糜蛋白酶活性与链脲菌素诱导糖尿病仓鼠心肌病变的研究  

Experimental study on the relationship between chymase activity and cardiomyopathy in STZ-induced diabetic hamsters

作　　者：赵柯湘[1] 肖谦[1] 黄昶荃[1] 牛桂芬[1] 

机构地区：[1]重庆医科大学附属第一医院老年病科内分泌组,重庆400016

出　　处：《中华老年心脑血管病杂志》2007年第1期49-52,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：重庆市自然科学基金资助项目(2005BB5274)

摘　　要：目的通过观察链脲菌素(STZ)诱导糖尿病仓鼠心肌病变中糜蛋白酶(chymase)的活性变化,探讨chymase在糖尿病仓鼠心肌病变形成中的作用及机制。方法20只8周龄雌性仓鼠,随机分为对照组10只,糖尿病组10只,腹腔注射STZ 40 mg/d,连续3天,诱导实验性1型糖尿病仓鼠模型,成模后18周,电镜观察心肌超微结构的改变,链霉素-亲和素-生物素-过氧化物酶复合物法检测心肌Ⅰ、Ⅲ型胶原水平,原位末端标记法检测心肌细胞凋亡。放射免疫分析法测定心肌chymase及血管紧张素转换酶活性、血管紧张素Ⅱ(AngⅡ)含量。结果(1)与对照组比较,糖尿病组仓鼠血糖、血脂明显升高,心肌细胞线粒体肿胀明显,局部破裂,肌丝广泛溶解,核肿胀,Ⅰ、Ⅲ型胶原沉积、心肌细胞凋亡明显。(2)糖尿病仓鼠心肌chyamse活性(0.88±0.07)U/mg组织较对照组(0.54±0.04)U/mg组织明显升高(P<0.01),而血管紧张素转换酶活性无明显差异,分别为(0.72±0.11)U/mg组织和(0.66±0.13)U/mg组织;糖尿病仓鼠心肌AngⅡ含量(95.8±16.0)pg/mg组织较正常对照组(51.1±20.8)pg/mg组织明显升高(P<0.01)。结论糖尿病心肌病变的仓鼠心肌中,chymase活性明显升高,并伴随心肌局部AngⅡ含量的升高。Objectives To investigate the activity of chymase in the cardiomyopathy of streptozotocin-induced diabetic hamsters, to explore the relationship between the activity of chymase and the angiotensin Ⅱ. Methods 8-month-old female hamsters were randomly divided into the control group（ n = 10） and the diabetes（DM） group（ n = 10）. The myocardial ultrastructure was observed with electron microscope and pathologic changes were observed with microscope. Immunohistochemlstry was used to measure the levels of expression of type- Ⅰ and type-Ⅲ collagen in diabetic and normal hamster hearts. Apoptosis of cardiomyocyte was measured using TUNEL method. Radioimmunuoassay method was used to determine the level of angiotensin Ⅱ and the activity of chymase and ACE. Results Compared with the control group, levels of blood glucose, TG, TC and LDL in DM group were much higher. Levels of expression of collagen Ⅰ and Ⅲ in DM group were much higher than those in the control group. Chymase activity in DM group was much higher than that in the control group （0.88 ± 0.07 U/mg tissue vs 0. 54 ±0.04 U/mg tissue）, but the activity of ACE was unchanged （0.72 ± 0.11 U/mg tissue vs 0. 66 ± 0.13 U/mg tissue）. The level of angiotensin Ⅱ in DM group was much higher than that in the control group （95.8 ± 16.0 pg/mg tissue vs 51.1 ± 20.8 pg/mg tissue）. Conclusion In diabetic hamstets, the activity of chymase was much higher than in the control group, accompanying higher level of angiotensin Ⅱ , higher levels of expression of collagen Ⅰ and Ⅲ.

关 键 词：糖尿病 糜蛋白酶 链脲菌素 心肌疾病 仓鼠 

分 类 号：R587.2[医药卫生—内分泌]