金荞麦提取物改善肠易激综合征大鼠内脏痛觉过敏的效果及其机制

Effects of Fagopyrum cymosum extracts on visceral hyperalgesia of IBS rats and the mechanism

目的观察金荞麦提取物(Fag)对肠易激综合征(IBS)大鼠内脏痛觉过敏的影响及其机制。方法采用腹壁撤退反射(AWR)评分观察Fag(6、24 g·kg-1)口服给药两周后的IBS大鼠模型的内脏痛觉过敏的变化,并用免疫荧光法观察腰骶段脊髓背根神经(DRG)的辣椒素受体亚型TRPV1表达水平;采用细胞膜片钳记录Fag(0.1、0.3、1、3 g·L-1)对辣椒素(CAP)激活大鼠的DRG细胞TRPV1电流(ITRPV1)的影响。结果 Fag 24 g·kg-1在体内可显著降低升高的IBS大鼠AWR评分,IBS大鼠腰骶段DRG的TRPV1表达增高;Fag 6、24 g·kg-1干预后DRG的TRPV1表达下降;体外0.1、0.3、1、3 g·L-1Fag可浓度依赖地抑制CAP激活的分离DRG神经元ITRPV1,IC50为0.83 g·L-1。结论 Fag可通过下调IBS大鼠TRPV1受体表达改善大鼠痛觉过敏,可抑制DRG神经元ITRPV1峰值,调节痛觉信号传递。

OBJECTIVE To investigate the effects of Fagopyrum cymosum（ Trev.） Meisn extracts（ Fag） on visceral hyperalgesia of irritable bowel syndrome（ IBS） rats and the mechanism. METHODS In vivo,abdominal withdrawal reflex（ AWR） scoring system was employed to evaluate the visceral hyperalgesia of IBS rats after Fag（ 6,24 g·kg^-1） fed orally for 2 weeks. The expression of vanilloid receptor subunit TRPV1 in lumbosacral dorsal root ganglion（ DRG） was determined by immunofluorescence. In vitro,the effects of Fag（ 0. 1,0. 3,1,3 g·L^-1） on capsaicin（ CAP）- evoked TRPV1 current（ ITRPV1） were observed using whole- cell patch- clamp technique in isolated rat DRG neurons. RESULTS Fag 24 g·kg^-1could markedly reduce the elevated AWR scores in IBS rats. Moreover,TRPV1 level in lumbosacral DRG of IBS models has increased which could be decreased by Fag 6,24 g·kg^-1. While in vitro Fag（ 0. 1,0. 3,1,3g·L^-1） could inhibit ITRPV1 activated by CAP in DRG neurons in a concentration- dependent manner. Half inhibitory concentration（ IC50） of Fag was 0. 83 g·L^-1. CONCLUSIONS In vivo,Fag can exert therapeutic effects on hyperalgesia in IBS rats through down- regulation of TRPV1 expression; In vitro,Fag can modulate nociceptive transmission by inhibiting the peak of ITRPV1 in DRG neurons.