Effects of rosiglitazone (PPAR γ agonist) on the myocardium in non-hypertensive diabetic rats 罗格列酮（PPAR γ 激动剂）对非高血压糖尿病大鼠的心肌的影响

• Published in: Journal of diabetes Vol. 7; no. 1; pp. 85 - 94
• Main Authors: Abou Daya, Khodor, Abu Daya, Hussein, Nasser Eddine, Mohamad, Nahhas, Georges, Nuwayri-Salti, Nuha
• Format: Journal Article
• Language: English
• Published: Blackwell Publishing Ltd 01.01.2015
• Subjects: cardiac hypertrophy; cardiovascular disease; diabetic rats; rosiglitazone; type 2 diabetes; 关键词：心血管疾病，心脏肥厚，糖尿病大鼠，罗格列酮，2型糖尿病
• ISSN: 1753-0393; 1753-0407
• DOI: 10.1111/1753-0407.12140

Background There is ongoing controversy regarding the safety of rosiglitazone and its effects on the myocardium, in some cases causing severe cardiac pathology and even in some instances mortality. In this study we aimed at examining the effects of pharmacologic doses of rosiglitazone on cardiomyocytes in diabetic non‐cardiac rats receiving sub‐optimal doses of insulin. Methods Animals were distributed into six groups: normal, diabetic, and diabetic receiving insulin, each subdivided into a control group and an experimental group receiving pharmacologic doses of rosiglitazone. Cardiomyocyte hypertrophy was assessed using heart to body weight index and microscopic examination using the number of cardiomyocytes per quadrant of high power field and intercalated disks in a sector of 100 × field. Fibrosis was assessed using Masson Trichrome staining. A number of sections of each group were stained with periodic acid Shiff and others with Sudan III for glycogen and fat accumulation, respectively. One way ANOVA was used for statistical analysis as appropriate. Results Diffuse cardiomyopathic changes in diabetic control animals were observed consisting of cardiomyocyte hypertrophy, loss of striations and widespread vacuolation. These changes were reduced and even prevented by treatment with insulin and rosiglitazone. Masson staining showed that all rat groups had no more than +1 fibrosis that is equal to what was present in the normal controls. Conclusion Rosiglitazone, in combination with even sub‐optimal doses of insulin therapy, has protective effects on cardiac muscle in diabetic animals especially those expressed as muscle hypertrophy, muscle cell death, and fibrosis. 摘要 背景：目前对罗格列酮的安全性以及它对心肌的影响仍然存在争论，在一些病例中它可导致严重的心脏病理学改变，在某些情况下甚至可以导致死亡。在这项研究中，我们的目的是在接受不是最佳剂量的胰岛素治疗的无心脏病的糖尿病大鼠中调查药理剂量的罗格列酮对心肌细胞的影响。 方法：动物被分成6组：正常组、糖尿病组、接受胰岛素治疗的糖尿病组，上述3组每组再分为对照组与接受药理剂量罗格列酮治疗的试验组。使用心脏占体重的指数来评估心肌细胞肥大，并且使用显微镜检查了每四分之一高倍视野下的心肌细胞数量以及100×视野下一个扇区内的闰盘数量。使用Masson三色染色法来评估纤维化。对每组的多个切片使用高碘酸Shiff和苏丹III进行染色来观察糖原与脂肪蓄积。使用相匹配的单因素方差分析法进行统计分析。 结果：在糖尿病对照组的动物中观察到了弥漫性的心肌病理变化，包括心肌细胞肥大，肌纹消失以及广泛的空泡化。经过胰岛素与罗格列酮的治疗后这些病理变化减少了甚至得到了预防。使用Masson染色后发现所有分组的大鼠的纤维化程度都不超过+1，这与正常对照组相比是一样的。 结论：糖尿病动物使用罗格列酮联合即便不是最佳剂量的胰岛素治疗后对心肌具有保护作用，特别是那些表现为肌肉肥大、肌细胞死亡以及纤维化的心肌病变。