依那普利对肾陛高血压大鼠脑缺血再灌注后脑组织基质金属蛋白酶-2、-9表达的影响

Effects of enalapril on expression of MMP-2 and MMP-9 in renal hypertension rats with focal cerebral ischemic reperfusion

目的 通过观察血管紧张素转化酶抑制剂（ACEI）依那普利对肾性高血压大鼠脑缺血再灌注后脑组织基质金属蛋白酶（MMP）-2和MMP-9表达的影响,探讨依那普利的脑保护机制.方法 Wistar雄性大鼠28只,随机分为高血压组和正常血压组.前组采用狭窄肾动脉方法建立肾性高血压大鼠模型,再随机分为依那普利组（Y）和缺血再灌注组（HIR）,分别采用依那普利2 mg/kg和0.9%氯化钠注射液进行灌胃治疗;正常血压组再分为假手术组（N）和缺血再灌注组（IR）,分别行假手术和缺血再灌注处理.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2 h,再灌注22 h.采用免疫组织化学技术检测脑组织MMP-2和MMP-9的表达,用图象分析仪测定灰度值.结果 与N组比较,IR组MMP-2、MMP-9灰度值明显增高（P＜0.01）;与IR组比较,HIR组MMP-2、MMP-9灰度值增高（P＜0.05）;与HIR组比较,Y组MMP-2、MMP-9灰度值减少（均P＜0.01）.结论 高血压加重缺血再灌注后脑组织MMP-2和MMP-9的表达;依那普利能明显抑制脑组织MMP-2和MMP-9的表达.

Objective To observe the effects of ACEI（ enalapril） on expression of MMP-2 and MMP-9 in renal hypertension rats with focal cerebral ischemia-reperfusion injury. Methods Twenty-eight Wistar male rats were randomly divided into two groups： hypertension group and normaltension group. The former which formed model of renal hypertension rats by constricted renovascular were randomly divided into enalapril group （Y） and hypertension ischemia and reperfusion group（HIR）,which fed with enalapril 2mg/kg and equal volum saline respectively;The latter were divided into sham-operation group （ N） and normaltension ischemia and reperfusion group （IR）. 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 ischemic 24h,the expression of MMP-2 and MMP-9 were measured by immunohisto-chemistry,and the gray scale value was measured by imaging analysis. Results Compared with N,the gray scale values of MMP-2 and MMP-9 in IR were higher（P 〈0. 01）; Compared with IR, the gray scale values of MMP-2 and MMP-9 in HIR were higher（P〈0. 05）;Compared with HIR,the gray scale values of MMP-2 and MMP-9 in Y were lower（P〈0.01）. Conclusion Hypertension can increase the expression of MMP-2 and MMP-9 in rats with focal cerebral ischemia-reperfusion. ACEI （Enalapril） could inhibit the expression of MMP-2 and MMP-9 in renal hypertension rats with focal cerebral ischemia-reperfusion.