姜黄素通过HO/GC途径对抗高糖诱导的血管收缩功能下降

目的:研究姜黄素是否可对抗高糖诱导的血管收缩功能下降,并探讨其作用机制。方法:采用血管环离体灌流装置,观察SD大鼠胸主动脉环的收缩反应;测定主动脉胆红素生成量反映血红素加氧酶-1(HO-1)的活性。结果:(1)与空白对照组(含11mmol/L葡萄糖)相比,经44mmol/L葡萄糖(高糖)孵育血管4h后,主动脉环对苯肾上腺素(PE)引起的血管收缩反应下降;(2)姜黄素(3×10-11-3×10-10mol/L)与高糖联合孵育,均能不同程度地抑制高糖诱导的血管PE收缩反应的下降;(3)姜黄素孵育后可引起血管HO活性增高;HO-1抑制剂锌原卟啉Ⅸ(ZnPP)可完全取消姜黄素的抗高糖损伤作用;(4)鸟苷酸环化酶(GC)抑制剂亚甲蓝可部分阻断姜黄素的保护作用。结论:姜黄素可能通过诱导HO-1活性增加和激活GC途径对抗高糖引起的血管收缩功能降低。

Curcumin ameliorates high glucose-induced dysfunction of vasoconstriction via heme oxygenase-1 and GC pathway

AIM: To explore the protective effect of curcumin on high glucose-induced decrease in contraction of isolated rat aortic rings, and to elucidate its underlying mechanism. METHODS: The thoracic aortic rings with endothelium of male Sprague-Dawley rats were mounted on a bath system. Isometric contractions of aortic rings were measured. HO activity was also evaluated. RESULTS: (1)Four hours after incubated with 44 mmol/L of glucose (high glucose), the vascular contraction responses to phenylephrine (PE) decreased compared to control group (containing 11 mmol/L of glucose). (2)Coincubation with curcumin (3×10-11-3×10-10 mol/L) and high glucose, the high glucose-induced decrease in contraction responses to PE of arteries was partly inhibited. (3)Four hours after incubation with curcumin, the HO activity in thoracic aorta increased. ZnPP, an inhibitor of HO-1, completely abrogated the protection effect of curcumin. (4)Methylene blue, an inhibitor of guanylate cyclase (GC), partly abolished the protective effect of curcumin. CONCLUSION: Curcumin prevents the high glucose-induced decrease in contraction responses to PE in intact aortic rings. The mechanism might be mainly involved in the activation of HO-1 and GC.