替米沙坦对胰岛素抵抗大鼠胰岛蛋白酪氨酸磷酸酶1B表达的影响

Effect of different doses of telmisartan on the expression of protein tyrosine phosphatase-1B in islet of rats with insulin resistance

目的观察不同剂量替米沙坦对高糖高脂膳食诱导的胰岛素抵抗大鼠胰岛蛋白酪氨酸磷酸酶1B(PTP-1B)表达的影响,探讨替米沙坦保护胰岛功能的机制。方法6-8周龄雄性SD大鼠40只随机分为对照组NC组、高糖高脂组(HSHF组)、替米沙坦5 mg组(T5 mg组)、替米沙坦10 mg组(T10 mg组),每组10只。NC组饲予普通饲料,其余组饲予HSHF饲料。第24周末,NC组继续饲予普通饲料并灌胃给予2 ml生理盐水,HSHF组继续饲予HSHF饲料并灌胃给予2 ml生理盐水,T5 mg组和T10 mg组继续饲予HSHF饲料并分别灌胃给予溶于2 ml生理盐水的替米沙坦5 mg/(kg·d)和10 mg/(kg·d),以上处理均持续12周,灌胃1次/d。第36周末,测定空腹血浆葡萄糖(FPG)、空腹胰岛素(FINS)、甘油三酯(TG),计算胰岛素抵抗指数(HOMA-IR),免疫组化法检测胰岛PTP-1B的表达。结果与NC组比较,HSHF组大鼠的FPG、FINS、TG水平及HOMA-IR均显著升高(P<0.05)。与HSHF组比较,T5 mg组和T10 mg组大鼠的FPG、FINS、TG水平及HOMA-IR均显著降低(P<0.05),且T5 mg组和T10 mg组间指标也有统计学差异。与NC组比较,HSHF组大鼠胰岛PTP-1B表达显著升高(P<0.05),T5 mg组和T10 mg组胰岛PTP-1B表达显著降低(P<0.05),且T10 mg组更低。结论替米沙坦可下调胰岛素抵抗大鼠胰岛PTP-1B的表达,这可能是其改善胰岛素抵抗大鼠糖代谢、保护胰岛功能的机制之一。

Objective To observe the effect of different doses of telmisartan on the expression of protein tyrosine phosphatase-1B(PTP-1B)in islet of rats with insulin resistance induced by long-term high sugar and high fat diet,and to explore the mechanism of telmisartan protecting islet function.Methods The male SD rats were randomly divided into four groups:normal control group(NC group),high sugar and high fat group(HSHF group),telmisartan 5 mg group(T5 mg group)and telmisartan 10 mg group(T10 mg group).The rats were fed with normal diet in NC group,and HSHF diet in the other three groups.At the end of the 24th week,the rats were continuously given normal diet and gavaged with 2 ml normal saline in NC group,the rats were continuously given HSHF diet and gavaged with 2 ml normal saline in HSHF group,and the rats in were continuously given HSHF diet and gavaged with 5 mg/(kg·d)telmisartan or 10 mg/(kg·d)in T5 mg group and T10 mg group.The above treatment lasted for 12 weeks and once per day.At the end of the 36th week,fasting blood glucose,fasting insulin and triglyceride were examined,insulin resistance index was calculated(HOMA-IR=FPG×FINS/22.5),and the expression level of PTP-1B in rat islet was detected by immunohistochemical method.Results Compared with NC group,the levels of FBG,FINS,TG and HOMA-IR in HSHF group were significantly increased(P<0.05).The level of FBG,FINS,TG and HOMA-IR in T5 mg group and T10 mg group were significantly lower than those in HSHF group(P<0.05),and there was significant difference between T5 mg group and T10 mg group.The expression of PTP-1B in HSHF group was significantly higher than that in NC group(P<0.05),and the expression of PTP-1B in T5 mg group and T10 mg group was significantly lower than that in HSHF group(P<0.05),and it was lower in T10 mg group than in T5 mg group.Conclusion Telmisartan can down-regulate the expression of PTP-1B on islet,which may be one of the mechanisms of improving glucose metabolism and protecting islet function in rats with insulin resistance.