吡格列酮改善代谢综合征大鼠肝脏氧化和硝化应激

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (9): 988-992.

吡格列酮改善代谢综合征大鼠肝脏氧化和硝化应激

张妍, 袁鹤鸣, 韩真

皖南医学院附属弋矶山医院消化内科,芜湖 241001,安徽

收稿日期:2012-11-09 修回日期:2013-06-05 发布日期:2013-09-07
通讯作者: 袁鹤鸣,男,本科,副主任医师,研究方向:消化系疾病的临床及内镜诊治。E-mail: yhm6186@sina.com
作者简介:张妍,女,硕士,主治医师,研究方向:消化系疾病的临床及内镜诊治。Tel: 13805530026 E-mail: yanyan0921@sina.com
基金资助:
安徽省教育厅自然科学基金项目(KJ2010B466);皖南医学院中青年科研基金项目(WK200911F)

Pioglitazone improves hepatic oxidative and nitrative stress in metabolic syndrome rats

ZHANG Yan, YUAN He-ming, HAN Zhen

Department of Gastroenterology, Yijishan Hospital Affiliated to Wannan Medical College, Wuhu 241001, Anhui,China

Received:2012-11-09 Revised:2013-06-05 Published:2013-09-07

摘要/Abstract

摘要： 目的: 探讨吡格列酮(Pio)改善代谢综合症(MS)大鼠肝脏损伤的作用机制。方法: 7周龄SD大鼠喂饲高脂高盐饲料和20%蔗糖饮水16周,于第8周开始灌服不同剂量Pio(10和 3 mg·kg^-1·d^-1)至实验结束。测定尾动脉SBP;称肝脏湿重(LW),计算其占体重比值(LW/BW);测空腹血糖(FBG)、ALT、AST、血脂和胰岛素(FIns)水平,计算稳态胰岛素评价指数(HOMA-IR);测肝脏组织总抗氧化能力(T-AOC)、丙二醛(MDA)含量、诱导型一氧化氮合酶(iNOS)和抗氧化酶活性;测定肝脏硝基酪氨酸(NT)蛋白水平;HE染色观察肝脏病理变化。结果: 与模型组相比,Pio治疗后SBP、LW、LW/BW、ALT、AST、血脂、FIns和HOMA-IR显著降低(P<0.05);肝脏T-AOC和超氧化物歧化酶(SOD)活性增高,MDA含量、iNOS活性和NT蛋白水平显著减少(P<0.05);肝脏病理损伤显著改善。结论: Pio显著改善MS大鼠肝脏功能和结构损伤,此作用与改善氧化和硝化应激状态有关。

关键词: 吡格列酮, 代谢综合症, 氧化应激, 硝化应激

Abstract: AIM: To investigate the possible in vivo protective effects of pioglitazone (Pio) on hepatic lesions in metabolic syndrome (MS) rats.METHODS: Normal 7-week-old SD rats were fed with a high-fat, high-salt diet plus 20% sucrose solution for 16 weeks. Pio (10 and 3 mg·kg^-1·d^-1) was orally administered in MS rats from 8 weeks to the end of this study. Systolic blood pressure (SBP) was measured monthly. Liver wet weight (LW) was recorded and liver weight/body weight (LW/BW) ratio was calculated. Levels of fasting blood glucose (FBG), alanine aminotranferease (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), fasting insulin (FIns) were determined. Insulin resistance (HOMA-IR) was calculated. Hepatic total-antioxidant capacity (T-AOC), malondialdehyde (MDA) content, inducible nitric oxide synthase (iNOS) and antioxidant enzyme activities, and protein level of nitrotyrosine (NT) were measured. In addition, pathological changes were observed with HE staining.RESULTS: Compared with MS rats, treatment with Pio decreasd the SBP, LW, LW/BW, ALT, AST, TC, TG, FIns and HOMA-IR(P<0.05). Furthermore, treatment with Pio enhanced the hepatic T-AOC and SOD activity, reduced the iNOS activity and protein level of NT(P<0.05), and obviously ameliorated hepatic pathologic lesions.CONCLUSION: Pio improves lesions of hepatic structure and function in MS rats through alleviation of oxidative and nitrative stress.

Key words: Pioglitazone, Metabolic syndrome, Oxidative stress, Nitrative stress

中图分类号:

R965.2

张妍, 袁鹤鸣, 韩真. 吡格列酮改善代谢综合征大鼠肝脏氧化和硝化应激[J]. 中国临床药理学与治疗学, 2013, 18(9): 988-992.

ZHANG Yan, YUAN He-ming, HAN Zhen. Pioglitazone improves hepatic oxidative and nitrative stress in metabolic syndrome rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(9): 988-992.

参考文献

[1] Karl F, Johannes F. The choice of antihypertensive therapy in patients with the metabolic syndrome-time to change recommendations [J]. Nephrol Dial Transplant, 2008, 23(11): 3389-3391.
[2] Marchesini G, Bugiansi E, Forlani G, et al. Nonalcobolic fatty liver, steatohepatitis and the metabolic syndrome [J]. Hepatology, 2003, 37(4): 917-923.
[3] Promrat K, Lutchman G, Uwaifo GI, et a1. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis [J]. Hepatology, 2004, 39(1): 188-196.
[4] Belfort R, Harrison SA, Brown K, et a1. A Placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis [J]. N Engl J Med, 2006, 355(22): 2297-2307.
[5] Dobrian AD, Schriver SD, Khraibi AA, et a1. Pioglitazone prevents hypertension and reduces oxidative stress in diet-induced obesity [J]. Hypertension, 2004, 43(1): 48-56.
[6] Saiki R, Okazaki M, Iwai S, et a1. Effects of pioglitazone on increases in visceral fat accumulation and oxidative stress in spontaneously hypertensive hyperlipidemic rats fed a high-fat diet and sucrose solution [J]. J Pharmacol Sci, 2007, 105(2): 157-167.
[7] Namikoshi T, Satoh M, Tomita N, et a1. Pioglitazone ameliorates endothelial dysfunction in obese rats with nephropathy [J]. Biochem Biophys Res Commun, 2007, 361(4): 835-840.
[8] Haddad JJ, Harb HL. L-gamma-Glutamyl-L-cysteinyl-glycine (glutathione; GSH) and GSH-related enzymes in the regulation of pro- and anti-inflammatory cytokines: a signaling transcriptional scenario for redox(y) immunologic sensor(s) [J]. Mol Immunol, 2005, 42(9): 987-1014.
[9] Kong X, Zhang DY, Wu HB, et al. Losartan and pioglitazone ameliorate nephropathy in experimental metabolic syndrome rats [J]. Biol Pharm Bull, 2011, 34(5): 693-699.
[10] 孔祥, 张道友, 张妍, 等. 氧化应激在高脂高盐饮食伴高糖饮水诱导的代谢综合征肾病大鼠中的作用研究 [J]. 中国病理生理杂志, 2011, 27(11): 2160-2164.
[11] Roberts CK, Barnard RJ, Sindhu RK, et al. Oxidative stress and dysregulation of NAD(P)H oxidase and antioxidant enzymes in diet-induced metabolic syndrome [J]. Metabolism, 2006, 55(7): 928-934.
[12] 郭莉群, 杨解人, 孔祥. 芝麻素对代谢综合征性脂肪肝大鼠肝组织iNOS和NT表达的影响 [J]. 中国病理生理杂志, 2010, 26(2): 337-340.

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