我们的网站为什么显示成这样？

可能因为您的浏览器不支持样式，您可以更新您的浏览器到最新版本，以获取对此功能的支持，访问下面的网站，获取关于浏览器的信息：

|本期目录/Table of Contents|

雷帕霉素对大鼠心房纤维化的影响

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2013年第2期
页码:
180-184
栏目:
基础研究
出版日期:
2013-04-25

文章信息/Info

Title:
Effects of rapamycin on atrial fibrosis in rats
作者:
苏芳菊1; 张卫泽2; 张汉平2; 马 凌2; 陈永清2; 王智刚3; 鲍宏刚1
(1.第四军医大学西京医院心血管内科，陕西 西安 710032；2.兰州军区兰州总医院心内科，甘肃 兰州 730050；3.中铁二十局中心医院心脏病五科，陕西 咸阳 712000)
Author(s):
SU Fang-ju1;  ZHANG Wei-ze2;  ZHANG Han-ping2;  MA Ling2;  CHEN Yong-qing2;  WANG Zhi-gang3;  BAO Hong-gang1
(1.Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shanxi, China; 2.Department of Cardiology, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA, Lanzhou 730050, Gansu, China; 3.Cardiology Five Department of Central Hospital of Twentieth China Railway Bureau, Xianyang 712000, Shaanxi, China)
关键词:
雷帕霉素; 心房纤维化; 缺氧诱导因子-1; 转化生长因子-β1
Keywords:
sirolimus;  atrial fibrosis;  hypoxia inducible factor-1;  transforming growth factor-beta 1
分类号:
R979.5
DOI:
-
文献标识码:
A
摘要:
目的:探讨雷帕霉素(rapamycin，RAPA)对盐酸异丙肾上腺素(isoproterenol，ISO)诱导的大鼠心房纤维化的影响及其可能的机制。方法： 雄性Wistar 大鼠27只，随机分为空白对照组(对照组)、 ISO组和ISO+RAPA组，每组9只(n=9)。皮下注射ISO建立大鼠心房纤维化模型，给予RAPA干预。实验的第15天，处死大鼠并取心房组织，用放射免疫测定法检测AngⅡ的含量，用免疫组化染色法及Western blot法检测缺氧诱导因子-1α(hypoxia-inducible factor-1alpha，HIF-1α)和转化生长因子-β1(transforming growth factor-beta 1，TGF-β1)的表达。将心房组织切片经Masson染色后，观察心房纤维化程度即胶原容积分数(CVF)。结果： ①AngⅡ含量，与对照组(36.452±3.262) ng/L相比，ISO组(147.328±6.889) ng/L及ISO+RAPA组(142.252±4.968) ng/L明显升高(P<0.01)。对照组的CVF为(16.334±1.447)%，无心房纤维化，ISO组心房纤维化的程度明显(P<0.01)，ISO+RAPA组(17.021±1.341)%较ISO组(85.692±2.430)%心房纤维化的程度明显减轻(P<0.01)。②免疫组化染色法及Western blot的结果显示，ISO组HIF-1α(0.264±0.017) A和TGF-β1(0.343±0.018) A的表达较对照组［分别为(0.160±0.012) A和(0.129±0.012) A］均明显升高(P<0.01)，ISO+RAPA组［分别为(0.174±0.013) A和(0.139±0.014) A］较ISO组明显降低(P<0.01)，且与纤维化的程度呈正相关(r值分别0.949和0.987，P<0.01)；HIF-1α与TGF-β1的表达亦呈正相关(r值为0.945，P<0.01)。结论： RAPA可能通过抑制HIF-1α、TGF-β1的表达而使ISO诱导的大鼠心房纤维化减轻。
Abstract:
AIM:To explore the effects of rapamycin (RAPA) on atrial fibrosis in rats treated with high isoproterenol (ISO). METHODS: Twenty-seven male Wistar rats were randomly divided into control group, ISO group ［5 mg/(kg·day) for 7 days］ and ISO+RAP group ［3 mg/(kg·day) for 2 weeks］. Mice were sacrificed after 15 days. Angiotensin II (AngII) content in myocardial tissue was measured by radioimmunoassay, HIF-1α and TGF-β1 were detected by immunohistochemistry and Western blot, and atrial fibrosis was determined on H-E and Masson stained heart sections. RESULTS: Compared with the control group, AngII content increased in ISO group and ISO+RAP group (P<0.01). The degree of atrial fibrosis in ISO+RAP group was significantly lower than that in ISO group (P<0.01) and no atrial fibrosis was seen in control group. HIF-1α and TGF-β1 expressions of myocardium increased in ISO group compared with those in control group (P<0.01) and decreased in ISO+RAP group compared with those in ISO group (P<0.01). CONCLUSION: HIF-1α may be involved in atrial fibrosis and RAPA can efficiently improve atrial fibrosis by repressing the expressions of HIF-1α and TGF-β1.

参考文献/References

[1]Kramer S,Wang-Rosenke Y,Scholl V,et al.Low-dose mTOR inhibition by rapamycin attenuates progression in anti-thy1-induced chronic glomerulosclerosis of the rat[J].Am J Physiol Renal Physiol,2008,294(2):F440-F449.
[2]Zhu J,Wu J,Frizell E,et al.Rapamycin inhibits hepatic stellate cell proliferation in vitro and limits fibrogenesis in an in vivo model of liver fibrosis[J].Gastroenterology,1999,117(5):1198-1204.
[3]张卫泽,王智刚,陈永清,等.缬沙坦与U0126对大鼠心房纤维化和缝隙连接蛋白40重构的影响[J].中华心血管病杂志,201139(12):1129-1134.
[4]Goette A,Staack T,Rocken C,et al.Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation[J].J Am Coll Cardiol,2000,35(6):1669-1677.
[5]Li AC,Brown KK,Silvestre MJ,et al.Peroxisome proliferator-activated receptor gamma ligands inhibit development of atherosclerosis in LDL receptor-deficient mice[J].J Clin Invest,2000,106(4):523-531.
[6]Biecker E,De Gottardi A,Neef M,et al.Long-term treatment of bile duct-ligated rats with rapamycin (sirolimus) significantly attenuates liver fibrosis:analysis of the underlying mechanisms[J].J Pharmacol Exp Ther,2005,313(3):952-961.
[7]Wu MJ,Wen MC,Chiu YT,et al.Rapamycin attenuates unilateral ureteral obstruction-induced renal fibrosis[J].Kidney international,2006,69(11):2029-2036.
[8]唐 琳,郭 青,张翠翠,等.缺氧诱导因子1α介导的信号通路在血管紧张素Ⅱ诱导肾间质纤维化中的作用[J].中华肾脏病杂志,2011,27(3):194-197.
[9]宫丽崑,陈芳萍,戚新明,等.HIF-1α在博来霉素致大鼠肺纤维化中的作用[J].毒理学杂志,2005,19(3):259-260.
[10]徐叶进,陈永平,万 丽,等.缺氧诱导因子-1α在大鼠肝纤维化组织中的表达及其意义[J].中华传染病杂志,2008,26(11):651-655.
[11]Evans AJ,Russell RC,Roche O,et al.VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snail[J]. Mol Cell Biol,2007,27(1):157-169.
[12]Matsushita K,Y Wu,Okamoto Y,et al.Local renin angiotensin expression regulates human mesenchymal stem cell differentiation to adipocytes［J］. Hypertension,2006,48(6):1095-1102.
[13]Pan CH,Lin JL,Lai LP,et al.Downregulation of angiotensin converting enzyme II is associated with pacing-induced sustained atrial fibrillation[J].FEBS letters,2007,581(3):526-534.
[14]Jiang BH,Liu LZ.Role of mTOR in anticancer drug resistance: perspectives for improved drug treatment[J].Drug Resist Updat,2008,11(3):63-76.
15]Semenza GL.HIF-1:mediator of physiological and pathophysiological responses to hypoxia[J].J Appl Physiol,2000,88(4):1474-1480.
[16]Higgins DF,Kimura K,Bernhardt WM,et al.Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition[J].J Clin Invest,2007,117(12):3810-3820.

备注/Memo

备注/Memo:
收稿日期：2012-09-19.通讯作者：张卫泽，主任医师，主要从事冠心病研究 Email:zhangzwz@medmail.com.cn 作者简介：苏芳菊，硕士生 Email: nemohyx@163.com
更新日期/Last Update: 2013-04-28