氨氯地平联合ALT-711对自发性高血压大鼠大动脉硬化的干预作用

Intervention of Amlodipine Combined with ALT-711 on Arteriosclerosis of Spontaneously Hypertensive Rats

目的:观察氨氯地平联合晚期糖基化终末产物交联蛋白裂解剂(ALT-711)对高血压治疗作用以及探索防治高血压大动脉硬化的优化方案。方法:选用10周龄的雄性自发性高血压大鼠(SHR)18只,随机分为3组每组6只:SHR对照组(A组):生理盐水1 ml/(kg.d)灌胃;氨氯地平治疗组(B组):1 mg/(kg.d)氨氯地平灌胃。ALT-711+氨氯地平干预组(C组):10 mg/(kg.d)ALT-711+1 mg/(kg.d)氨氯地平灌胃。共给药8周。8周后麻醉处死动物,取大动脉切片Masson染色,图像分析测定胶原容积分数,免疫组化法检测三组SHR大鼠大动脉晚期糖基化终末产物(AGEs)、整合素β1和纤维连接蛋白(FN)的表达率。结果:与对照组比较,治疗组B组和C组SHR大鼠的血压显著降低,且AGEs、整合素β1和FN的阳性表达率降低差异有统计学意义(P<0.05)。结论:ALT-711联合氨氯地平能促进SHR主动脉细胞外基质的降解,提示ALT-711联合氨氯地平治疗SHRs在降压治疗同时防治大动脉硬化方面较单用氨氯地平更优。

Objective： To investigate the intervention of amlodipine combined with ALT-711 on blood pressure and arteriosclerosis of Spontaneously Hypertensive Rats （SHRs）. Methods. Eighteen ten-week-old male SHRs were randomly and equally divided into three groups as untreated SHR group （group A）, amlodipine treated SHR group （group B）, and amlodipine plus ALT-711 treated group （group C）. After eight weeks, all SHRs were executed after anesthesia. Rat＇s aortas were sliced, and the collagen volume fraction was measured by Masson staining and image analysis. The expression of advanced glycation end-products （AGEs）, integrin 131, and fibronectin （FN） in aorta were measured by immunohistochemistry staining. Results： Compared with that in group A, the blood pressure of group B and group C significantly decreased respectively. Positive expression of AGEs, intergrin β1, and FN in C group were significantly decreased as compared with those in group A and group B respectively （all P〈0.05）. Conclusion： ALT-711 plus amlo-dipine is better than amlodipine solo treatment in enhancing the extracellular matrix degradation of SHRs aortas, although both methods have no significant difference in decreasing blood pres- sure in SHRs.