补肾活血化瘀方上调雄激素致不孕大鼠脂肪组织中胰岛素受体底物1及其酪氨酸磷酰化

目的：研究雄激素致不孕大鼠（androgen sterilized rat，ASR）胰岛素受体底物1的表达及其酪氨酸磷酸化程度，探讨胰岛素抵抗（insulin resistance．IR）的分子机制和补肾活血化瘀方的作用机制。方法：ASR大鼠随机分为模型组、溶媒组（注射中性茶油）和补肾活血化瘀方组，各组均为15只大鼠。观察大鼠体质量和胰岛素曲线下面积．并检测大鼠脂肪组织中胰岛素受体底物1（insulin receptor substrate-1．IRS-1）的表达及其酪氨酸磷酸化程度。结果：模型组大鼠体质量和胰岛素曲线下面积高于溶媒组和补肾活血化瘀方组（P〈0.05）。模型组脂肪组织中IRS—1及其酪氨酸磷酸化程度低于溶媒组（P〈0.05）．补肾活血化瘀方组IRS—1的表达及其酪氧酸磷酸化程度上升．与模型组比较有统计学差异（P〈0.05）。结论：补肾活血化瘀方能促进IR大鼠脂肪组织IRS—1蛋白的表达及其酪氨酸磷酸化水平．这可能是其提高组织对胰岛素敏感性从而改善IR的机制之一。

Bushen Huoxue Huayu Recipe up-regulates expression of insulin receptor substrate-1 and phosphorylation of tyrosine in adipose tissue in androgen sterilized rats

OBJECTIVE: To investigate the expression of insulin receptor substrate-1 (IRS-1) and phosphorylation of tyrosine in androgen sterilized rats (ASRs) and the effects of Bushen Huoxue Huayu Recipe (BHHR), a compound Chinese herbal medicine for tonifying kidney and activating blood, on the ASRs, and to analyze the possible mechanism. METHODS: ASR models were established by means of testosterone injected subcutaneously at the age of 9 days. The model rats were randomly divided into BHHR group (n=15) and untreated group (n=15); the rats in normal group (n=15) were injected with oil. The rats in the BHHR group were treated with BHHR for 30 days, and the rats in model group and normal group were treated with distilled water for 30 days. Body weight and area under the curve (AUC) of insulin were measured after treatment. Expression of IRS-1 and phosphorylation of tyrosine in adipose tissue in ASRs were analysed by immunohistochemical method. RESULTS: The body weight and insulin AUC in the untreated group were increased and more than those in the BHHR group and the normal control group (P<0.05). Expression of IRS-1 and phosphorylation of tyrosine in normal group were significantly higher than those in the untreated group (P<0.05), and those in BHHR group were improved and significantly different from those in the untreated group (P<0.05). CONCLUSION: BHHR can increase the expression of IRS-1 and phosphorylation of tyrosine in adipose tissue in IR rats, which may be one of its mechanisms in improving insulin sensitivity of the target tissues.