苯肾上腺素对糖尿病大鼠室性心律失常的诱导作用

Induced effect of phenylephrine on ventricular arrhythmia in diabetic rat

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。

Aim To compare the differential effects of α1 adrenoceptor （α1-AR） on ventricular arrhythmia and early afterdepolarization （EAD） on left ventricular myoeytes 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 （1000μmol · 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.