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目的:通过观察血管紧张素Ⅱ受体拮抗剂(Angiotensin receptor blocker,ARB)对肾性高血压大鼠脑缺血再灌注后脑组织中基质金属蛋白酶-2(Matrix metalloproteinase-2,MMP-2)和基质金属蛋白酶-9(Matrix metalloproteinase-9,MMP-9)表达的影响,探讨ARB的脑保护机制。方法:将Wistar雄性大鼠32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,再随机分为高血压缺血再灌注组(Hypertension ischemic reperfusion,HIR)和HIR缬沙坦组(G),分别采用生理盐水和缬沙坦12mg/kg进行灌胃治疗4周;正常血压组分为假手术组(N)和缺血再灌注组(Ischemic reperfusion,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,G组MMP-2、MMP-9灰度值减少(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;ARB能明显抑制脑组织MMP-2和MMP-9的表达。
OBJECTIVE: To investigate the effects of angiotensin receptor blocker (ARB) on the expression of matrix metalloproteinase-2 (MMP-2, MMP-2, Matrix metalloproteinase-9 (MMP-9) expression, to explore the protective mechanism of ARB. Methods: 32 Wistar male rats were randomly divided into hypertensive group and normotensive group. In the former group, renal hypertensive rat models were established by the method of narrowing the renal artery and then randomly divided into Hypertension ischemic reperfusion (HIR) group and HIR valsartan group (G) Shantan at 12 mg / kg for 4 weeks. The normotensive subjects were sham-operated group (N) and Ischemic reperfusion group (IR). Sham operation and ischemia-reperfusion were performed respectively. Cerebral ischemia-reperfusion model was induced by middle cerebral artery occlusion. The ischemia time was 2 hours and the reperfusion time was 22 hours. Immunohistochemistry was used to detect the expression of MMP-2 and MMP-9 in brain tissue, and the gray value was measured by image analyzer. Results: The gray value of MMP-2 and MMP-9 in IR group was significantly higher than that in N group (P <0.01). Compared with IR group, the gray value of MMP-2 and MMP- Compared with HIR group, the gray value of MMP-2 and MMP-9 in G group decreased (P <0.01). Conclusion: Hypertension can increase the expression of MMP-2 and MMP-9 in brain tissue after ischemia-reperfusion. ARB can significantly inhibit the expression of MMP-2 and MMP-9 in brain tissue.