MMP-9与TGF-β_1在高血压血管重构中的作用及阿托伐他汀的干预研究

Hypertensive vascular remodeling:the roles of matrix metalloproteinase-9 and transforming growth factor-β1 and outcomes of atorvastatin intervention

目的探讨基质金属蛋白酶-9(MMP-9)和转化生长因子-β1(TGF-β1)在高血压血管重构中的作用及阿托伐他汀的干预研究。方法采用两肾一夹方法建立肾性高血压大鼠模型,将24只大鼠随机分为对照组(8只),高血压组(8只),阿托伐他汀组(8只),术后4周末开始用阿托伐他汀(50mg·kg-1·d-1)连续灌胃8周。检测大鼠尾动脉收缩压(SBP),光镜下观察血管结构变化并计算胸主动脉中层壁厚与内径之比(M/L),免疫组织化学法检测MMP-9与TGF-β1的表达水平。结果高血压组较对照组SBP、M/L显著升高,MMP-9的表达水平显著增强,而TGF-β1表达水平显著降低(P均<0.01)。阿托伐他汀组较高血压组M/L明显降低,MMP-9的表达水平明显降低,而TGF-β1表达水平明显升高(P均<0.05)。结论MMP-9可能与高血压血管重构的形成有关,TGF-β1可能是高血压血管重构中的保护性因子,阿托伐他汀可以抑制大鼠血管重构的形成,其机制可能与抑制MMP-9、增强TGF-β1的表达有关。

Objective To investigate the roles of matrix metalloproteinase（MMP）-9 and transforming growth factor-β1 （TGF-β1） in hypertensive vascular remodeling and outcomes of atorvastatin intervention in this condition. Methods Renal hypertension rat models were constructed through the two-kidney-one-clip technique. Twenty-four rats were randomized into the control group （n=8）, hypertension group （n=8） or atorvastatin-treated group （n=8）. Atorvastatin treatment （50 mg·kg^-1·d^-1） was started four weeks after model construction and lasted 8 consecutive weeks, given through galvage. All rats were evaluated for caudal systolic blood pressure （SBP）, microscopic changes in vascular structure and ratio of intima media thickness to lumen diameter （M/L） of thoracic aorta. Expressions of MMP-9 and TGF-β, were assessed with immunohistochemical staining. Results Compared with the control group, the hypertension group showed significantly increased SBP and M/L, enhanced MMP-9 expression and lowered level of TGF-β, （all P〈 0.01）. Atorvastatin group showed significantly lowered M/L and MMP-9 expression but remarkably increased TGF-β, expression as compared with hypertension group （all P〈0.01）. Conclusion MMP-9 may be related to development of hypertensive vascular remodeling in which TGF-β, may be a protective factor. Atorvastatin was shown to inhibit the development of vascular remodeling in rats, possibly associated with decreased expression of MMP-9 and enhanced expression of TGF-β