerides and cholesterol in model group were significantly higher than those in control group. After the application of celecoxib, the biochemical indexes were dropped significantly in medel＋celecoxib group. Compared with control group, HOMAIR was significantly higher in the model group. Insulin sensitivity index （ISI） and ITT suggested the decreased insulin sensitivity in model group. Insulin sensitivity was significantly improved after the application of celecoxib. The liver index was higher and the EAW/BW was lower in model group compared with the model＋eelecoxib group. The HE staining results showed that hepatocyte steatosis in model group was more serious than control group. Celecoxib significantly attenuated hepatocyte steatosis and increased the adipose cells area of EAW in the model＋celecoxib group. Western blot indicated that relative COX-2 protein levels in liver and adipose tissue of the model group was significantly higher than that in control group and the model＋eelecoxib group. Conclusion Celecoxib improved the insulin resistance of non-alcoholic fatty liver disease in ty

关 键 词：塞来昔布 非酒精性脂肪肝病 胰岛素抵抗 环氧合酶2 

分 类 号：R575.5[医药卫生—消化系统]