1,6二磷酸果糖下调血管紧张素Ⅱ受体2表达保护糖尿病大鼠心肌  

Fructose-1,6-Diphosphate Protects STZ-induced Diabetic Rat from the Cardiomyopathy by Down-regulating Angiotensin Ⅱ Type 2 Receptor Expression

作　　者：李长运[1] 曹林生[1] 白智峰[1] 毛晓波[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院心内科,武汉430022

出　　处：《华中科技大学学报（医学版）》2005年第2期206-209,213,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

摘　　要：目的　研究血管紧张素Ⅱ受体2型(AT2) 及1, 6 -二磷酸果糖对糖尿病大鼠心肌细胞凋亡的影响。方法建立Wistar大鼠2型糖尿病心肌病模型。将等容舒张期左室内压下降的最大速率(-dp/dtmax) ≤700 mmHg/s的糖尿病大鼠(24只) 分组: 糖尿病对照组(7只), 用等量的双蒸水腹腔注射; AT2 激动剂组(8 只), 腹腔注射AT2激动剂(CGP42112A); 果糖组(9只), 腹腔注射1, 6二磷酸果糖。另设胰岛素抵抗组(7 只), 仅给予等量枸橼酸钠缓冲液(pH=4. 5) 腹腔注射。以上注射每天1次连续4周。记录心脏重量, 通过凋亡试剂盒检测心肌细胞凋亡指数, 逆转录聚合酶链反应法(RT- PCR) 检测心肌细胞AT2 和bcl- 2 mRNA量, 免疫组化染色法检测心肌细胞AT2和Bcl -2蛋白表达量。结果　AT2激动剂组、果糖组和糖尿病对照组的-dp/dtmax分别显著低于胰岛素抵抗组(均P<0 .01), 而心肌细胞凋亡指数、AT2的mRNA量和蛋白质表达量及心脏重量却分别显著高于胰岛素抵抗组(均P<0 .01); 心肌细胞凋亡指数及AT2 的mRNA量和蛋白质表达量AT2 激动剂组>糖尿病对照组>果糖组(均P<0 01); 各组Bcl 2变化正好与AT2变化相反。结论　AT2高表达促进糖尿病大鼠心肌细胞的凋亡, 是糖尿病心肌病的重要促发因素之一, 1, 6-二磷酸果糖通过下调AT2表达保护糖尿病大鼠心?Objectives To study the potential roles of angiotensin Ⅱ type 2 receptor (AT_ 2) and Fructose-1,6-Diphosphate (FDP) in rats with STZ-induced diabetic cardiomyopathy.Methods Wistar rat type 2 diabetic cardiomyopathy model was made. Twenty-four diabetic cardiomyopathy rats with -dp/dt_ max (the maximal velocity decrease of pressure per second in left ventricle within the period of isovolumic relaxation)≤700 mmHg/s were divided into following groups: diabetic control group (n=7) was treated with double distilled H_ 2O (i.p); AT_ 2 agonist group (n=8) was treated with AT_ 2 agonist (CGP42112A) (i.p). FDP group (n=9) was treated with Fructose-1,6-Diphosphate. In addition,insulin group (n=7) was treated with sodium citrate buffer (pH=4.5). All injections lasted 4 weeks (once every day) and the heart weight (HW) was recorded. The cardiomyocyte apoptosis index (CAI),the expression levels of AT_ 2 and Bcl-2 mRNA and protein in cardiomyocytes were measured by methods of terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL),reversal transcription polymerase chain reaction (RT-PCR) and immunoblot (Western blot) respectively.Results Values of -dp/dt_ max in AT_ 2 agonist group,FDP group and diabetic control group were much less than those in insulin group (P<0.01). CAI and AT_ 2 values both in mRNA and protein levels in insulin group were less than those in the other three groups and were more in AT_ 2 agonist group but less in FDP group than those in control group,respectively (P<0.01). CAI,the expression of AT_ 2 mRNA and protein and HW in AT_ 2 agonist group were much higher than in FDP group (P<0.01). The changes of Bcl-2 were opposed to those of AT_ 2.Conclusion High expression of AT_ 2 might accelerate the apoptosis of cardiomyocytes in diabetic rats and play a great role in precipitating diabetic cardiomyopathy. Fructose-1,6-Diphosphate can protect STZ-induced diabetic rats from the cardiomyopathy by downregulating the expression of AT_ 2.

关 键 词：糖尿病心肌病 血管紧张素Ⅱ受体2型激动剂 1 6二磷酸果糖 细胞凋亡 

分 类 号：R287.2[医药卫生—中药学]