二甲双胍对糖尿病大鼠心肌保护作用的形态学观察

Morphological observation on the protective effect of metformin on myocardium of diabetic rats

目的:观察传统的降糖药二甲双胍对糖尿病大鼠心肌的保护作用。方法:实验于2004-03/10在锦州医学院试验动物中心完成。①取雄性SD大鼠一次性尾静脉注射新鲜配置的20g/L链脲佐菌素溶液60mg/kg制备糖尿病模型,取造模成功(空腹血糖≥13.9mmol/L)大鼠50只单纯随机分为糖尿病组10只,胰岛素组和二甲双胍组各20只,另取10只尾静脉注射枸橼酸钠缓冲液的正常大鼠为正常对照组。②成模后第4天起,糖尿病组隔天皮下注射鱼精蛋白胰岛素1～2U/次维持存活,胰岛素组皮下注射普通胰岛素(4～6U/次,每天两三次),二甲双胍组灌胃二甲双胍20～30mg/(kg·d),正常对照组每天灌胃等量生理盐水。实验过程中胰岛素组和二甲双胍组大鼠空腹血糖控制在6.4mmol/L以下。③治疗12周后,大鼠断头处死,采血测血糖和血浆胰岛素,取左心室心肌组织,常规制作电镜切片,JEOL1200EX电子显微镜观察。结果:60只大鼠进入结果分析。①空腹血糖水平:胰岛素组和二甲双胍组显著低于糖尿病组[(7.84±3.6),(8.16±3.13),(14.00±4.00)mmol/L,P<0.05],与正常对照组比较差异不显著[(5.76±0.84)mmol/L,P>0.05]。②空腹血浆胰岛素水平:二甲双胍组与正常对照组比较差异不明显[(11.01±4.21),(9.48±3.56)mU/L,P>0.05],但低于胰岛素组和糖尿病组[(33.86±14.73),(23.39±13.85)mU/L,P<0.05]。③心肌超微结构:糖尿病组大鼠心肌纤维内肌节紊乱,肌原纤维变性,线粒体增多,常有肿胀变性。经二甲双胍和胰岛素治疗后糖尿病大鼠心肌超微结构病理改变明显减轻。结论:二甲双胍能抑制糖尿病大鼠的心肌病变,对心肌有良好的保护作用。

AIM： To observe the protective effect of traditional glucose-reduced drug metformin on myocardium in diabetic rats. METHODS： The experiment was conducted in the Central Laboratory for Experimental Animals, Jinzhou Medical College from March to October 2004. ①The model of diabetes was established with 20 g/L streptozotocin （STZ） solution 60 mg/kg into vena caudalis of male SD rats. Fifty successfully modeling rats （fasting blood glucose ≥ 13.9 mmol/L） were randomly divided into diabetic group （n =10）, insulin group （n =20）, mefformin group （n =20） and normal group with another 10 normal rats after injection of natrium citricum buffer solution. ②Since the 4th day after modeling, the rats in the diabetic group ware injected with protamine zinc insulin 1-2 U every time to keep living every two days; the rats in the insulin group ware injected normal insulin （4-6 U every time, twice to three times daily）; the mefformin group was intragastrically infused with metformin 20-30 mg/kg daily; the normal control group was infused matching normal saline. The fasting blood sugar of the insulin and metformin groups was kept below 6.4 mmol/L during experiment. ③After 12 weeks treatment, the blood sugar and insulin were measured after killed the rats. The thin section of left ventricular myocardium was observed by JEOL1200EX electron microscope. RESULTS： All the 60 rats were involved in the result analysis. ①Fasting blood sugar level： The level of the insulin and metformin groups were markedly lower than the diabetic group [（7.84±3.6）, （8.16±3.13）, （14.00±4.00） mmol/L, P 〈 0.05], and there was no significant difference compared with the normal control group [（5.76±0.84） mmol/L, P 〉 0.05]. ② Fasting insulin level： No significant difference was found in the mefformin and normal control groups [（11.01±4.21）, （9.48±3.56） mU/L, P〉 0.05], but the metformin group was lower than the insulin and diabetic groups [（33.86±14.73）, （23.39±13.85） mU/L, P〈 0.05]. ③Myocardial ultrastructure： Myocomma derangement and myofibrillar degeneration were observed in the diabetic group. Transmission electron microscope revealed marked increasing and swelling of the mitochondria. The changes of myocardial ultrastructure were obviously lightened after treatment with metfromin and insulin. CONCLUSION： Metformin can effectively reduce myocardium damage and protect cardiac myocytes of rats with diabetes mellitus.