【摘要】 目的 探讨模拟急进高原环境对糖尿病大鼠心肌损伤的影响及机制。方法 采用雄性Wistar大鼠建立2型糖尿病大鼠模型，依据模拟急进不同海拔高原环境，采用随机数字表法将50只大鼠分为5组：空白对照组（C组）、3 700 m正常组（C37组）、5 000 m正常组（C50组）、3 700 m糖尿病组（D37组）、5 000 m糖尿病组（D50组）。对大鼠进行心电图检查、动脉血气分析及血清心肌酶谱检测；并取心肌病理标本进行HE、PAS、TUNEL染色，观察形态学变化及细胞凋亡情况；利用lncRNA芯片技术检测大鼠心肌组织lncRNA表达谱的差异，筛选出差异表达的lncRNA。结果 D37组大鼠心电图可见频发室性早搏，D50组大鼠可见ST段压低、T波改变；血气分析显示，与C组、C37组和C50组比较，D37组和D50组大鼠的pH值和PaO2均显著下降（P<0.05），肌酸激酶同工酶MB(CK-MB)水平升高（P<0.05）;D37组和D50组心肌形态学检查可见心肌细胞肥大、糖原物质大量沉积，细胞凋亡比例增高，D50组伴有炎性细胞浸润；心肌lncRNA芯片分析发现，D37组与C37组、D50组与C50组差异表达lncRNA的功能主要集中在调控α1-肾上腺素受体、肌动蛋白活性和压力诱导的心肌肥大。mRNA差异基因KEGG富集分析显示，参与肥厚性心肌病、扩张性心肌病、心肌收缩等信号通路的Myh6、Myh7、Actc1等基因参与了心肌损伤的过程。结论 糖尿病大鼠在急进高原状态时心肌细胞凋亡增加，同时激活了诱导心肌细胞肥大的相关基因，较正常大鼠更容易出现心肌损伤。更多还原

【Abstract】 Objective To explore the effect of simulated rapidly entering plateau environment on myocardial injury in diabetic rats and its mechanism.Methods Male Wistar rats were used to establish the rat model of type 2 diabetes mellitus,and 50 rats were divided into5 groups with the random number table method according to the simulated rapidly entering plateau environment of different altitudes: the blank control group(C group),the 3 700 m normal group(C37 group),the 5 000 m normal group(C50 group),the 3 700 m diabetic group(D37 group),and the 5 000 m diabetic group(D50 group). The rats were subjected to electrocardiogram,arterial blood gas analysis and serum myocardial enzymes detection. The pathological specimens of myocardium were stained with HE,PAS and TUNEL to observe the morphological changes and cell apoptosis. lncRNA microarrays was used to detect the difference of lncRNA expression profile in rat myocardial tissue,and the differentially expressed lncRNA was screened out.Results Frequent ventricular premature beats were observed in rats of the D37 group,and ST segment depression and T wave changes were observed in rats of the D50 group. The blood gas analysis showed that compared with the C group,the C37 group and the C50 group,the pH value and PaO2of the rats in the D37 group and the D50 group were significantly decreased(P< 0. 05),while the creatine kinase-MB( CK-MB) levels were increased(P< 0. 05). The morphological examination of myocardium showed that cardiomy cyte hypertrophy,glycogen deposition,and increased proportion of cell apoptosis were observed in the D37 group and the D50 group,and inflammatory cell infiltration was observed in the D50 group. Myocardial lncRNA microarray analysis revealed that the functions of differentially expressed lncRNA between the D37 group and the C37 group,the D50 group and the C50 group were mainly focused on the regulation of α1-adrenergic receptors,actin activity and stress-induced myocardial hypertrophy. KEGG enrichment analysis of mRNA differential genes showed that Myh6,Myh7,Actc1 and other genes involved in hypertrophic cardiomyopathy,dilated cardiomyopathy,myocardial contraction and other signaling pathways were involved in the process of myocardial injury.Conclusion The apoptosis of myocardial cells is increased in diabetic rats when they rapidly entering the plateau environment,and the genes related to cardiomyocyte hypertrophy are activated at the same time. Diabetic rats are more prone to myocardial injury than normal rats.更多还原