苯肾上腺素对糖尿病大鼠室性心律失常的诱导作用

目的比较α1肾上腺素受体(α1-AR)激动剂苯肾上腺素对正常及链脲霉素(STZ)诱导的糖尿病大鼠室性心律失常的差异作用,及对两组大鼠左心室肌细胞早期后除极(EAD)的差异作用;并分析两组大鼠左心室α1-AR各亚型的差异表达,解析其可能的物质基础。方法采用离体心脏心电图及电流钳法,分析α1-AR激动剂(苯肾上腺素,PE)诱导正常和糖尿病大鼠离体心脏心律失常发生率及左心室肌细胞EAD发生率的差异作用。采用Westernblot法,比较两组大鼠左心室α1-AR各亚型的蛋白表达。结果与正常大鼠相比,PE(100μmol.L-1)诱导糖尿病大鼠离体心脏产生室性心律失常的机率明显增加,PE(1000μmol.L-1)诱导左心室肌细胞产生EAD的机率明显增加;α1A-AR在糖尿病大鼠左心室的表达明显增加。结论α1-AR激动剂使糖尿病大鼠左心室肌细胞产生高机率的EAD是其诱导高机率室性心律失常的基础。而糖尿病大鼠左心室α1A-AR表达明显增加是其物质基础。

Induced effect of phenylephrine on ventricular arrhythmia in diabetic rat

Aim To compare the differential effects of α1 adrenoceptor(α1-AR) on ventricular arrhythmia and early afterdepolarization(EAD) on left ventricular myocytes in normal and streptozocin(STZ) induced diabetic rats.To measure the differential expressions of α1-AR subtypes in two group rat ventricles.Methods Experimental diabetes was induced in rats following a single injection of STZ and the heart and cardiac myocytes were isolated after 4 weeks.Isolated heart ECG techniques and whole-cell patch clamp of cardiac myocytes were used to study rat ventricular arrhythmias and EAD in rat ventricular myocytes.Western blot method was used to measure the expression of α1-AR subtype proteins in the left ventricles of the rat hearts.Results Compared to normal rats,phenylephrine(PE,100 μmol·L-1),an α1-AR agonist,significantly induced a greater magnitude of ventricular arrhythmias in isolated diabetic hearts.At a higher dose,PE(1000 μmol·L-1) significantly induced a greater magnitude of the EAD in ventricular myocytes of diabetic rats.This was correlated with a greater expression of α1A-AR subtype receptor protein in diabetic rat ventricles as compared to normal rat ventricles.Conclusions In diabetic hearts,the mechanism underlying the great magnitude of ventricular arrhythmia induced by PE is due to a PE induced significantly greater magnitude EAD in ventricular myocytes.The overexpression of α1A-AR on diabetic ventricles mediates the above effects.