雷帕霉素对大鼠糖尿病神经痛作用的研究

目的：研究链脲佐菌素（streptozotoccin ，STZ）诱导的糖尿病神经痛（DNP）大鼠脊髓哺乳动物雷帕霉素靶蛋白（mam‐malian target of rapamycin ，mTOR）的变化，及其特异性阻断剂雷帕霉素的干预作用。方法痛阈正常的健康成年雄性SD大鼠40只，随机取30只，尾静脉注射STZ（60 mg／kg），一周后尾静脉采血血糖大于16．7 mmol／L者视为糖尿病造模成功。测定后足缩足反射阈值，将痛觉过敏者随机分为DNP组和RAP组，其中RAP组每日腹腔注射雷帕霉素5 mg／kg。给药14 d后，测定各组血糖及后足缩足反射阈值，并取L4／5段脊髓检测mTOR及S6K蛋白表达。结果糖尿病神经痛大鼠脊髓mTOR和S6K磷酸化水平升高，给予雷帕霉素14 d后，两者磷酸化水平明显降低，同时痛觉过敏得到显著改善。结论脊髓mTOR可能参与了大鼠糖尿病神经痛的发病，其特异性阻断剂雷帕霉素可以减轻其症状。

Effect of rapamycin on rat models of diabetic neuropathic pain

Objective To investigate the effect and mechanism of rapamycin on STZ‐induced rat models of diabetic neuropathic pain .Methods Here ,the effect of repamycin ,a selective inhibitor of mTOR was investigated on a rat model of diabetic neuropathic pain .Male Sprague‐Dawley rats were randomly divided into three groups :the control group ,the diabetic neuropathic pain group and the rapamycin treatment group .Diabetes was induced by intraperitoneal streptozotocin (60mg/kg) ,and confirmed by measurement of serum glucose levels 7 days after injection .Mechanical withdrawal threshold to von Frey filament stimulation was measured 4 weeks after induction of diabetes ,and the L4/5 spinal cord was assayed for the expression of mTOR and its downstream effector S6K1 using western blot .Results The expression of phosphorylated mTOR and S6K1 was significantly increased in the L4/5 spi‐nal cord 4 weeks after STZ injection ,indicating mTOR activation .While inhibition of mTOR by intraperitoneal injection of rapamy‐cin led to a decrease in hyperalgesia .Conclusion The data revealed that rapamycin has protective effects against diabetic neuropath‐ic pain which are related to the inhibition of mTOR up‐regulation in spinal cord .