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

Effects of Telmisartan on Insulin Resistance and Oxidative Stress in Nonalcoholic Steatohepatitis Rats

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 m L/(kg·d)、生理盐水1.0 m L/(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。

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 randomnumber table（n=10 in each group）. Control group was given standard food,the other groups were given high fat diet for 12 weeks to establish NASH rat model. Then intervention groups were given either normal saline 1.0 m L/（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 16 th 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 weretested. Results In polyene phosphatidylcholine treated group, the lever of plasma ALT, AST, HOMA-IR and liver NASscores were degreased significantly compared with model group. The lever of plasma AST, SOD, T-AOC, CAT, GSH-PX andliver 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 groupscompared with model group. Besides, plasma ALT was significantly improved in high-dose telmisartan group compared withmodel group. Conclusion Telmisartan reduce plasma ALT, AST, oxidative stress, HOMA- IR and liver NAS scores inNASH rats. And high-does telmisartan is better than low-dose telmisartan and polyene phosphatidylcholine in treatment ef-fect.