阿托伐他汀对自发性高血压大鼠心室重构的影响

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (8): 880-884.

阿托伐他汀对自发性高血压大鼠心室重构的影响

王安才, 成蓓, 谢晓竟¹, 徐浩¹

华中科技大学同济医学院协和医院心内科, 武汉430022, 湖北;
¹皖南医学院弋矶山医院心内科, 芜湖241001, 安徽

收稿日期:2004-06-19 修回日期:2004-07-15 出版日期:2004-08-26 发布日期:2020-11-20
通讯作者: 成蓓,女,主任医师,教授,博士生导师,研究方向:老年心血管病临床。Tel:027-85726005 E-mail:chengbei@public.wh.hb.cn
作者简介:王安才,男,主任医师,博士,教授,硕士生导师,研究方向:心血管病临床。Tel:0553-5739313 E-mail:yjswac@sina.com

Effects of atorvastatin on ventricular remodeling in spontaneously hypertensive rats

WANG An-Cai, CHENG Bei, XIE Xiao-Jing¹, XU Hao¹

Department of Cardiology, Xiehe Hospital, Tongji Medical College, Huazhong Science &Technology University, Wuhan 430022, Hubei, China;
¹Department of Cardiology, Yijishan Hospital, Wannan Medical College, Wuhu 241001, Anhui, China

Received:2004-06-19 Revised:2004-07-15 Online:2004-08-26 Published:2020-11-20

摘要/Abstract

摘要： 目的: 观察阿托伐他汀对自发性高血压大鼠(SHR)心室重构的影响。方法: 24只SHR 随机分为4组,每组6只。SHR对照组、阿托伐他汀50mg组(50mg·kg^-1·d^-1)、阿托伐他汀10mg组(10 mg·kg^-1·d^-1)和缬沙坦组(20mg·kg^-1·d^-1);6只Wistar-Kyoto 大鼠(WKY)作为正常对照组。灌胃给药共6 周,分别于给药前和给药后每2 周测量大鼠尾动脉收缩压(SBP)。酶法测定血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)含量,放免法测定血浆和心肌血管紧张素Ⅱ(Ang Ⅱ)水平,并检测心肌羟脯氨酸、胶原蛋白含量和全心重量(HW)、左室重量(LVM)及左室重量指数(LVMI)。透射电镜观察心肌超微结构改变。结果: 用药前SHR 各组SBP均显著高于WKY 正常对照组(P<0.01),给药后第4、6 周,阿托伐他汀50 mg 组SBP明显下降(P<0.01),阿托伐他汀10 mg 组不明显;缬沙坦组自给药后第2 周,SBP明显下降(P<0.01)。阿托伐他汀50 mg 组TC、TG 及LDL-C水平较SHR 对照组明显降低(P<0.05或P<0.01),阿托伐他汀10 mg 组仅LDL-C 水平明显下降(P<0.05)。SHR对照组血浆Ang Ⅱ浓度与WKY 正常对照组比较无显著性差异,但心肌Ang Ⅱ浓度明显增高(P<0.05);给药6 周后,阿托伐他汀各剂量组和缬沙坦组血浆Ang Ⅱ浓度显著高于SHR 对照组(P<0.01),而心肌Ang Ⅱ 浓度在阿托伐他汀50 mg 组和缬沙坦组明显降低(P<0.05)。SHR 对照组心肌羟脯氨酸和胶原蛋白含量较WKY 正常对照组明显升高(P<0.01);6 周后,阿托伐他汀50 mg 组较SHR 对照组降低(P<0.05)。SHR组HW、LVM和LVMI与WKY正常对照组相比增高(P<0.01),而阿托伐他汀50 mg 组却低于SHR 对照组(P<0.05)。透射电镜观察心肌超微结构显示,阿托伐他汀50mg组和缬沙坦组与SHR对照组比较,心肌细胞核膜较完整,肌原纤维清晰,排列较整齐,横纹清楚,间质胶原纤维无明显增生。结论: 阿托伐他汀能明显改善SHR 的心室重构,降低血压和心肌Ang Ⅱ浓度可能为其机制之一。

关键词: 阿托伐他汀, 自发性高血压大鼠, 高血压, 心室重构, 血管紧张素Ⅱ, 羟脯氨酸

Abstract: AIM: To investigate the effects of atorvastatin on ventricular remodeling in spontaneously hypertensive rats (SHR).METHODS: SHRs (n=24)were randomly divided into four groups (n=6):SHR control group, 50 mg atorvastatin group (50 mg·kg^-1·d^-1), 10mg atorvastatin group (10 mg·kg^-1 ·d^-1)and valsartan group (20 mg·kg^-1 ·d^-1).Six male Wistar-Kyoto rats were selected as normal control group (WKY group). Systolic blood pressure (SBP)was measured before and after treatment with atorvastatin every 2 weeks.Plasma concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C)and Ang ,and myocardial Ang Ⅱ, hydroxyproline and collagen levels were measured.Heart weight (HW), left ventricle mass (LVM)and left ventricle mass index (LVMI)were gauged.Myocardial ultrastructure was observed by transmission electron microscopy.RESULTS: SBP in all SHR groups was much higher than that in WKY group beforeexperiment (P<0.01).SBP significantly decreased in 50 mg atorvastatin group at 4 weeks and 6 weeks (P< 0.01).Compared with SHR control group, there was a significant descent in serum TC, TG and LDL-C concentrations in 50 mg atorvastatin group (P<0.05, or P <0.01).The level of LDL-C decreased merely in 10 mg atorvastatin group (P<0.05).There was no difference in plasma Ang Ⅱ level among WKY group and SHR groups.But myocardial Ang Ⅱ level in SHR group was significantly higher than that inWKY group (P<0.05). After 6 weeks, plasma Ang Ⅱ level among atorvastatin groups and valsartan group was markedly higher than that in SHR control group (P<0.01), and myocardial Ang Ⅱ level was significantly lower than that in SHR group (P<0.05).Myocardial hydroxyproline and collagen level in SHR group was significantly higher than that in WKY group (P<0.01).After treatment of 50 mg atorvastatin, it was markedly lower than that in SHR control group (P<0.05).Compared with WKY group, HW, LVM and LVMI were significantly increased in SHR group (P<0.01).After treatment of 50 mg atorvastatin, HW, LVM and LVMI were significantly lower than those in SHR control group (P<0.05).The changes of myocardial ultrastructure in atorvastatin and valsartan groups were significantly improved.CONCLUSION: Atorvastatin can significantly improve ventricular remodeling in SHR, and decrease blood pressure and myocardial Ang Ⅱ level which may be one of its mechanisms.

Key words: atorvastatin, spontaneously hypertensive rats, hypertension, ventricular remodeling, angiotensin Ⅱ, hydroxyproline

中图分类号:

R965
R972.4

王安才, 成蓓, 谢晓竟, 徐浩. 阿托伐他汀对自发性高血压大鼠心室重构的影响[J]. 中国临床药理学与治疗学, 2004, 9(8): 880-884.

WANG An-Cai, CHENG Bei, XIE Xiao-Jing, XU Hao. Effects of atorvastatin on ventricular remodeling in spontaneously hypertensive rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(8): 880-884.

参考文献

1 O’Driscoll G, Green D, Taylor RR.Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 months[J].Circulation, 1997;95(5):1126-31
2 Osamah H, Mira R, Sorina S, Shlomo K, Michael A.Reduced platelet aggregation after fluvastatin therapy is associated with altered platelet lipid composition and drug binding to the platelets[J].Br J Clin Pharmacol, 1997;44(1):77-83
3 Ridker PM, Rifai N, Marc A, Pfeffer MA, Sacks F, Braunwald E.Long-term effects of pravastatin on plasma concentration of C-reactive protein. The cholesterol and recurrent events (CARE)investigators[J].Circulation, 1999;100(3):230-5
4 Guijarro C, Blanco-Colio LM, Ortego M, Alonso C, Ortiz A, Plaza JJ, et al.3-hydroxy-3-methylglutaryl coenzyme A reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture[J].Circ Res, 1998;83(5):490-500
5 Wassmann S, Laufs U, Bä umer AT, Mǜller K, Ahlbory K, Linz W, et al.HMG-CoA reductase inhibitors improve endothelial dysfunction in normocholesterolemic hypertension via reduced production of reactive oxygen species[J].Hypertension, 2001;37(6):1450-7
6 Wong B, Lumma WC, Smith AM, Sisko JT, Wright SD, Cai TQ.Statins suppress THP-1 cell migration and secretion of matrix metalloproteinase 9 by inhibiting geranylgeranyllation 3[J].J Leukoc Biol, 2001;69(6):959-62
7 Su SF, Hsiao CL, Chu CW, Lee BC, Lee TM.Effects of pravastatin on left ventricular mass in patients with hyperlipidemia and essential hypertension[J].Am J Cardiol, 2000;86(5):514-8
8 Patel R, Nagueh SF, Tsybouleva N, Abdellatif M, Lutucuta S, Kopelen HA, et al.Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy[J].Circulation, 2001;104(3):317-24
9 吴扬, 潘敬运.血管紧张素Ⅱ 对培养新生大鼠心肌病MHC 基因表达的影响[J].中国病理生理杂志, 1998;14(2):126-9
10 Sadoshima JI, Izumo S.Molecular characterization of angioten-sin Ⅱ-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts[J].Circ Res, 1993;73(3):413-23
11 Sadoshima J, Xu Y, Slayter HS, Izumo S.Autocrine release of angiotensin Ⅱ mediates stretch-induced hypertrophy of cardiac myocytes in vitro[J].Cell, 1993;75(5):977-84

[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]	李青华, 赵艳, 赵海港, 高朋飞, 徐炳欣. ABCB1 G2677T 基因多态性检测在缺血性脑卒中患者应用阿托伐他汀降脂治疗中的价值[J]. 中国临床药理学与治疗学, 2023, 28(6): 633-640.
[3]	宁思思, 赵玉红, 颜蕾, 唐敏娜, 张凝之, 张泳巧, 崔兆强. 高血压合并慢性肾脏病患者的降压目标之争议[J]. 中国临床药理学与治疗学, 2023, 28(4): 463-467.
[4]	付虹, 田磊. 缺血性脑卒中伴高血压病患者个体化精准治疗的研究[J]. 中国临床药理学与治疗学, 2022, 27(8): 870-876.
[5]	陈文刚, 殷勤, 张巍巍, 周露露, 寇婉青, 袁小龙. 皖南地区高血压患者MTHFR基因多态性分布及与血Hcy相关性研究[J]. 中国临床药理学与治疗学, 2022, 27(7): 768-774.
[6]	梁美芳, 陈庆状, 杨沛群, 王勇. 基于真实世界的阿托伐他汀仿制药和原研药防治缺血性脑卒中/短暂性脑缺血发作的有效性和安全性比较[J]. 中国临床药理学与治疗学, 2022, 27(7): 785-792.
[7]	张凝之, 赵玉红, 唐敏娜, 张泳巧, 宁思思, 崔兆强. 时辰药理学在高血压治疗中的应用[J]. 中国临床药理学与治疗学, 2022, 27(4): 418-422.
[8]	崔素梅, 崔兆强. β受体阻滞剂与高血压治疗[J]. 中国临床药理学与治疗学, 2022, 27(4): 423-427.
[9]	李远方, 崔兆强. 高血压合并高尿酸血症的应对之策[J]. 中国临床药理学与治疗学, 2022, 27(4): 428-432.
[10]	徐建飞, 林利. 高血压药物治疗与非药物治疗研究进展[J]. 中国临床药理学与治疗学, 2022, 27(4): 433-441.
[11]	蒯铮, 张潇伊, 邹云增. 血管紧张素受体脑啡肽酶抑制剂在老年高血压中的应用[J]. 中国临床药理学与治疗学, 2022, 27(4): 442-445.
[12]	刘桂剑, 程宽, 朱文青, 葛均波. 高血压的药物治疗进展[J]. 中国临床药理学与治疗学, 2022, 27(4): 446-449.
[13]	邢开, 龚金玉, 罗建权. 噻嗪类利尿剂相关不良反应的药物基因组学研究进展[J]. 中国临床药理学与治疗学, 2021, 26(2): 204-212.
[14]	叶鹏, 谭兴, 冷岳奇, 王杨凯, 王伟忠. 基于交感神经系统的高血压非药物治疗研究现状和进展[J]. 中国临床药理学与治疗学, 2021, 26(12): 1335-1343.
[15]	赵玮, 吴悠扬, 林丛, 黄时伟, 陈皓, 姜文兵. 紫檀芪对急性心肌梗死大鼠心肌功能、心肌纤维化和炎症反应的作用及对Notch1/eIF3a信号通路的影响[J]. 中国临床药理学与治疗学, 2020, 25(5): 498-504.