罗格列酮逆转心力衰竭大鼠心脏间质纤维化的实验研究

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (8): 896-899.

罗格列酮逆转心力衰竭大鼠心脏间质纤维化的实验研究

刘洪智^1,2, 高传玉¹, 雷健³, 罗兵³, 李佐民³, 周军³, 贺立群³, 戚本玲², 曹林生²

¹河南省人民医院心内科, 郑州 450000, 河南;
²华中科技大学同济医学院附属协和医院心内科, 武汉 430022, 湖北;
³武汉市第一医院心内科, 武汉 430022, 湖北

收稿日期:2007-01-22 修回日期:2007-08-30 出版日期:2007-08-26 发布日期:2020-10-27
作者简介:刘洪智,男,博士,主治医师,研究方向:心力衰竭及冠心病诊治。Tel:0371-65580756 E-mail:lhzhi@sina.com
基金资助:
武汉市科技计划项目(200302)

Experimental study on rosiglitazone reversing myocardial interstitial fibrosis of rats with heart failure

LIU Hong-zhi^1,2, GAO Chuan-yu¹, LEI Jian³, LUO Bing³, LI Zuo-min³, ZHOU Jun³,HE Li-qun³, QI Ben-ling², CAO Lin-sheng²

¹Department of Cardiology, Henan Province Peoples Hospital, Zhengzhou 45000, Henan, China;
²Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China;
³Department of Cardiology, Wuhan First Hospital, Wuhan 430022, Hubei, China

Received:2007-01-22 Revised:2007-08-30 Online:2007-08-26 Published:2020-10-27

摘要/Abstract

摘要： 目的: 研究过氧化酶体增殖物激活受体γ(PPARγ)配体罗格列酮能否逆转心力衰竭大鼠心脏间质纤维化。方法: 60 只雄性Wistar 大鼠分3 组:(1)心力衰竭模型组(CHF, n=25), 阿霉素2.5 mg/kg, 尾静脉注射, 每周1 次, 连续10 周;(2)心力衰竭模型+罗格列酮治疗组(ROS, n=25), ROS3 mg·kg^-1·d^-1, 灌胃治疗;(3)正常对照组(CON, n=10)。于实验第12 周, 进行超声检测评价其心功能, 用放免法检测血浆TNF-α、血管紧张素-II(Ang-Ⅱ)及醛固酮(Ald)水平, 氯胺T 法检测羟脯氨酸及胶原含量, 苦味酸天狼星红染色进行左室胶原特异染色及定量分析, 计算胶原容积分数(CVF), 并作HE 染色观察其组织学变化。结果: ROS 组较CHF组死亡率明显降低(20% vs 40%, P<0.01)。与CON 组相比,CHF 组血浆TNF-α、Ang-Ⅱ 及Ald 水平升高(P<0.01), 而ROS 治疗组较CHF 组降低(P<0.01)。CHF 组羟脯氨酸及胶原含量增加(P<0.01), 经ROS 治疗后有所减低。苦味酸天狼星红染色显示CHF 组左室胶原明显增加,CVF 明显增高(P<0.01);而ROS 组则纤维化明显减轻,CVF 降低(P<0.01)。病理学结果证实CHF 组符合心肌病样改变, 而ROS 组可逆转这种改变。结论: PPARγ配体罗格列酮通过抑制TNF-α、Ang-Ⅱ及Ald 等, 部分逆转心力衰竭大鼠心脏间质纤维化。

关键词: 过氧化酶体增殖物激活受体γ, 罗格列酮, 阿霉素, 心力衰竭, 间质纤维化

Abstract: AIM: To investigate whether the ligand of peroxisome Proliferator-activated receptor γ(PPARγ), rosiglitazone (ROS), can reverse myocardial interstitial fibrosis in rats with heart failure. METHODS: Sixty weight-matched adult male Wistar rats were randomly divided into 3 groups as follows:(1)the CHF group, in which 2.5 mg/kg of adriamycin (ADR)was weekly injected via a tail vein for 10 weeks (n=25);(2)the ROS group, concomitant ROS and ADR, in which ROS as a PPARγligand was administered by daily gavage at a dose of 3 mg·kg^-1·d^-1(n=25);(3)the control group (n=10).The cardiac function was evaluated by echocardiographic method.The plasma concentrations of TNF-α, Angiotensin II (Ang II)and Aldsterone (Ald)were determined by immunoradiometric assay at 12 weeks after treatment.The hydroxyproline and collagen content were determined by the methods of Chloramines T and Picric acid-Sirius red staining techniques.The pathological change was analyzed by histological hematoxylin-eosin staining. RESULTS: The mortality of ROS-treated rats was significantly lower than that of CHF group (20% versus 40%, P<0.01).The plasma concentrations of TNF-α, Ang II and Ald were higher in the CHF group than those in the control group (P<0.01), which was decreased by ROS treatment.The hydroxyproline and collagen content were increased in CHF group(both P<0.01), but decreased in ROS group.The myocardial collagen of left ventricle increased and the collagen volume fraction (CVF)increased significantly, which were partly reversed by ROS treatment(P<0.01).The pathological results showed there was changes of cardiomyopathy in CHF group, ROS reversed the pathological changes of left ventricular myocardium of CHF. CONCLUSION: Pretreatment with PPARγligand ROS could partly reverse myocardial interstitial fibrosis in rats with heart failure by downregulating the expression of TNF-α, Ang II and Ald.

Key words: peroxisome proliferator activated receptor γ, rosiglitazone, adriamycin, heart failure, interstitial fibrosis

中图分类号:

R965.2

刘洪智, 高传玉, 雷健, 罗兵, 李佐民, 周军, 贺立群, 戚本玲, 曹林生. 罗格列酮逆转心力衰竭大鼠心脏间质纤维化的实验研究[J]. 中国临床药理学与治疗学, 2007, 12(8): 896-899.

LIU Hong-zhi, GAO Chuan-yu, LEI Jian, LUO Bing, LI Zuo-min, ZHOU Jun,HE Li-qun, QI Ben-ling, CAO Lin-sheng. Experimental study on rosiglitazone reversing myocardial interstitial fibrosis of rats with heart failure[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(8): 896-899.

[1]	郝潇, 赵美, 王文静, 张飞飞, 刘惠良, 党懿, 李树仁, 齐晓勇. 钠-葡萄糖共转运体2抑制剂在急性心肌梗死应用研究进展[J]. 中国临床药理学与治疗学, 2023, 28(7): 824-831.
[2]	马月, 马旺博, 周智华, 常静雯, 范方田. 槲皮素干预肾间质成纤维细胞糖酵解抗肾间质纤维化机制研究[J]. 中国临床药理学与治疗学, 2023, 28(2): 121-129.
[3]	彭勇, 范剑峰, 熊旭华, 肖冬平, 高招波, 郑春华. 右旋糖酐铁片对合并铁缺乏的射血分数减低的心力衰竭患者的影响[J]. 中国临床药理学与治疗学, 2023, 28(2): 178-183.
[4]	陈玉林, 蒋虎刚, 王新强, 刘凯, 李应东, 安涛, 赵信科. 基于网络药理学和分子对接探讨芪参益心颗粒治疗射血分数保留型心力衰竭的作用机制[J]. 中国临床药理学与治疗学, 2023, 28(10): 1081-1092.
[5]	杨胜, 王德国. 沙库巴曲缬沙坦联合达格列净治疗射血分数减低型心力衰竭疗效及对血清cTnⅠ、BNP水平的影响[J]. 中国临床药理学与治疗学, 2022, 27(9): 1010-1015.
[6]	武利军, 李馨, 崔丽娟, 李欣欣, 王燕. 基于蛋白质组学分析奈比洛尔改善UUO大鼠肾间质纤维化[J]. 中国临床药理学与治疗学, 2022, 27(7): 729-738.
[7]	孙莹, 余勤. 凝血纤溶系统失衡与特发性肺间质纤维化发病机制及治疗的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(6): 689-695.
[8]	彭娟, 范琳琳, 李然宜, 李晓宇, 吕迁洲, 邹云增. 心力衰竭药物治疗的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(4): 373-381.
[9]	刘平, 邱博, 吴惠珍. 维利西呱治疗心力衰竭的药理作用与临床评价[J]. 中国临床药理学与治疗学, 2022, 27(2): 212-218.
[10]	徐永华, 施向红. 托拉塞米联合左卡尼汀治疗慢性心力衰竭的疗效分析[J]. 中国临床药理学与治疗学, 2021, 26(6): 647-652.
[11]	丁雪明, 陈天鹏, 徐强, 何欢, 何明. 川芎嗪通过14-3-3γ/Bcl-2减轻阿霉素引起的心肌毒性[J]. 中国临床药理学与治疗学, 2021, 26(4): 361-367.
[12]	金乐, 蒋多晨, 陈洪晓, 刘苏, 陈昭琳, 居靖. 槲皮素通过GAS5调控GSK-3β/β-catenin逆转乳腺癌阿霉素耐药[J]. 中国临床药理学与治疗学, 2021, 26(12): 1344-1351.
[13]	陈力方, 王博, 王维蓉. 组蛋白去乙酰化酶3在心血管疾病中的研究进展[J]. 中国临床药理学与治疗学, 2021, 26(1): 88-97.
[14]	潘战和, 王馨, 苏安, 张鹏, 纪浩南, 王小梅. 基于Notch 1/NF-κB/STAT3通路探讨塞来昔布逆转NK/T细胞淋巴瘤细胞阿霉素耐药的作用机制[J]. 中国临床药理学与治疗学, 2020, 25(12): 1330-1336.
[15]	范剑峰，方译，郑春华. 沙库巴曲缬沙坦钠治疗慢性心力衰竭患者的临床疗效分析[J]. 中国临床药理学与治疗学, 2019, 24(7): 810-814.