SHR大鼠脑出血急性期氨氯地平血压干预和血肿周围水肿的相关性研究

Correlation between the potential mechanism of edema around the hematoma and antihypertensive therapy in spontaneously hypertensive rats

目的采用自发性高血压大鼠(SHR)脑出血模型,研究脑出血后急性期血压和血肿周围水肿的相关性。方法胶原酶法制备SHR大鼠脑出血模型,出血部位为右侧基底节区。动物随机分为脑出血组、脑出血常规剂量氨氯地平降压组、脑出血强化剂量氨氯地平降压组。MRI检查并计算血肿周围水肿大小;免疫组化及荧光定量PCR法检测血肿周围水肿的AQP4表达。结果 (1)氨氯地平治疗组MRI检测值显示,脑血肿周围水肿减轻,降压组均优于未干预组,强化降压组优于常规降压组,差异有统计学意义,第3、5、7天的F值分别为16.987、35.448、37.174(P<0.05);收缩压降低幅度和血肿周围水肿体积之间有相关性,在第3、5、7天的相关系数r分别为0.83、0.89、0.83,P=0.000;舒张压降低幅度和血肿周围水肿体积之间有相关性,在第3、5、7天的相关系数r分别为0.82、0.89、0.84,P=0.000)。(2)降压组血肿周围水肿的AQP4表达下调均优于未干预组,强化降压组优于常规降压组,差异有统计学意义,第3、5、7天的F值分别为217.058、21、51.706(P<0.05)。结论 (1)氨氯地平有效降压能使脑出血血肿周围水肿缩小;(2)氨氯地平可能通过抑制AQP4表达促使血肿周围脑水肿减轻;(3)收缩压、舒张压的升高均可促使血肿周围脑水肿扩大。

Objective To explore the correlation between the potential mechanism of edema around the hematoma and antihypertensive therapy in spontaneously hypertensive rats（SHRs）.Methods A model of intracerebral hemorrhage was induced by infusion of bacterial collagenase into the SHRs brains.The rats were randomly assigned to intracerebral hemorrhage group,amlodipine treatment group and intensive amlodipine treatment group.The rats were decapitated and brain tissues were collected.The histological morphlogical change was investigated.Cerebral edema formation was determined by brain water content using MRI methods.The expression of AQP4 in brain tissue was observed by immunohistochemical assay and Real-time PCR.Results In amlodipine treatment group,MRI detected that cerebral hematoma and edema in the CCB group and the ICCB group were better than no intervention group,and the ICCB group was superior than the CCB group,the difference was statistically significant（F=16.987,35.448,37.174 P0.05）.Systolic blood pressure reduction ranges and reduction of the rate of edema around the hematoma had correlation（r=0.83,0.89,0.83,P=0.000））.Diastolic blood pressure reduction ranges and reduction the rate of edema around the hematoma had a correlation（r=0.82,0.89,0.84,P=0.000）.AQP4 expression around hematoma of the CCB group and the ICCB group was better than the untreated group on 1d,3d,5d and 7d,and the ICCB group was superior to the CCB group,the difference was statistically significant（F=217.058,21.000,51.706,P0.05）.Conclusion Amlodipine can decrease intracerebral hemorrhage surrounding edema.Amlodipine improves edema through inhibiting AQP4 expression.The increase of systolic blood pressure or diastolic blood pressure can promote the hematoma and surrounding edema to expand.