缬沙坦降低慢性肾衰竭大鼠心肌内皮素的表达

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (6): 639-643.

缬沙坦降低慢性肾衰竭大鼠心肌内皮素的表达

徐海红, 杨利才, 杨沿浪, 张道友

皖南医学院弋矶山医院肾内科, 芜湖 241001, 安徽

收稿日期:2008-05-31 修回日期:2008-06-30 发布日期:2020-10-14
作者简介:徐海红,女,硕士研究生,副主任医师,研究方向:肾脏病基础与临床。Tel:13955355568 E-mail:ahssxhh@sohu.com
基金资助:
安徽高校省级自然科学研究项目(KJ2008B67ZC)

Valsartan decrease expression of endothelin-1 in myocardium of rats with chronic renal failure

XU Hai-hong, YANG Li-cai, YANG Yan-lang, ZHANG Dao-you

Department of Nephrology, Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui, China

Received:2008-05-31 Revised:2008-06-30 Published:2020-10-14

摘要/Abstract

摘要： 目的: 观察缬沙坦对慢性肾衰竭大鼠心肌肥厚及心肌内皮素-1(ET-1)表达的影响,探讨其作用机制。方法: SD雄性大鼠24只,通过5/6肾切除法制备慢性肾衰竭模型,术后2周随机分为模型组、缬沙坦组,并设假手术组作为对照。术后第10周末测定各组大鼠血压及肾功能(BUN、Cr)后处死大鼠,取出心脏进行病理组织形态学观察;并采用原位杂交方法检测心肌ET-1mRNA转录水平。结果: 模型组术后第10周收缩压、心脏重量、心脏重量指数、左室重量及左室重量指数均明显增加,缬沙坦组能显著降低5/6肾切除大鼠收缩压、心脏重量、心脏重量指数、左室重量及左室重量指数(P<0.01);缬沙坦组心肌ET-1mRNA转录水平较模型组减弱。结论: 缬沙坦能改善慢性肾衰竭大鼠的左室肥厚,其机制可能是通过下调心肌ET-1 mRNA转录来实现的。

关键词: 缬沙坦, 慢性肾衰竭, 左室肥厚, 内皮素

Abstract: AIM: To observe the therapeutic effect of valsartan on cardiac hypertrophy and expression of endothelin-1(ET-1) in myocardium of rats with chronic renal failure and explore the mechanism.METHODS: 24 Sprague Dawley male rats were selected, and performed five-sixths nephrectomy to produce chronic renal failure model.Two weeks after the surgery, the rats were randomly divided into model group, valsartan group, and a sham group was established serving as control group.Systolic blood pressure, BUN and serum creatinine were measured at ten weeks after operation, then the rats were sacrificed to take the hearts for pathological histological examination.Hybridization in situ was used to examine the transcription of ET-1 mRNA in myocardium.RESULTS: Systolic pressure, heart weight, heart weight index, left ventricular weight mass(LVM) and left ventricular weight mass index (LVMI) in model group increased significantly tenth week after operation.Systolic pressure, heart weight, heart weight index, LVM and LVMI were decreased markedly in rats with five-sixths nephrectomy by valsartan(P<0.01);Hybridization in situ indicated that there was a decreasing expression of ET-1 mRNA in myocardium in valsartan group as compared with model group.CONCLUSION: Valsartan could prevent left ventricular hypertrophy in chronic experiment renal failure rats.The improvement of cardiomyopathy may be through the mechanism of downregulating transcription of ET-1 mRNA in myocardium.

Key words: valsartan, chronic renal failure, left ventricular hypertrophy, endothelin

中图分类号:

R965.1

徐海红, 杨利才, 杨沿浪, 张道友. 缬沙坦降低慢性肾衰竭大鼠心肌内皮素的表达[J]. 中国临床药理学与治疗学, 2008, 13(6): 639-643.

XU Hai-hong, YANG Li-cai, YANG Yan-lang, ZHANG Dao-you. Valsartan decrease expression of endothelin-1 in myocardium of rats with chronic renal failure[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(6): 639-643.

参考文献

[1] 王小时, 郑法雷, 刘燕萍. 慢性肾衰的心血管病变[M]//郑法雷, 章友康, 陈香美, 等主编. 肾脏病临床与进展. 北京:人民军医出版社, 2005:278-287.
[2] Shutov AM, Kondrat'eva NI, Kulikova ES, et al. Heart remodeling. In patients with predialysis phase of chronic renal failure[J]. Ter Arkh, 2000, 72(6): 46-49.
[3] London GM. Cardiovascular disease in chronic renal failure: pathophysiologic aspects[J]. Semin Dial, 2003, 16 (2): 85-94.
[4] Zolk O, Quattek J, Seeland U, et al. Activation of the cardiac endothelin system in left ventricular hypertrophy before onset of heart failure in TG(mREN2) 27 rats[J]. Cardiovasc Res, 2002, 53(2): 363-371.
[5] Ram CV. Possible therapeutic role of endothelin antagonists in cardiovasculardisease[J]. Am J Therapeutics, 2003, l0(6): 396-400.
[6] 秦旭平, 龙光, 徐立朋, 等. 氯沙坦和培哚普利逆转高血压大鼠心血管重构的比较[J]. 中国药理学通报, 2004, 20(10): 1107-1111.
[7] 王迎新, 李远思, 陈燕, 等. 福辛普利与氯沙坦对试验性糖尿病大鼠肾病的防治作用与转化因子β₁的关系[J]. 中国药理学通报, 2005, 21(7): 884-888.
[8] Piuhola J, Szokodi I, Kinnunen P, et al. Endothelin-1 contributes to the Frank-Starling response in hypertrophic rat hearts[J]. Hypertension, 2003, 41(1): 93-98.
[9] Schmieder RE. Endothelial dysfunction:how Can one intervene at the beginning of the cardiovascular continuum[J] ? J Hypertens Suppl, 2006, 24(2): S31-35.
[10] Nakamura K, Yamagishi S, Nakamura Y, et al. Telmisartan inhibitsexpression of a receptor for advanced glycation end products(RAGE) in anglotensin-II-exposed endothelial cells and decreases serum levels of soluble RAGE in patients with essential hypertension[J]. Microvasc Res, 2005, 70 (3): 137-141.
[11] Baba T, Kanda T, Kobay ashi I. Reduction of cardiac endothelin-1 by angiotensin II type 1 receptor antagonist in viral myocarditis of mice[J]. Life Sci, 2000, 67(5): 587-597.
[12] Naruse M, Tanabe A, Hara Y, et al. Effects of AT1 Receptor Antagonist and Spironolactone on Cardiac Expression of ET-1 mRNA in SHR-SP/Izm[J]. J Cardiovasc Pharmacol, 2004, 44: S1-S3.

[1]	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.
[2]	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.
[3]	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.
[4]	魏子寒，李栋博，元峥，陆颍，杨国杰. 沙库巴曲缬沙坦治疗左心疾病相关性肺动脉高压的临床研究[J]. 中国临床药理学与治疗学, 2019, 24(1): 57-62.
[5]	雍小兰，冯仕银，李楠，黄娟，王蓝天，康辉. 磷酸瑞格列汀和缬沙坦在健康人体的药代动力学相互作用研究[J]. 中国临床药理学与治疗学, 2016, 21(6): 661-666.
[6]	喻丽珍, 卞慧敏, 俞晶华. 六味地黄方对高脂血症大鼠血浆 ET、TXA₂、PGI₂水平及动脉内皮保护的影响[J]. 中国临床药理学与治疗学, 2014, 19(5): 503-506.
[7]	李培武, 王先坤, 种晓琴, 李培杰, 崔鸿斌, 鲁彦, 傅仲学. 孤束核微注射内皮素-1(1-31)对心血管活动的影响[J]. 中国临床药理学与治疗学, 2013, 18(7): 754-759.
[8]	李刚强, 阎伟, 巢胜吾, 樊济海. 原发性高血压患者中血管紧张素Ⅱ2型受体基因A1675G多态性与缬沙坦降压疗效的相关性研究[J]. 中国临床药理学与治疗学, 2012, 17(2): 185-188.
[9]	陈艾东, 李娟, 谢海棠. 内皮素心血管效应的研究进展[J]. 中国临床药理学与治疗学, 2011, 16(8): 937-944.
[10]	李玲, 谭志荣, 陈尧, 周淦, 郭栋, 严谨, 阳国平, 欧阳冬生. 快速灵敏的LC-MS/MS法测定人血浆中缬沙坦浓度[J]. 中国临床药理学与治疗学, 2010, 15(7): 809-813.
[11]	范晓, 徐杨, 张宏亮. 奥美拉唑对大鼠中毒性急性胃黏膜损伤的保护作用及机制[J]. 中国临床药理学与治疗学, 2010, 15(6): 626-630.
[12]	吴小冬, 张道友, 崔明春, 杨利才, 杨沿浪, 朱新俭. 缬沙坦与氟伐他汀单用及联用对阿霉素肾病大鼠血清肝细胞生长因子的影响[J]. 中国临床药理学与治疗学, 2010, 15(3): 305-309.
[13]	孙余明, 楼建涛, 黄光祥, 孙军. 注射用阿魏酸钠对胶原酶致大鼠脑出血模型的治疗作用及机制研究[J]. 中国临床药理学与治疗学, 2010, 15(12): 1377-1382.
[14]	茅尧生, 曹淼英, 周鑫. 强化胰岛素治疗对脓毒症患者血清血管性假血友病因子、内皮素1和一氧化氮浓度及预后的影响[J]. 中国临床药理学与治疗学, 2010, 15(12): 1414-1417.
[15]	王新, 杨玉雯, 王安才, 孔祥权. 缬沙坦干预对缺氧性肺动脉高压大鼠大电导钙激活钾通道的影响[J]. 中国临床药理学与治疗学, 2009, 14(9): 1032-1035.