Ang1-7通过抑制内质网应激减轻高血压大鼠心肌肥厚  

Ang1-7 Improved Myocardial Hypertrophy in Hypertension Rats by Suppressing Endoplasmic Reticulum Stress

作　　者：戴亚东 丁奕瑶 马全萍 燕茹 于欣[1] 杨震 DAI Yadong;DING Yiyao;MA Quanping;YAN Ru;YU Xin;YANG Zhen(Clinical Medical College,Ningxia Medical University,Yinchuan 750004,China;Department of Cardiology,Haiyuan County People's Hospital,Haiyuan 755200,China;Laboratory of Heart Center,General Hospital of Ningxia Medical University,Yinchuan 750004,China;Heart Center,General Hospital of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学临床医学院,银川750004 [2]宁夏海原县人民医院心内科,海原755200 [3]宁夏医科大学总医院心脏中心实验室,银川750004 [4]宁夏医科大学总医院心脏中心,银川750004

出　　处：《宁夏医科大学学报》2021年第4期325-328,351,共5页Journal of Ningxia Medical University

基　　金：国家自然科学基金(81660056);宁夏教育厅高校科研项目(NGY2018-98)。

摘　　要：目的探讨血管紧张素1-7(angiotensin1-7,Ang1-7)对自发性高血压大鼠(spontaneous hypertension rat,SHR)心肌肥厚的影响及其相关机制。方法将5只16周龄Wistar-kyoto(WKY)大鼠作正常对照组(normal control,NC),10只16周龄SHR分为药物干预组(Ang1-7+SHR,AS)和安慰剂对照组(normal+SHR,NS),每组5只。AS组按400 ng·(kg·min)^(-1)的剂量皮下微渗泵连续注射Ang1-7,持续给药4周;NS组按相同容积泵速皮下微渗泵注射0.9%NaCl,持续给药4周;NC组不做任何处理。于干预结束后测量并观察血压水平变化,超声心动图检测舒张期室间隔厚度(diastolic interventricular septum,IVSd)判断心肌肥厚程度,行HE染色、Masson染色分别观察心肌细胞形态及纤维化,免疫组化检测心肌细胞葡萄糖调节蛋白78(GRP78)和C/EBP同源蛋白质(CHOP)的表达。结果干预后,与NC组比较,NS组、AS组血压均升高(P均<0.01);AS组血压较NS组降低(P<0.01)。NS组IVSd较NC组增大(P<0.05),AS组IVSd较NS组减小(P<0.05)。与NC组相比,NS组GRP78和CHOP蛋白相对表达量均增多(P均<0.05)。AS组GRP78和CHOP蛋白相对表达量均较NS组减少(P均<0.05)。同时形态学观察到AS组较NS组心肌细胞肥大程度以及纤维化均减轻。结论Ang1-7能降低SHR血压水平,减轻心肌细胞受损,缓解心肌肥厚,其作用机制可能与降低心肌细胞内质网应激相关因子GRP78、CHOP的表达水平有关。Objective To investigate the effect of Angiotensin 1-7(Ang1-7)on cardiac hypertrophy in spontaneous hypertension rat(SHR)and its related mechanism.Methods Five Wistar-kyoto(WKY)rats aged 16 weeks were used as normal control group(NC),10 rats aged 16 weeks were divided into drug intervention group(Ang1-7+SHR,AS)and placebo group(normal+SHR,NS),5 in each group.Ang1-7 was continuously injected by subcutaneous microosmotic pump at a dose of 400 ng·(kg·min)^(-1) for 4 weeks in the AS group.In NS group,0.9% NaCl was injected with subcutaneous microosmotic pump at the same volume pump rate,and the drug was administered continuously for 4 weeks.The NC group did not do any processing.After the intervention,blood pressure of 3 groups of rats was measured to observe the changes of blood pressure level.Diastolic interventricular septum(IVSd)was determined by echocardiography to determine the degree of cardiac hypertrophic.Morphology and fibrosis of myocardial cells were observed by HE staining and Masson staining.The expression of GRP78 and CHOP in myocardial cells was detected by immunohistochemistry.Results After intervention,compared with NC group,the blood pressure of NS group and AS group increased(P all<0.01).Blood pressure in AS group was significantly lower than that in NS group(P<0.01).IVSd in NS group was increased compared with NC group(P<0.05),and IVSd in AS group was significantly decreased compared with NS group(P<0.05).Compared with NC group,the relative expression levels of GRP78 and CHOP were increased in NS group(P all<0.05).The relative expression levels of GRP78 and CHOP in AS group were lower than those in NS group(P all<0.05).At the same time,morphological observation showed that cardiac hypertrophy and fibrosis were significantly reduced in AS group compared with NS group.Conclusion Ang1-7 can significantly reduce the SHR blood pressure level,reduce myocardial cell damage and alleviate myocardial hypertrophy,which is associated with the inhibition of endoplasmic reticulum stress related factors GRP78

关 键 词：血管紧张素1-7 高血压 心肌肥厚 葡萄糖调节蛋白78 C/EBP同源蛋白质 大鼠 

分 类 号：R363.1[医药卫生—病理学]