蛋白酪氨酸激酶与糖尿病大鼠主动脉平滑肌高反应性的关系

Role of protein tyrosine kinase in hyperreactivity of aortic smooth muscle from exeperimental diabetic rats

目的 探讨蛋白酪氨酸激酶在糖尿病大鼠主动脉平滑肌高反应性中的作用。方法 离体主动脉环张力实验。结果 在 8～ 10wk的糖尿病大鼠 :①主动脉平滑肌对苯肾上腺素的浓度依赖性收缩反应显著增加 ,最大收缩反应为( 167± 2 3 ) g·g-1组织净重 ,较对照组 ( 10 0± 17) g·g-1组织净重增加了约 67% ,②蛋白酪氨酸磷酸酶抑制剂sodiumor thovanadate的浓度依赖性收缩反应也明显增强 ,1mmol·L-1sodiumorthovanadate的收缩反应为 ( 2 0 8± 2 5 )g·g-1组织净重 ,较对照组 ( 113± 18) g·g-1组织净重增加了约 85 % ,③蛋白酪氨酸激酶抑制剂 genistein均浓度依赖性地抑制糖尿病组和对照组主动脉平滑肌对苯肾上腺素的收缩反应 ,但在对照组的抑制率显著大于糖尿病组。结论 糖尿病大鼠主动脉平滑肌的高反应性可能与糖尿病时蛋白酪氨酸激酶的活性增加有关。

AIM To investigate whether the hyperreactivity of aortic smooth muscle from diabetic rats is associated with protein tyrosine kinase activity. METHODS The changes of tension of aortic rings were recorded in vitro . RESULTS In aortic smooth muscles from diabetic rats 8～10 weeks after ip streptozotocin(STZ): ①Contractitle responses to phenylephrine were significantly enhanced in diabetic rats compared with age matched controls.The maximal response increased by approximately 67%, in diabetic group: 167±23 vs control: 100±17; ②Sodium orthovanadate induced contractile responses were also significantly enhanced in diabetic rats compared with age matched controls, the tension to 1 mmol·L -1 sodium orthovanadate increased by about 85%,in diabetic group:208±25 vs control: 113±18; ③Genistein, a tyrosine kinase inhibitor, inhibited the contractile responses to phenylephrine in aortic smooth muscles both from diabetic rats and age matched controls, but the inhibitory effects on diabetic rats were significantly reduced. CONCLUSION The hyperreactivity of aortic smooth muscles from diabetic rats is probably associated with increased activity of protein tyrosine kinase.