自发性高血压大鼠颈动脉中膜基质金属蛋白酶-9和基质金属蛋白酶抑制剂-2的表达及替米沙坦的干预作用

目的:观察自发性高血压大鼠(SHR)颈动脉基质金属蛋白酶-9(MMP-9)和基质金属蛋白酶抑制剂-2(TIMP-2)的表达, 并探讨替米沙坦对其的干预作用。方法:30只雄性12周龄的SHR 随机分为3组:高血压组(SHR)、替米沙坦低剂量组(TelL)、替米沙坦高剂量组(TelH), 并设同周龄雄性的WKY 大鼠为对照组(WKY, n=10)。干预18周, 观察各组大鼠SBP 、颈动脉中膜胶原面积百分比。用免疫组化评估MMP-9和TIMP-2在颈动脉中膜的表达水平。结果:两周后TelH 组SBP 明显低于SHR 组(P<0.01), 其降压作用持续至实验结束, 而TelL 组SBP 与SHR 组无统计学差异(P>0.05)。SHR 组中膜胶原面积百分比明显高于WKY 组(P<0.01), TelH 、TelL 组的中膜胶原面积百分比低于SHR 组(P<0.05)。SHR 组中膜MMP-9的吸光度值(IOの明显低于WKY 组(P<0.01), TelH 、TelL 组中膜MMP-9的IOD 值高于SHR 组(P<0.05)。SHR 组中膜TIMP-2的IOD 值明显高于WKY 组(P<0.01), TelH 、TelL 组中膜TIMP-2的IOD 值低于SHR 组(P<0.05)。结论:SHR 颈动脉中膜MMP-9表达减少, TIMP-2表达增多, 替米沙坦能通过降压及上调MMP-9、下调TIMP-2的表达, 从而减轻颈动脉的纤维化。

Expression of MMP-9 and TIMP-2 of carotid arterial media in spontaneously hypertensive rats and the intervention study of telmisartan

AIM:To investigate the expression and the effects of telmisartan on the matrix metalloproteinase-9(MMP-9)and the tissue inhibitor of metalloproteinase-2(TIMP-2)of carotid arterial media in spontaneously hypertensive rats(SHRs).METHODS:12 week-old male SHRs were randomized to untreated SHR group (SHR), telmisartan high dose group (TelH)and telmisartan low dose group(TelL)(n=10 for each).Age and sex matched Wistar Kyoto rats (WKY)were served as control group (n=10).After 18 weeks intervention, systolic blood pressure (SBP)of rats and area of collagen fiber percentage were measured.MMP-9 and TIMP-2 expression levels in the carotid arterial media were evaluated with immunohistochemistry staining.RESULTS:After 2 weeks, the SBP level in TelH group was significantly decreased compared to SHR group (P<0.01).And the SBP lowering effect in TelH group was kept during the experiment.However, there was no significant difference between SHR group and TelL group(P>0.05).The area of collagen percentage in carotid arterial media of SHR group were higher than that in WKY group(P<0.01).In TelH and TelL group the areas were lower than that in SHR group respectively (P<0.05 for each).The integrated optical density(OD of MMP-9 in the carotid arterial media in SHR group was markedly lower than that in WKY group(P<0.01).The OD in TelH and TelL group was higher than that of SHR group respectively (P<0.05 for each).The OD of TIMP-2 in the carotid arterial media in SHR group was markedly higher than that in WKY group(P<0.01). In TelH and TelL group it was markedly lower than that of SHR group respectively(P<0.05 for each).CONCLUSION:MMP-9 expression level decreased but TIMP-2 level increased in carotid arterial media of SHRs.Telmisartan could attenuate carotid arteries fibrosis through decreasing SBP, upregulating MMP-9 and downregulating TIMP-2 expression levels on carotid arteries of SHRs.