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|

替米沙坦上调胰岛素抵抗大鼠心肌脂联素及其受体的表达

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2011年第2期
页码:
141-145
栏目:
基础研究
出版日期:
2010-12-10

文章信息/Info

Title:
Telmisartan upregulates expression of myocardial adiponectin and receptor in insulin-resistant rats
作者:
郭春艳李虹伟沈潞华赵树梅
首都医科大学附属北京友谊医院心内科,北京 100050
Author(s):
GUO Chun-yan LI Hong-wei SHEN Lu-hua ZHAO Shu-mei
Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
关键词:
脂联素心肌胰岛素抵抗受体替米沙坦
Keywords:
adiponectin cardiomyocyte insulin resistance receptor telmisartan
分类号:
R915
DOI:
-
文献标识码:
A
摘要:
目的: 探讨胰岛素抵抗(IR)大鼠心肌脂联素(APN)及其受体(AdipoR1和AdipoR2)表达改变和替米沙坦(TMST)的影响。方法: 雄性SD大鼠50只随机选择10只作为对照组(用普通饲料喂养8周),其余40只大鼠用高果糖饮食喂养4周建立IR模型。从IR大鼠中随机选择10只作为IR组(用生理盐水灌胃4周,继续用高果糖饮食喂养);另选10只作为TMST组[用替米沙坦5 mg/(kg·d)灌胃4周,继续用高果糖饮食喂养]。所有大鼠均于喂养的第8周末,空腹采血,分别采用ELISA法和放射免疫法测定血清APN和肿瘤坏死因子-α(TNF-α)的水平。采用Western blot法测定各组大鼠心肌组织中APN、AdipoR1、AdipoR2、过氧化物酶体增殖物激活受体-γ(PPARγ)及TNF-α蛋白的表达。结果: 实验第8周末,与对照组相比,IR组血清APN的水平降低 (P<0.01)而血清TNF-α的水平升高(P<0.01)。大鼠心肌中APN、AdipoR1及PPAR-γ蛋白的表达降低(P<0.01);心肌中TNF-α蛋白的表达增高(P<0.01),而心肌中AdipoR2蛋白的表达无明显变化。与IR组大鼠相比,TMST组大鼠血清APN增高(P<0.05)而血清TNF-α水平降低(P<0.05),心肌APN、AdipoR1及PPAR-γ蛋白的表达增高(P<0.05);心肌中TNF-α蛋白的表达降低(P<0.05),而心肌中AdipoR2蛋白的表达无明显变化。结论: IR大鼠心肌中APN及AdipoR1及PPARγ蛋白的表达降低;心肌中TNF-α蛋白的表达增高。TMST可通过激活PPARγ途径,增加循环中APN的水平,特别是激活心肌组织中的PPARγ,减轻炎症,提高APN及其受体的表达。
Abstract:
AIM: To explore expression of myocardial adiponectin and its receptors in insulin-resistant (IR) rats and to study the effect of telmisartan (TMST). METHODS: Fifty male Sprague Dawley rats were included in the study, ten of whom were put in group C and were fed with ordinary diet for 8 weeks. The other 40 rats were fed with a high-fructose diet for 4 weeks to induce IR rat model. Ten IR rats were selected as IR group and were fed with high-fructose diet and treated with 0.9% saline for the next 4 weeks. Another 10 IR rats were selected as TMST group and were fed with high-fructose diet and treated with telmisartan 5 mg/(kg·day) for the next 4 weeks. After 8 weeks, blood samples were obtained and APN and TNF-α were measured. Protein expressions of myocardial APN, AdipoR1, AdipoR2, PPARγ and TNF-α were detected by Western blot. RESULTS: Compared with those in group C, serum APN decreased and TNF-α level increased in IR group. Compared with those in IR group, serum APN increased and serum TNF-α level decreased in TMST group. Protein expressions of myocardial APN, AdipoR1 and PPARγ were attenuated with enhanced TNF-α in IR group compared with those in group C. Protein expressions of myocardial APN, AdipoR1 and PPARγ were enhanced with attenuated TNF-α in TMST group compared with those in IR group. CONCLUSION: In IR rats, myocardial protein expressions of APN, AdipoR1 and PPARγ decreased and myocardial protein expressions of TNF-α increased. TMST can increase the myocardial expressions of adiponectin AdipoR1 and PPARγ and reduce inflammation.

参考文献/References

[1]Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity[J].Nat Med, 2001, 7(8):941-946.

[2]Ouchi N, Kihara S, Arita Y, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-κB signaling through a cAMP-dependent pathway[J].Circulation, 2000, 102(11):1296-1301.

[3]Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages[J]. Circulation, 2001, 103(8):1057-1063.

[4]Mao X, Kikani CK, Riojas RA, et al. APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function[J]. Nat Cell Biol, 2006, 8(5):516-523.

[5]Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects[J]. Nature, 2003, 423(6941):762-769.

[6]Pi?eiro R, Iglesias MJ, Gallego R, et al. Adiponectin is synthesized and secreted by human and murine cardiomyocytes[J]. FEBS Lett, 2005, 579(23):5163-5169.

[7]Pershadsingh HA, Kurtz TW. Insulin-sensitizing effects of telmisartan: implications for treating insulin-resistant hypertension and cardiovascular disease[J]. Diabetes Care, 2004, 27(4):1015.

[8]Schupp M, Clemenz M, Gineste R, et al. Molecular characterization of new selective peroxisome proliferator?activated receptor gamma modulators with angiotensin receptor blocking activity[J]. Diabetes, 2005, 54(12):3442-3452.

[9]Sugimoto K, Qi NR, Kazdova L, et al. Telmisartan but not valsartan increases caloric expenditure and protects against weight gain and hepatic steatosis[J]. Hypertension, 2006, 47(5):1003-1009.

[10]Reaven GM, Hwang IS, Ho H. Fructose induced insulin resistance and hypertension in rats[J]. Hypertension, 1987, 10(5):512-516.

[11]李光伟,潘孝仁,Stephen L,等. 检测人群胰岛素敏感性一项新指标[J]. 中华内科杂志, 1993, 32(10):656-660.

[12]Benson SC, Pershadsingh HA, Ho CI, et al. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity[J]. Hypertension, 2004, 43(5):993-1002.

[13]Skurk C, Wittchen F, Suckau L, et al. Description of a local cardiac adiponectin system and its deregulation in dilated cardiomyopathy[J]. Eur Heart J, 2008, 29(9):1168-1180.

[14]Fujioka D, Kawabata K, Saito Y, et al. Role of adiponectin receptors in endothelin-induced cellular hypertrophy in cultured cardiomyocytes and their expression in infarcted heart[J]. Am J Physiol Heart Circ Physiol, 2006, 290(6):H2409-H2416.

[15]Inukai K, Nakashima Y, Watanable M, et al. Regulation of adiponectin receptor gene expression in diabetic mice[J]. Am J Physiol Endocrinol Metab, 2005, 288(5):E876-E882.

[16]Tan GD, Debard C, Funahashi T, et al. Changes in adiponectin receptor expression in muscle and adipose tissue of type 2 diabetic patients during rosiglitazone therapy[J]. Diabetologia, 2005, 48(8):1585-1589.

[17]Hirose H, Kawai T, Yamamoto Y, et al. Effects of pioglitazone on metabolic parameters, body fat distribution, and serum adiponectin levels in Japanese male patients with type 2 diabetes[J].Metabolism, 2002, 51(3):314-317.

[18]Ding G, Qin Q, He N, et al. Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor gamma[J]. J Mol Cell Cardiol, 2007, 43(1):73-84.

[19]Maeda N, Takahashi M, Funahashi T, et al. PPARgamma ligands increase expression and plasmaconcentrations of adiponectin, an adipose-derived protein[J]. Diabetes, 2001, 50(9):2094-2099.

[20]Fujimoto M, Masuzaki H, Tanaka T, et al. An angiotensin II AT1 receptor antagonist, telmisartan augments glucose uptake and GLUT4 protein expression in 3T3-L1 adipocytes[J]. FEBS Lett, 2004, 576(3):492-497.

[21]Clasen R, Schupp M, Foryst-Ludwig A, et al. PPARgamma-activating angiotensin type-1 receptor blockers induce adiponectin[J].Hypertension, 2005, 46(1):137-143.

备注/Memo

备注/Memo:
收稿日期:2010-04-15.基金项目:北京市自然科学基金项目资助(7082027) 通讯作者:李虹伟,主任医师,主要从事心血管疾病及代谢综合征防治的研究Email:mcw19656@yahoo.com.cn 作者简介:郭春艳,主治医师,博士Email:cardiovas@hotmail.com
更新日期/Last Update: 2010-12-10