ARB对肾性高血压大鼠脑缺血再灌注后NOS的影响

目的通过观察血管紧张素Ⅱ受体拮抗剂（ARB）对肾性高血压大鼠脑缺血再灌注后神经功能、细胞凋亡和NOS的影响，以探讨ARB的脑保护机制。方法Wistar雄性大鼠采用狭窄肾动脉方法建立肾性高血压大鼠模型，随机分为缬沙坦大剂量组（VB组）、缬沙坦小剂量组（VS组）、对照组（C组），分别采用缬沙坦12mg／kg、缬沙坦6mg／kg和生理盐水进行灌胃治疗4周；采用大脑中动脉线栓法造成大脑缺血再灌注模型，缺血时间为2h，再灌注24h，假手术组（N组）作为空白对照。进行神经功能评分后取脑，采用免疫组织化学技术检测脑组织eNOS、iNOS、nNOS的表达，TUNLE法检测脑细胞凋亡情况。结果缬沙坦大剂量组和小剂量组大鼠的神经功能评分显著低于对照组（P〈0．05，P〈0．05），细胞凋亡显著低于对照组（P〈0．05，P〈0．05），eNOS表达水平显著高于对照组（P〈0．05，P〈0．05），nNOS和iNOS表达显著低于对照组（P〈0．05，P〈0．05）；缬沙坦大剂量组细胞凋亡显著低于小剂量组（P〈0．05），eNOS表达水平明显高于小剂量组（P〈0．05），nNOS、iNOS表达水平明显低于小剂量组（P〈0．05）。结论ARB能明显改善局灶性脑缺血大鼠的神经功能，减少细胞凋亡，上调脑组织eNOS的表达，抑制nNOS、iNOS表达，提示对脑缺血-再灌注损伤有脑保护作用，上述作用可能具有剂量依赖性。

The effect of ARB to NOS for the renal hypertension rats with injured of focal cerebral isehemiare-perfusion

Objective To study the protective mechanism of ARB through observed the ARB （valsartan ） on NOS in renal hypertension rats with injured of focal cerebral ischemia-reperfusion. Methotis Wistar male rats were founded the model of renal hypertension by constricted renal artery. They were divided randomly into Valsartan group in great dose （VB）, Valsartan group in small dose （VS）, and hypertension ischemia and reperfusion control group （C）. The rats were feed with Valsartan 12mg/kg, 6mg and equal volume physiological saline respectively. The focal cerebral ischemia model was established in Wistar rats by using the method of thread inserting left middle cerebral artery occlusion （MCAO） for 2h. After ischemie-reperfusion 24h, neurological evaluation was carried out and brains were take out. The expression of eNOS, iNOS and nNOS were measured by immunohistochemistry, and the apoptosis of cell was analyzed by TUNEL. Results The neurological evaluation and the number of apoptosis about the VB and VS was lower than the control group （P〈0. 05, P〈0. 05 respectively）, the number of apoptosis were lower. On the other hand, the expression of eNOS for the VB and VS were higher, and the expression of iNOS and nNOS were lower than control group （P〈 0. 05, P〈0. 05 respectively）. Compared with VS, the number of apoptosis were lower, the expression of eNOS were higher and the expression of iNOS, nNOS were lower in VB （P〈0. 05, P〈0. 05, respectively）. Conclusion ARB （Valsartan） can improve the neurological function, reduce the apoptosis, up-regulate the expression of eNOS, and inhibit the expression of nNOS and iNOS in rats with injured of the focal cerebral ischemia-reperfusion. It is showed that ARB has the protective effect to the injured of cerebral ischemia-reperfusion.