类胰蛋白酶与2型糖尿病心肌病发病机制  

Tryptase and the mechanism of type 2 diabetic cardiomyopathy

作　　者：赵娅[1] 刘飞[1] 古远云[2] 李程[1] 徐勇[1] 万沁[1] 

机构地区：[1]泸州医学院附属医院内分泌科,泸州646000 [2]泸州医学院附属中医医院综合老年病科,泸州646000

出　　处：《重庆医科大学学报》2015年第7期997-1000,共4页Journal of Chongqing Medical University

基　　金：国家代谢性疾病临床医学研究中心资助项目(编号:2013BAI09B13);科技部重大新药创制资助项目(编号:2012ZX09303006-001)

摘　　要：目的:通过研究类胰蛋白酶对2型糖尿病心肌病建模成功的Wistar大鼠的影响及可能机制,为进一步治疗糖尿病心肌病提供理论依据。方法:45只雄性Wistar大鼠随机分为3组:正常对照组(NC组,15只)、2型糖尿病心肌病组(DCM组,15只)、类胰蛋白酶抑制剂组(干预组,15只)。后2组通过高脂高糖饮食加一次性腹腔注射链脲佐菌素诱导建立糖尿病心肌病大鼠模型,建模成功后,干预组每只大鼠给予0.025%的酮替芬溶液1 mg/kg腹膜腔内注射,2次/d,连续注射8周,NC和DCM两组给予等体积的生理盐水。实验结束后处死全部大鼠,称取体质量、全心重、左心室重量,测定全心指数和左心室重量指数,在光镜下对各组心肌组织进行观察分析,用ELISA检测各组大鼠血清肿瘤坏死因子(tumor necrosis factor,TNF-α),采用Western blot方法测定各组大鼠左心室心肌组织类胰蛋白酶蛋白表达量。结果:全心指数和左心室重量指数:DCM组全心指数及左心室重量指数明显高于NC组(P<0.05),干预组全心指数及左心室重量指数低于DCM组(P<0.05)。常规HE染色结果显示:与NC组比较,DCM组心肌组织病理变化可见明显的心肌纤维排列紊乱、断裂,心肌细胞肥大,细胞核边缘不清;干预组心肌细胞体积较DCM组有不同程度的缩小,心肌细胞排列规则,断裂现象少见,细胞核大小尚均一。大鼠血清TNF-α水平:DCM组显著高于NC组(P<0.05),干预组低于DCM组(P<0.05)。类胰蛋白酶相对灰度值比较:DCM组高于NC组(P<0.05),干预组低于DCM组(P<0.05)。结论:2型糖尿病大鼠心肌组织存在类胰蛋白酶的表达增强,经类胰蛋白酶抑制剂干预后糖尿病心肌病大鼠模型心肌病理改变减轻,类胰蛋白酶的表达降低。类胰蛋白酶表达的增强可能参与糖尿病心肌病的发生。Objective：To study the effect of tryptase on Wistar rats in type 2 diabetic cardiomyopathy model and to provide theoretical basis for the further treatment of diabetic cardiomyopathy. Methods：Totally 45 male Wistar rats were randomly separated into 3 groups：normal control（NC） group,type 2 diabetic cardiomyopathy（DCM） group and trypsin inhibitor groups（intervention group）. The rats of DCM and intervention group received intrapperitioneal injection of streptozotocin after high fat and high glucose breeding to form an experimental model of diabetes cardiomyopathy. The rats of intervention group received 0.025% ketotifen solution 1 mg/kg twice a day by hypodermic injection. Rats in NC and DCM groups were given injection of physiological saline. After the experiment,all the rats were sacrificed. Body,all heart,left ventricular were weighted to calculate all heart and left ventricle weight index. Myocardial tissue was observed under the light microscopy;serum tumor necrosis factor-α（TNF-α） was tested by ELISA;trypsin protein expression in rats of left ventricular myocardial tissue was examined by Western blot. Results：All heart and left ventricle weight index of DCM group was significantly higher than that of NC group（P0.05）. All heart and left ventricle weight index of intervention group was lower than that of DCM group（P0.05）. Routine HE staining results showed that,compared with those of NC group,myocardial tissue pathological changes were more visible in DCM group：disordered arrangement of cardiac muscle fiber fracture,myocyte hypertrophy,apoptosis,uncleared cell nucleus edge. Myocardial cell volume was narrowed in DCM group than in intervention group;in intervention group,myocardial cell arranged regularly with rare fracture and similar nucleus size. Serum TNF-α was significantly higher in DCM group than in NC group（P0.05）. TNF-α was lower in intervention group than in DCM group. Tryptase relative grey value was higher in DCM group than in NC group（P0.05）. Tryptase rel

关 键 词：糖尿病心肌病 类胰蛋白酶 酮替芬 

分 类 号：R587.2[医药卫生—内分泌]