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[氯沙坦抑制大鼠主动脉血管钙化的机制]

[Mechanism of losartan suppressing vascular calcification in rat aortic artery].

作者信息

Shao Juan, Wu Panfeng, Wu Jiliang, Li Mincai

机构信息

Hubei Provincial Key Laboratory of Cardio-cerebrovascular and Metabolic Diseases, Hubei University of Science and Technology, Xianning 437100, China.

Hubei Provincial Key Laboratory of Cardio-cerebrovascular and Metabolic Diseases, Hubei University of Science and Technology, Xianning 437100, China. *Corresponding authors, E-mail:

出版信息

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2016 Aug;32(8):1060-4.

Abstract

Objective To investigate the effect of the angiotensin II receptor 1 (AT1R) blocker losartan on vascular calcification in rat aortic artery and explore the underlying mechanisms. Methods SD rats were divided randomly into control group, vascular calcification model group and treatment group. Vascular calcification models were made by subcutaneous injection of warfarin plus vitamin K1 for two weeks. Rats in the treatment group were subcutaneously injected with losartan (10 mg/kg) at the end of the first week and consecutively for one week. We observed the morphological changes by HE staining and the calcium deposition by Alizarin red staining in the artery vascular wall. The mRNA expressions of bone morphogenetic protein 2 (BMP2) and Runt-related transcription factor 2 (RUNX2) were analyzed by reverse transcription PCR. The BMP2 and RUNX2 protein expressions were determined by Western blotting. The apoptosis of smooth muscle cells (SMCs) were detected by TUNEL. The AT1R expression was tested by fluorescent immunohistochemistry. Results The aortic vascular calcification was induced by warfarin and vitamin K1. Compared with the vascular calcification model group, the mRNA and protein expressions of BMP2 and RUNX2 were significantly downregulated in the aorta in the losartan treatment group. Furthermore, the apoptosis of SMCs and the AT1R expression obviously decreased. Conclusion AT1R blocker losartan inhibits the apoptosis of SMCs and reduces AT1R expression; it downregulates the BMP2 and RUNX2 expressions in the vascular calcification process.

摘要

目的 探讨血管紧张素II受体1(AT1R)阻断剂氯沙坦对大鼠主动脉血管钙化的影响,并探究其潜在机制。方法 将SD大鼠随机分为对照组、血管钙化模型组和治疗组。通过皮下注射华法林加维生素K1两周建立血管钙化模型。治疗组大鼠在第一周结束时皮下注射氯沙坦(10mg/kg),并连续注射一周。通过HE染色观察动脉血管壁的形态学变化,通过茜素红染色观察钙沉积情况。采用逆转录PCR分析骨形态发生蛋白2(BMP2)和Runt相关转录因子2(RUNX2)的mRNA表达。通过蛋白质印迹法测定BMP2和RUNX2蛋白表达。采用TUNEL法检测平滑肌细胞(SMC)的凋亡情况。通过荧光免疫组织化学检测AT1R表达。结果 华法林和维生素K1诱导了主动脉血管钙化。与血管钙化模型组相比,氯沙坦治疗组大鼠主动脉中BMP2和RUNX2的mRNA和蛋白表达明显下调。此外,SMC的凋亡和AT1R表达明显降低。结论 AT1R阻断剂氯沙坦抑制SMC凋亡并降低AT1R表达;在血管钙化过程中下调BMP2和RUNX2表达。

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