易卒中型肾血管性高血压大鼠脑组织及血清中基质金属蛋白酶9的表达

Expressions of matrix metalloproteinase-9 in brain and serum in stroke-prone renovascular hypertensive rats

目的探讨易卒中型肾血管性高血压大鼠(RHRSP)脑组织及血清中基质金属蛋白酶9(MMP-9)的表达及在高血压脑卒中发生中的作用。方法健康雄性SD大鼠50只随机分成RHRSP组(35只)和假手术组(15只)。RHRSP组采用双肾双夹法造模,鼠尾测压仪测定收缩压。根据Longa5评分法和病理学结果再将RHRSP组分为脑卒中组和非脑卒中组。免疫组化测定脑组织中MMP-9的表达,双抗体夹心ELISA检测血清MMP-9水平。结果与假手术组比较,RHRSP组术后4、8、12周血压均升高[(165±10)比(109±8),(194±11)比(112±9),(248±38)比(113±9)mmHg,均P<0·05];RHRSP组中有11只大鼠发生脑卒中,卒中率34·4%。脑卒中和非脑卒中大鼠的血压无明显差异(P>0·05)。术后8周和12周,与非脑卒中大鼠比较,脑卒中大鼠血清MMP-9均升高[(7·15±2·46)比(5·53±1·59),(9·47±3·23)比(6·85±1·08)μg/L,均P<0·05];非脑卒中大鼠血清MMP-9明显高于假手术组(P<0·05)。术后12周,脑卒中大鼠脑组织MMP-9的表达明显高于非脑卒中大鼠和假手术组大鼠(均P<0·05)。Pearson相关分析显示,RHRSP组术后12周血压与血清及脑组织中的MMP-9均呈正相关(r=0·436和r=0·612,P<0·05)。结论持续的高血压能使MMP-9表达升高,可能与高血压大鼠脑血管壁的病理损害甚至脑卒中的发生有关。

Objective To investigate the expressions of brain and serum matrix metalloproteinase-9（MMP-9） in stroke-prone renovascular hypertensive rats （RHRSP）, and the effect of its expressions on the pathogenesis of hypertensive stroke. Methods Fifty healthy male SD rats were randomly divided into RHRSP group（n=35）and sham-operated group （n=15）. Renovascular hypertension models were established by two-kidney, two-clip （2K2C） method in RHRSP group. Systolic blood pressure （SBP） was measured by a tail pressure meter. Assessed by Longa＇s five-point scale and pathologic examination, RHRSPs were divided into stroke group and non-stroke group. The MMP-9 expressions in brain tissues were detected by immunohistochemical method and the levels of serum MMP-9 were measured by double-antibody sandwich enzyme-linked immunosorbent assay（DAS-ELISA）. Results Compared with that in sham-operated group, SBP stayed significantly elevated in RHRSP group 4, 8 and 12 weeks after the operation[（165±10） vs （109±8）, （194±11） vs （112±9）,（248±38）vs （113±9）mm Hg, all P0.05]. Stroke occurred in 11 rats （34.4%） in RHRSP group. There was no significant difference in blood pressure between stroke group and non-stroke group（P0.05）. Eight and 12 weeks after the surgery, the level of serum MMP-9 in stroke group kept significantly higher than that in non-stroke group [（7.15±2.46）vs （5.53±1.59）, （9.47±3.23） vs （6.85±1.08） μg/L, all P0.05] and and the level was markedly higher in non-stroke group than that in sham-operated group （P0.05）. The expression of MMP-9 expression in brain tissues in stroke group was distinctly higher than that in non-stroke group and sham-operated group （both P0.05） 12 weeks after the surgery. Pearson correlation analysis showed that MMP-9 levels in serum and brain in RHRSP group were positively correlated with blood pressure 12 weeks after the surgery （r=0.436 and r=0.612, P0.05）. Conclusion Prolonged hypertension could induce increased expression of MMP-9, which is probably related to the pathological lesion of cerebral vessel walls and even pathogenesis of stroke in hypertension rats.