天津医药

天津医药 ›› 2014, Vol. 42 ›› Issue (12): 1189-1192.doi: 10.3969/j.issn.0253-9896.2014.12.011

• 实验研究 • 上一篇    下一篇

替米沙坦对非酒精性脂肪性肝炎大鼠胰岛素抵抗及氧化应激的影响

刘应莉1,张秋瓒1,王艳荣1,2,杨倩1,2,付丽娜1,张静1   

  1. 1. 天津市第四中心医院
    2.
  • 收稿日期:2014-04-28 修回日期:2014-07-21 出版日期:2014-12-15 发布日期:2014-12-15
  • 通讯作者: 张秋瓒 E-mail:qiuzan_zh@sina.com
  • 基金资助:
    替米沙坦对非酒精性脂肪性肝炎大鼠保护机制的系列研究

Effects of Telmisartan on Insulin Resistance and Oxidative Stress in NonalcoholicSteatohepatitis Rats

Ying-LI LIU1,ZHANG Qiuzan 1,WANG Yanrong 2,3,YANG Qian 1,FU Lina 3,ZHANG Jing 3   

  • Received:2014-04-28 Revised:2014-07-21 Published:2014-12-15 Online:2014-12-15
  • Contact: ZHANG Qiuzan E-mail:qiuzan_zh@sina.com

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摘要：

【摘要】 目的 探讨替米沙坦对非酒精性脂肪性肝炎(NASH)大鼠血脂及氧化应激及胰岛素抵抗的影响。 方法 采用随机数字表法将 50 只雄性 SD 大鼠随机分为对照组、模型组、多烯磷脂酰胆碱组、替米沙坦低剂量组和替米沙坦高剂量组， 每组 10 只。 对照组以普通饲料喂养， 模型组和干预组给予高脂饲料喂养诱发 NASH， 12 周后， 分别给予生理盐水 1.0 mL/(kg·d)、生理盐水 1.0 mL/（kg·d）、多烯磷脂胆碱 8.4 mg/(kg·d)、替米沙坦 4 mg/(kg·d)和替米沙坦 8 mg/(kg·d)灌胃 4 周。 所有大鼠在第 16 周末处死， 测肝酶、血脂、氧化应激、胰岛素抵抗指数(HOMA-IR)等及肝组织 NAS 评分。 结果 与模型组比较， 多烯磷脂酰胆碱组丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）减低， NAS 评分改善； 替米沙坦低剂量组 AST 减低， 血清总抗氧化能力（T-AOC）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）、肝组织 SOD 和 GSH-PX 提高， 血清及肝组织 MDA 减低， HOMA-IR 减低， NAS 评分改善； 替米沙坦高剂量组 ALT 减低， 余指标变化同替米沙坦低剂量组。 结论 高剂量的替米沙坦可降低 NASH 大鼠肝酶、氧化应激、胰岛素抵抗和肝脏脂质沉积， 且作用优于多烯磷脂酰胆碱及低剂量替米沙坦。

关键词: 替米沙坦, 非酒精性脂肪性肝炎, 氧化应激, 胰岛素抵抗指数, 氧化性应激, 大鼠, Sprague-Dawley, 胰岛素抵抗

Abstract:

[Abstract] Objective To investigate the effects of telmisartan on insulin resistance and oxidative stress in nonalco? holic steatohepatitis (NASH) rats. Methods Fifty male SD rats were randomly divided into five groups: control group, mod? el group, polyene phosphatidylcholine group, low-dose telmisartan group and high-dose telmisartan group by using random number table (n=10 in each group). Control group was given standard food， the other groups were given high fat diet for 12weeks to establish NASH rat model. Then intervention groups were given either normal saline 1.0 mL/(kg· d) or polyene phos? phatidylcholine 8.4 mg/(kg· d), or telmisartan 4 mg/(kg· d) or telmisartan 8 mg/(kg· d) for 4 weeks by intragastric adminstra? tion． All rats were sacrificed at the end of the 16th week, the lever of plasma insulin resistance index (HOMA-IR), ALT, AST, TG, TC, MDA, SOD, T-AOC, CAT, GSH-PX and liver homogenate MDA, SOD, GSH-PX and liver NAS scores were tested. Results In polyene phosphatidylcholine treated group, the lever of plasma ALT, AST, HOMA-IR and liver NAS scores were degreased significantly compared with model group. The lever of plasma AST, SOD, T-AOC, CAT, GSH-PX and liver homogenate SOD, GSH-PX, liver NAS scores were improved in both low-dose and high-dose telmisartan groups com? pared with model group while plasma and liver homogenate MDA , HOMA-IR were reduced significantly in these two groups compared with model group. Besides, plasma ALT was significantly improved in high-dose telmisartan group compared with model group. Conclusion Telmisartan reduce plasma ALT, AST, oxidative stress, HOMA-IR and liver NAS scores in NASH rats. And high-does telmisartan is better than low-dose telmisartan and polyene phosphatidylcholine in treatment ef? fect.

Key words: telmisartan, nonalcoholic steatohepatitis, oxidative stress, insulin resistance index, oxidative stress, rats, Sprague-Dawley, insulin resistance