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目的:研究血管紧张素Ⅱ-2型受体(AT2)对2型糖尿病心肌病大鼠心肌细胞凋亡的影响。方法:77只雌性4周龄wistar大鼠被给予高糖高脂饮食喂养4周后形成胰岛素抵抗(IR)模型,随机抽出14只大鼠作为对照组,余作为实验组腹腔注射链脲佐菌素(STZ)。第28周末,将存活的实验组大鼠(均末次空腹血糖≥16·7mmol/L)和7只对照组大鼠(对照1组)经颈动脉插管行心脏血流动力学检测,将等容舒张期左室内压力下降的最大速率(-dp/dtmax)绝对值<5250mmHg/s的实验组大鼠中随机抽取8只(实验A亚组)与对照1组大鼠一起进行心脏重量(HW)和心肌细胞凋亡指数(CAI)检测。其余实验组大鼠被随机分为激动剂亚组(实验B亚组,8只)、拮抗剂亚组(实验C亚组,9只)和非干预亚组(实验D亚组,7只),分别腹腔内注射AT2激动剂(CGP42112A)、AT2拮抗剂(PD123319)和等量的双蒸水,均每天1次,连续4周。第32周末,检测实验B、C、D亚组与7只对照组(对照2组)大鼠的HW和CAI,逆转录聚合酶链反应法检测心肌细胞AT2和Bcl-2mRNA量,免疫组化染色法检测心肌细胞上AT2和Bcl-2蛋白质量。结果:实验A亚组-dp/dtmax绝对值明显低于对照1组(P<0·01);实验A亚组HW和CAI均明显高于对照1组(均P<0·01),且HW和CAI分别与-dp/dtmax绝对值呈正相关(均P<0·01)。实验B、C、D亚组-dp/dtmax绝对值、Bcl-2的蛋白质和mRNA表达均明显低于对照2组(均P<0·01),其中实验B亚组均明显低于实验C、D亚组(均P<0·01),实验D亚组明显低于实验C亚组(P<0·01);实验B、C、D亚组HW、CAI、AT2的mRNA量和蛋白质表达量均明显高于对照2组(均P<0·01),其中实验B组均明显高于实验C、D亚组(均P<0·01),实验D亚组明显高于实验C亚组(P<0·01)。结论:糖尿病心肌病大鼠心肌细胞AT的高表达促进心肌细胞的凋亡。
Objective: To investigate the effect of angiotensin Ⅱ type 2 receptor (AT2) on cardiomyocyte apoptosis in type 2 diabetic cardiomyopathy rats. Methods: 77 female Wistar rats, 4 weeks old, were given insulin high glucose and high fat diet for 4 weeks to form insulin resistance (IR) model. 14 rats were randomly selected as the control group. The experimental group received intraperitoneal injection of streptozotocin Prime (STZ). At the end of the 28th week, the rats in the surviving group (all the last fasting blood glucose≥16.7mmol / L) and the seven control rats (control group1) underwent cardiac hemodynamics via carotid artery cannulation Eight rats were randomly selected from experimental group (experimental A subgroup) with absolute maximum value of -dp / dtmax (-dp / dtmax) <5250mmHg / s during diastole. Heart weight ) And cardiomyocyte apoptosis index (CAI). The remaining experimental rats were randomly divided into three groups: experimental group A (experimental group B, n = 8), antagonist group (experimental group C, n = 9) and non-intervention group , Respectively, intraperitoneal injection of AT2 agonist (CGP42112A), AT2 antagonist (PD123319) and the same amount of double distilled water, once a day for 4 weeks. At the end of the 32nd week, the HW and CAI of rats in groups B, C, D and 7 control (control group 2) were detected. The amounts of AT2 and Bcl-2 mRNA in cardiomyocytes were detected by reverse transcription polymerase chain reaction The amount of AT2 and Bcl-2 protein in cardiomyocytes was detected by staining. Results: The absolute value of -dp / dtmax in experimental group A was significantly lower than that in control group 1 (P <0.01); HW and CAI in group A were significantly higher than those in control group 1 (all P <0.01) HW and CAI were positively correlated with the absolute value of -dp / dtmax (all P <0.01). The absolute value of -dp / dtmax, the protein and mRNA expression of Bcl-2 in group B, C, D were significantly lower than those in control group 2 (all P <0.01), and were significantly lower in group B than in group C , D subgroups (all P <0.01). The experimental group D was significantly lower than that of experimental group C (P <0.01). The mRNA and protein levels of HW, CAI and AT2 in group B, C and D (P <0.01). The experimental group B was significantly higher than the experimental C and D subgroups (all P <0.01), the experimental group D was significantly higher than the experimental group C Subgroup (P <0.01). Conclusion: High expression of AT in myocardial cells of diabetic cardiomyopathy promotes cardiomyocyte apoptosis.