论文部分内容阅读
目的:通过观察血管紧张素Ⅱ受体拮抗剂(ATⅡRA)对肾性高血压大鼠脑缺血再灌注后脑组织核转录因子-κBp65(NF-κBp65)和基质金属蛋白酶-9(MMP-9)表达的影响,探讨ATⅡRA的脑保护机制。方法:Wistar雄性大鼠80只,随机分为高血压组和正常血压组。高血压组采用狭窄肾动脉方法建立肾性高血压大鼠模型,再随机分为缬沙坦大剂量组(GB)、缬沙坦小剂量组(GM)和缺血再灌注组(HIR),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;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2h,再灌注22h。采用免疫组化技术检测脑组织NF-κBp65和MMP-9的表达,用图像分析仪测定灰度值。结果:脑缺血再灌注后NF-κBp65和MMP-9表达的情况为:GB组、GM组与HIR组比较,NF-κBp65、MMP-9灰度值明显减小(P<0.01,P<0.05,P<0.01),与IR组比较灰度值减小(P<0.05)。结论:高血压通过增加NF-κBp65和MMP-9的表达,加重缺血再灌注后脑损伤。ATⅡRA均能明显抑制脑组织NF-κBp65和MMP-9的表达,提示此抗高血压药均对脑缺血再灌注损伤有脑保护作用;缬沙坦的上述作用与剂量有关。
Objective: To observe the effects of angiotensin Ⅱ receptor antagonist (ATⅡRA) on the expression of nuclear factor-κBp65 and MMP-9 in rat with renal hypertension after cerebral ischemia / Expression of the impact of AT Ⅱ RA brain protection mechanism. Methods: Eighty Wistar male rats were randomly divided into hypertensive group and normotensive group. Hypertension group was established by renal artery stenosis model of renal hypertension, and then randomly divided into high-dose valsartan group (GB), valsartan low-dose group (GM) and ischemia-reperfusion group (HIR) Valsartan 6mg / kg and normal saline were given respectively. The normal blood pressure group was further divided into sham operation group (N) and ischemia reperfusion group (IR) Ischemia reperfusion treatment. Cerebral ischemia-reperfusion model was induced by middle cerebral artery occlusion. The ischemia time was 2h and reperfusion was performed for 22h. Immunohistochemistry was used to detect the expression of NF-κBp65 and MMP-9 in brain tissue, and the gray value was measured by image analyzer. Results: The expression of NF-κBp65 and MMP-9 in cerebral ischemia-reperfusion group was significantly lower than that in GB group and GM group (P <0.01, P < 0.05, P <0.01). Compared with IR group, gray value decreased (P <0.05). Conclusion: Hypertension increases brain injury after ischemia-reperfusion by increasing the expression of NF-κBp65 and MMP-9. ATⅡRA can significantly inhibit the expression of NF-κBp65 and MMP-9 in brain tissue, suggesting that this antihypertensive drugs have cerebral protection against cerebral ischemia-reperfusion injury; valsartan above-mentioned dose-related.