腹腔注射SRT1720对慢性坐骨神经结扎大鼠痛觉敏化和脊髓Sirt1表达∕活性的影响

目的 观察腹腔注射SRT1720对慢性坐骨神经结扎大鼠痛觉敏化和脊髓Sirt1表达/活性的影响。 方法 将96只SD大鼠随机分为6组:空白对照组(N组)、假手术组(Sham组)、坐骨神经慢性压迫损伤组(CCI组)、CCI+生理盐水注射组(CCI+NS组)、CCI+低剂量SRT1720(SRT1720 20 mg/kg腹腔注射)、CCI+高剂量组(SRT1720 50 mg/kg腹腔注射)。CCI模型建立后，分别通过微量注射器进行腹腔内注射2.5 ml/kg NS、20 mg/kg SRT1720、50 mg/g SRT1720，连续7 d。各组分别在术前和术后第1、3、5、7、10、14天用von Frey细丝测定大鼠的机械性缩足反射阈值(MWT)和热辐射法测定大鼠的热缩足潜伏期(TWL)，手术结束后提取大鼠脊髓测定Sirt1蛋白表达和去乙酰化酶活性。 结果 SRT720能抑制大鼠机械性缩足反射阈值和热缩足潜伏期，浓度越高，抑制越明显(P＜0.05)；SRT720能增加脊髓背角Sirt1蛋白表达，浓度越高，增加越明显(P＜0.05)；SRT720能增加脊髓背角Sirt1去乙酰化酶活性，浓度越高，增加越明显(P＜0.05)。 结论 腹腔注射SRT1720能抑制CCI大鼠的机械痛敏和热痛敏，其作用可能和增加脊髓Sirt1表达/活性有关。 

Effect of intraperitoneal injection of SRT1720 on nociceptor sensitization and expression and activity of Sirt1 in spinal cord of rats with chronic sciatic nerve constriction injury

Objective To observe the effect of intraperitoneal injection of SRT1720 on the nociceptor sensitization and expression and activity of Sirt1 in spinal cord of rats with chronic sciatic nerve constriction injury. Methods Total 96 case of SD rats were randomly divided into 6 groups:blank control group,sham operation group,chronic constriction injury(CCI) group of the sciatic nerve,CCI+saline injection group,CCI+low dose SRT1720 group,and CCI+high dose group.After the CCI model was established,NS 2.5 ml/kg,SRT1720 20 mg/kg and SRT1720 50 mg/kg were injected into the abdominal cavity through the micro syringe,for 7 consecutive days.The mechanical shrinkage foot reflex threshold(MWT) by von Frey filaments and thermal withdrawal latency(TWL) by heat radiation method were determined before the operation and at 1,3,5,7,10 and 14 d after the operation.The spinal cord was extracted surgically to test Sirt1 protein expression and deacetylase activity. Results SRT1720 could inhibit the mechanical paw withdrawal reflex threshold and thermal paw latency,and the inhibition was more significant with the increased concentration of SRT1720 (P<0.05);SRT1720 increased the expression of Sirt1 protein in the spinal dorsal horn,and the effect increased with the concentration of SRT1720(P<0.05);SRT1720 increased Sirt1 deacetylase activity in spinal dorsal horn,and increased with the concentration(P<0.05). Conclusion Intraperitoneal injection of SRT1720 can inhibit the mechanical and thermal pain sensitivity of CCI rats,which may be related to the increase of Sirt1 expression and activity in spinal cord.