替米沙坦对非酒精性脂肪性肝炎大鼠模型抵抗素表达及胰岛素抵抗的影响
[Effects of telmisartan on resistin expression in a rat model of nonalcoholic steatohepatitis and insulin resistance].
作者信息
Zhang Qiuzan, Wang Yanrong, Liu Yingli, Yang Qian, Wang Xiuru, Wang Qiang, Zhang Chenming, Wang Bangmao
机构信息
Department of Gastroenterology, Tianjin Fourth Central Hospital, Tianjin Medical University the Fourth Central Clinical College, Tianjin 300140, China.
出版信息
Zhonghua Gan Zang Bing Za Zhi. 2015 Apr;23(4):281-5. doi: 10.3760/cma.j.issn.1007-3418.2015.04.010.
OBJECTIVE
To investigate the effects of telmisartan on expression of resistin in serum and liver under conditions of nonalcoholic steatohepatitis (NASH) and insulin resistance using a rat model system.
METHODS
Forty-five male Sprague-Dawley rats were randomly divided into a normal control group (NC, n=10), a model control group (MC, n=15), a polyene phosphatidylcholine prevention group (PP, n=10), and a telmisartan prevention group (TP, n=10). The NC group was given a standard diet and the other groups were given a high-fat diet for 16 weeks in order to induce NASH. At the end of week 12, 5 rats in the MC group were sacrificed for pathology confirmation of the NASH model. At the end of week 12, the TP group was given telmisartan (8.0 mg/kg/d) and the PP group was given polyene phosphatidylcholine (8.4 mg/kg/d) for an additional 4 weeks by intragastric administration. At the end of week 16, all rats were sacrificed and body weights recorded. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), resistin, insulin and fasting blood glucose were measured. The insulin resistance value, HOMA-IR, was assessed by homeostasis mode assessment. Liver expression of the resistin protein was detected by western blotting and of the resistin mRNA was detected by RT-PCR. The F test and LSD test were used for statistical analyses.
RESULTS
Compared to the NC group, the body weight and HOMA-IR of rats in the MC group were significantly increased (P<0.01). The levels of serum resistin, and of resistin protein and mRNA in liver, were significantly higher in the MC group than in the NC group of rats (all P less than 0.01). The body weight of rats in the TP group was significantly lower than those in the MC group (P<0.05). The levels of serrn resistin, resistin protein and mRNA in the liver, and insulin resistance were significantly lower in the TP group than in the MC group of rats (all P<0.01). The PP group did not show significant differences in any of these measures, except for loss of body weight (P<0.05).
CONCLUSION
Telmisartan elicits preventive and protective effects in a NASH rat model.Telmisartan may improve insulin resistance in NASH rats by decreasing the expression of serum resistin, and liver resistin protein and mRNA.
目的
利用大鼠模型系统，研究替米沙坦在非酒精性脂肪性肝炎（NASH）和胰岛素抵抗条件下对血清及肝脏中抵抗素表达的影响。
方法
45只雄性Sprague-Dawley大鼠随机分为正常对照组（NC，n = 10）、模型对照组（MC，n = 15）、多烯磷脂酰胆碱预防组（PP，n = 10）和替米沙坦预防组（TP，n = 10）。NC组给予标准饮食，其他组给予高脂饮食16周以诱导NASH。在第12周结束时，处死MC组的5只大鼠用于NASH模型的病理确认。在第12周结束时，TP组给予替米沙坦（8.0 mg/kg/d），PP组给予多烯磷脂酰胆碱（8.4 mg/kg/d），通过灌胃给药额外4周。在第16周结束时，处死所有大鼠并记录体重。检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆固醇（TC）、甘油三酯（TG）、抵抗素、胰岛素和空腹血糖水平。通过稳态模型评估法评估胰岛素抵抗值HOMA-IR。采用蛋白质印迹法检测肝脏中抵抗素蛋白的表达，采用逆转录聚合酶链反应（RT-PCR）检测抵抗素mRNA的表达。采用F检验和LSD检验进行统计学分析。
结果
与NC组相比，MC组大鼠的体重和HOMA-IR显著增加（P<0.01）。MC组大鼠血清抵抗素水平以及肝脏中抵抗素蛋白和mRNA水平均显著高于NC组大鼠（均P<0.01）。TP组大鼠的体重显著低于MC组（P<0.05）。TP组大鼠血清抵抗素水平、肝脏中抵抗素蛋白和mRNA水平以及胰岛素抵抗均显著低于MC组大鼠（均P<0.01）。PP组除体重减轻外（P<0.05），在这些指标上均未显示出显著差异。
结论
替米沙坦在NASH大鼠模型中具有预防和保护作用。替米沙坦可能通过降低血清抵抗素以及肝脏抵抗素蛋白和mRNA的表达来改善NASH大鼠的胰岛素抵抗。
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