MiR-26a/b在AngⅡ导致的高血压血管重塑中的作用
Role of miR-26a/b in AngⅡ-induced hypertensive vascular remodeling

摘要：目的 检测小鼠主动脉和血清中miR-26a/b的表达水平的变化，探讨miR-26a/b在高血压血管重塑中的作用。方法 将C576L/BJ雄性小鼠随机分为AngⅡ组和对照组。在小鼠背部皮下植入微渗透泵，持续泵入AngⅡ[2.0mg/(kg？d)]建立小鼠高血压血管重塑模型。对照组泵入生理盐水。分别于干预前和干预后的第3、5、7、10、14天进行血压测定。2周后处死小鼠，留取血清及主动脉组织，用RT-PCR测定miR-26a/b的表达水平。HE、Masson染色以及免疫组化观察血管形态学的变化、纤维化程度以及蛋白表达情况。结果 干预后，AngⅡ组的收缩压明显高于对照组(P<0.05)，AngⅡ组的舒张压也明显高于对照组(P<0.05)；主动脉HE染色显示AngⅡ组血管管壁较对照组明显增厚；Masson三色染色显示AngⅡ组主动脉中层有较多蓝色的胶原纤维沉积，对照组主动脉中层未见明显的胶原纤维沉积；RT-PCR显示AngⅡ组小鼠外周血血清和主动脉中miRNA-26a/b的表达量低于对照组(P<0.05)；免疫组化显示泵入AngⅡ后，CTGF、collagenⅠ、collagenⅢ的表达水平升高(P<0.05)。结论 miR-26a/b、CTGF、collagenⅠ、collagenⅢ 都可能参与AngⅡ引起的高血压血管重塑，miR-26a/b在一定程度上可能成为高血压血管重塑的新的治疗靶点。
ABSTRACT: Objective To detect the expression of miR-26a/b in the aorta and serum of mice so as to explore the role of miR-26a/b in vascular remodeling of hypertension. Methods C576L/BJ male mice were randomly divided into AngⅡ group and control group. Mini-osmotic pump was implanted subcutaneously into the back of mice, and the model of blood vessel remodeling in mice was established by continuous infusion of AngⅡ(2.0mg/kg？d). The mice in control group were injected with saline. Blood pressure was taken before the intervention and at 3, 5, 7, 10 and 14 days after the intervention. After 2 weeks, the mice were killed, the serum and aorta tissues were collected, and the expression of miR-26a/b was determined by RT-PCR. HE staining, Masson staining and immunohistochemistry were performed to observe changes in vascular morphology, fibrosis and protein expression. Results After the intervention, systolic blood pressure and diastolic blood pressure were significantly higher in AngⅡ group than in control group (P<0.05). HE staining showed that the vessel wall of AngⅡ group was thicker than that of control group. Masson staining showed more blue collagen deposition in the middle of aorta in AngⅡ group but no obvious collagen deposition in control group. RT-PCR showed that the expression of miRNA-26a/b in the serum and aorta of AngⅡ group was significantly lower than in control group (P<0.05). Immunohistochemistry indicated that the expressions of CTGF, collagen Ⅰ and collagen Ⅲ all increased after AngⅡ infusion (P<0.05). Conclusion MiR-26a/b, CTGF, collagen Ⅰ and collagen Ⅲ may be involved in AngⅡ-induced vascular remodeling in hypertension. MiR-26a/b may be a new therapeutic target of vascular remodeling in hypertension