红杉醇对2型糖尿病大鼠心肌NADPH氧化酶亚单位p22phox、p47phox及iNOS蛋白表达的影响

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (6): 626-631.

红杉醇对2型糖尿病大鼠心肌NADPH氧化酶亚单位p22phox、p47phox及iNOS蛋白表达的影响

许文奇, 李先伟, 郝伟, 刘艳, 杨解人

皖南医学院药理学教研室, 芜湖 241002, 安徽

收稿日期:2013-11-06 修回日期:2014-06-04 发布日期:2014-07-01
通讯作者: 杨解人, 女, 教授, 硕士生导师, 研究方向:心血管药理学。Tel: 0553-3932464 E-mail: wnmcyaoli@sina.com
作者简介:许文奇, 女, 硕士研究生, 研究方向:临床药理学。Tel: 13615534982 E-mail: 865053685@qq.com
基金资助:
安徽省教育厅高校省级优秀青年人才基金项目(2011SQRL105)

Effect of sequoyitol on the expression of NADPH oxidase p22phox, p47phox and iNOS protein in myocardium of type 2 diabetic rats

XU Wen-qi, LI Xian-wei, HAO Wei, LIU Yan, YANG Jie-ren

Department of Pharmacology, Wannan Medical College, Wuhu 241002, Anhui, China

Received:2013-11-06 Revised:2014-06-04 Published:2014-07-01

摘要/Abstract

摘要： 目的: 探讨红杉醇(sequoyitol, Seq)对2型糖尿病大鼠心肌烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶亚单位p22phox、p47phox 及诱导型一氧化氮合酶(iNOS)蛋白表达的影响。方法: 雄性SD大鼠100只, 分为正常组、模型组、Seq(12.5、25、50 mg/kg)及阿卡波糖(Aca, 20 mg/kg)组, 采用小剂量链脲佐菌素(STZ, 30 mg/kg)联合高糖高脂饲料建立2型糖尿病大鼠模型, HE染色观察心肌病理变化, Western Blot法检测心肌组织iNOS、p22phox及p47phox蛋白表达, 比色法检测心肌组织一氧化氮(NO)、过氧化氢(H₂O₂)、超氧化物歧化酶(SOD)及总抗氧化能力(T-AOC)的含量。结果: 与对照组相比, 模型组大鼠空腹血糖明显升高, 心肌肥厚明显加重, 心肌组织iNOS、p22phox及p47phox的表达水平及NO、H₂O₂含量显著升高, 而SOD和T-AOC水平明显降低。与模型组相比, Seq各剂量组和Aca组能不同程度地降低大鼠血糖, 改善糖尿病大鼠心肌损伤, 下调心肌iNOS、p22phox和p47phox的表达, 降低心肌NO、H₂O₂含量, 升高SOD、T-AOC水平。结论: Seq可能通过抑制心肌p22phox、p47phox及iNOS所介导的氧化应激损伤, 进而对糖尿病心肌损伤起到保护作用。

关键词: 红杉醇, 糖尿病大鼠, 诱导型一氧化氮合成酶, NADPH氧化酶, 氧化应激

Abstract: AIM : To investigate the effect of sequoyitol on the expression of NADPH oxidase p22phox, p47phox and iNOS protein in myocardium of type 2 diabetic rats.METHODS: Diabetic rats were induced by high-fat diet and low dose streptozotocin (30 mg/kg) and were administered with sequoyitol (12.5, 25 and 50 mg/kg) for 6 weeks. The changes in blood glucose (BG) and left ventricular mass index were calculated. Morphological change was observed by HE staining. We also measured nitric oxide (NO), hydrogen peroxide (H₂O₂), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) in myocardial tissue. In addition, the expression of NADPH oxidase p22phox, p47phox, and inducible nitric oxide synthase (iNOS) protein in myocardium were determined by Western Blot.RESULTS:Compared with the normal control group, the BG and left ventricular mass index were significantly increased. The levels of NO and H₂O₂ were significantly increased and the vitalities of SOD and T-AOC were obviously decreased. The expression of p22phox, p47phox, and iNOS were also significantly increased (P<0.01).Compared with the diabetic group, all above indexes of sequoyitol or acarbose treatment groups had been improved by gavage 6 weeks (P<0.05, P<0.01).CONCLUSION: These results showed that sequoyitol may be lessen the myocardial damage of diabetes by decreasing the expression of NADPH oxidase p22phox, p47phox and iNOS and reducing the sources of oxidative stress.

Key words: sequoyitol, diabetic rat, iNOS, NADPH oxidase, oxidative stress

中图分类号:

R965.2

许文奇, 李先伟, 郝伟, 刘艳, 杨解人. 红杉醇对2型糖尿病大鼠心肌NADPH氧化酶亚单位p22phox、p47phox及iNOS蛋白表达的影响[J]. 中国临床药理学与治疗学, 2014, 19(6): 626-631.

XU Wen-qi, LI Xian-wei, HAO Wei, LIU Yan, YANG Jie-ren. Effect of sequoyitol on the expression of NADPH oxidase p22phox, p47phox and iNOS protein in myocardium of type 2 diabetic rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(6): 626-631.

参考文献

[1] From AM, Scott CG, Chen HH.The development of heart failure in patients with diabetes mellitus and pre-clinical diastolic dysfunction a population-based study[J]. J Am Coll Cardio, 2010, 56(19):1612.
[2] Fang ZY, Prins JB, Marwick TH. Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications [J]. Endocr Rev, 2004, 25(4):543-567.
[3] Gao L, Huang W, Li J.NOX1 abet mesangial fibro genesis via iNOS induction in diabetes [J]. Mol Cell Biochem, 2013, 382(1/2):185-191.
[4] Shen H, Shao M, Cho KW, et al. Herbal constituent sequoyitol improves hyperglycemia and glucose intolerance by targeting hepatocytes, adipocytes, and β-cells [J]. Am J Physiol Endocrinol Metab, 2012, 302(8):932-940.
[5] Sivakumar S, Palsamy P, Subramanian SP. Attenuation of oxidative stress and alteration of hepatic tissue ultra structure by D-pinitol in streptozotocin-induced diabetic rats [J]. Free Radic Res, 2010, 44(6):668-678.
[6] Chen XP, Yang JR, Li XW, et al. Effects of sequoyitol on expression of NADPH oxidase subunits p22 phox and p47 phox in rats with type 2 diabetic liver disease [J]. Yao Xue Xue Bao, 2013, 48(4):489-494.
[7] Gurusamy N, Watanabe K, Ma M, et al. Glycogen synthase kinase 3beta together with 14-3-3 protein regulates diabetic cardiomyopathy: effect of losartan and tempol [J]. FEBS Lett, 2006, 580(8):1932-1940.
[8] Arozal W, Watanabe K, Veeraveedu PT, et al. Effects of angiotensin receptor blocker on oxidative stress and cardio-renal function in Streptozotocin-induced diabetic rats[J]. Biol Pharm Bull, 2009, 32(8):1411-1416.
[9] Newsholme P, Haber EP, Hirabara SM, et al. Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity [J]. J Physiol, 2007, 583(Pt 1): 9-24.
[10]Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: Role in cardiovascular biology and disease [J]. Circ Res, 2000, 86(5): 494-501.
[11]李佳伟, 郭志新.替米沙坦对2型糖尿病大鼠心肌NADPH氧化酶亚单位表达的影响[J].　解放军医学杂志, 2011, 10(36): 1037-1040.
[12]Adaikalakoteswari A, Balasubramanyam M, Rema M, et al. Differential gene expression of NADPH oxidase (p22phox) and hemoxygenase-1 in patients with Type 2 diabetes and microangiopathy [J]. Diabet Med, 2006, 23(6):666-674.
[13]Arstall MA, Sawyer DB, Fukazaw AR, et al. Cytokine-mediated apoptosis in cardiac myocytes: the role of inducible nitric oxide synthase induction and peroxynitrite generation [J]. Circ Res, 1999, 85(9): 829- 840.
[14]Li SH, Zhang HJ, Niu XM, et al. Chemical constituents from Amentotaxus yunnanensis and Torreyayunnanensis [J]. J Nat Prod, 2003, 66(7):1002-1005.

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