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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 observe the therapeutic effect of amlodipine combined with advanced glycation end products (ALT-711) on hypertension and to explore the optimal solution to prevent and treat hypertensive arteriosclerosis. Methods: Eighteen male 10-week-old spontaneously hypertensive rats (SHR) were randomly divided into three groups with 6 rats in each group: SHR control group (A): saline 1 ml / (kg.d) ; Amlodipine treatment group (B group): 1 mg / (kg.d) amlodipine gavage. ALT-711 + amlodipine intervention group (group C): Amlodipine 10 mg / (kg.d) ALT-711 + 1 mg / (kg.d). A total of 8 weeks. After 8 weeks, animals were sacrificed by anesthesia, Masson staining was performed on the sections of the aorta, the volume fraction of collagen was measured by image analysis. The levels of advanced glycosylation end products (AGEs), the integrin β1 and fibronectin FN) expression rate. Results: Compared with the control group, the blood pressure of SHR rats in treatment group B and C were significantly decreased, and the difference of the expression of AGEs, integrin β1 and FN was statistically significant (P <0.05). CONCLUSION: ALT-711 combined with amlodipine can promote the degradation of extracellular matrix of SHR aorta, suggesting that ALT-711 combined with amlodipine is superior to amlodipine alone in the treatment of hypertension and antihypertensive treatment.