秦艽醇提物下调RhoA/ROCK通路发挥对神经根型颈椎病模型大鼠镇痛作用

目的:探讨秦艽醇提物调控Ras同源基因家族成员A(RhoA)/Rho相关卷曲螺旋形成蛋白激酶(ROCK)通路对神经根型颈椎病(cervical spondylotic radiculopathy,CSR)模型大鼠镇痛的影响机制。方法:建立CSR模型大鼠,随机分为模型组、秦艽醇提物(2 g·kg^-1)组、Rhosin(RhoA抑制剂,40 mg·kg^-1)组、秦艽醇提物(2 g·kg^-1)+Rhosin(40 mg·kg^-1)组4组(各12只),再选取12只大鼠作为假手术组,分组给药干预后,检测大鼠疼痛度、运动功能、血清炎性介质水平、脊髓及神经根组织病理形态及RhoA/ROCK通路相关蛋白表达。结果:与假手术组相比,模型组大鼠脊髓及神经根组织出现明显病理损伤,步态障碍评分、左前肢离地时间、脊髓及神经根组织RhoA、ROCK蛋白表达水平显著升高(P＜0.05),机械痛阈值、游泳时间显著降低(P＜0.05);模型大鼠经给药干预后其脊髓及神经根组织病理损伤均减轻,各指标水平变化减弱,相比秦艽醇提物、Rhosin单独干预,秦艽醇提物+Rhosin联合干预对模型大鼠作用更强。结论:秦艽醇提物可能通过下调RhoA/ROCK通路,抑制炎性介质合成释放,改善脊髓及神经根组织炎症损伤,减轻CSR大鼠疼痛,修复其神经运动功能。

Mechanisms of Gentiana macrophylla alcohol extract regulating RhoA/ROCK pathway on analgesia in rats with cervical spondylotic radiculopathy

OBJECTIVE To investigate the mechanism of Gentiana macrophylla alcohol extract regulating Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing kinase (ROCK) pathway on analgesia in cervical spondylotic radiculopathy (CSR) model rats.METHODS CSR model in rats was established, and the rats were randomly divided into model group, Gentiana macrophylla alcohol extract (2 g·kg^-1) group, Rhosin (RhoA inhibitor, 40 mg·kg^-1) group, and Gentiana macrophylla alcohol extract (2 g·kg^-1)+Rhosin (40 mg·kg^-1) group (12 per group), and another 12 rats were selected as the sham operation group. After administration intervention, the pain degree, motor function, serum inflammatory medium level, pathological morphology and expression of RhoA/ROCK pathway related proteins in spinal cord and nerve root were detected.RESULTS Compared with those in the sham operation group, the spinal cord and nerve root tissue showed obvious pathological damage, and the gait disorder score, time of left forelimb off the ground, spinal cord and nerve root tissue RhoA, ROCK protein expression levels were significantly increased (P＜0.05), and the mechanical pain threshold and swimming time were significantly reduced (P＜0.05); after administration intervention, the pathological injury of spinal cord and nerve root tissue of model rats was improved, and the changes of various indexes were weakened. Compared with the single intervention with Gentiana macrophylla alcohol extract or Rhosin, the combined intervention of Gentiana macrophylla alcohol extract and Rhosin had stronger effects in model rats.CONCLUSION Gentiana macrophylla alcohol extract may down-regulate RhoA/ROCK pathway, inhibit the synthesis and release of inflammatory mediators, improve the inflammatory damage of spinal cord and nerve root tissue, reduce pain in CSR rats, and repair their neuromotor function.