免疫蛋白酶体β5i亚基在DOCA盐敏感高血压性心肌肥厚中的作用及机制  

The Role of Immunoproteasome β5i Subunit in DOCA Salt-induced Cardiac Hypertrophy and the Underlying Mechanism in Mice

作　　者：刘立新[1,2] 鄢雯[1,2] 李囡[2] 田翠[1] 王红霞[1] 李汇华[1] 

机构地区：[1]首都医科大学基础医学院病理学系,生理学与病理生理学系,北京市100069 [2]首都医科大学燕京医学院,北京市101300

出　　处：《中国分子心脏病学杂志》2015年第5期1469-1471,共3页Molecular Cardiology of China

基　　金：国家自然科学基金重点项目(81330003)

摘　　要：目的探讨免疫蛋白酶体β5i亚基对醋酸脱氧皮质酮(DOCA)盐敏感型高血压小鼠心肌肥厚的影响及机制。方法给野生小鼠皮下植入DOCA药片及饮用Na Cl溶液(10 g/L)三周建立高血压性心肌肥厚模型。手术前一天开始皮下注射β5i抑制剂PR-957(浓度12 mg/kg,每周4次)。三周后进行心脏超声、心肌细胞表面积、心脏组织中β5i及钙调神经磷酸酶蛋白水平的检测。结果β5i蛋白水平、心脏功能(EF%,FS%)、心肌肥厚指标(心脏重量/体重、心室壁厚度、心肌细胞面积)及钙调神经磷酸酶蛋白水平比假手术组均明显增高。相反,这些作用在PR-957处理的心脏中明显减轻。结论免疫蛋白酶体β5i亚基激活促进DOCA盐诱导的心肌肥厚,其机制部分与钙调神经磷酸酶信号通路激活相关。Objective To investigate the role of immunoproteasome β5i subunit in deoxycorticosterone acetate（DOCA） salt-induced hypertensive cardiac hypertrophy and the underlying mechanism in mice. Methods DOCA-salt hypertensive cardiac hypertrophy was induced in wild-type mice by implanting DOCA pills subcutaneously and drinking Na Cl（10 g / L） solution for 3 weeks. Immunoproteasome β5i subunit inhibitor PR-957（12 mg / kg, 4 times per week） or vehicle was administrated by subcutaneously from 1 day before the operation. Animals underwent M-mode echocardiography. Heart sections were stained with Wheat germ agglutinin（WGA） to detect cardiomyocyte surface area. Protein level was measured by Western blot analysis. Results The protein level of β5i subunit of immunoproteasome was significantly increased in the DOCA-salt-treated hearts compared with sham group. Moreover, the heart function（characterized by EF% and FS%）, the ratio of heart weight/body weight, left ventricular wall thickness, cardiomyocyte surface area as well as calcineurin protein level in the DOCA-salt-treated hearts were markedly increased compared with sham group. However, these effects were significantly attenuated in PR-957-treated hearts. Conclusions The immunoproteasome subunit β5i promotes cardiac hypertrophy in response to DOCA-salt challenge, this is partially associated with the activation of calcineurin signaling pathway.

关 键 词：免疫蛋白酶体 抑制剂PR-957 DOCA盐敏感型高血压 心肌肥厚 

分 类 号：R541.3[医药卫生—心血管疾病]