基于TLR4/NF-κB通路研究蒺藜总皂苷对周围神经病理性疼痛的镇痛作用

Analgesic effect of gross saponins from tribulus terrestris on peripheral neuropathic pain based on TLR4/NF-κB pathway

目的:基于TLR4/NF-κB通路研究蒺藜总皂苷(gross saponins from tribulus terrestris,GSTT)对大鼠慢性坐骨神经损伤(chronic constriction injury,CCI)所引起的周围神经病理性疼痛是否具有镇痛作用。方法:选取雄性SD大鼠40只,随机分为假手术组(SHAM组)、CCI组、GSTT 100 mg/kg+CCI组、GSTT 200 mg/kg+CCI组、普瑞巴林+CCI组(阳性对照)5组,每组8只。除SHAM组,其余各组均制备CCI大鼠模型,分别以药物处理后,检测各组大鼠机械缩足反射阈值(paw withdrawal mechanical threshold,PWMT)、热敏潜伏期;以HE染色检测各组大鼠脊髓及背根神经节组织病理形态变化;免疫组化检测脊髓及背根神经节组织中NF-κB的表达。结果:与SHAM组相比,CCI组大鼠PWMT、热敏潜伏期明显降低(P<0.05);损伤侧脊髓背角及背根神经节的神经元、胶质细胞染色较深,并出现肿胀、萎缩等损伤,细胞核浓缩、丢失;损伤侧脊髓背角及背根神经节中NF-κB表达水平明显增高(P<0.05)。与CCI组相比,GSTT 100 mg/kg+CCI组、200 mg/kg+CCI组,普瑞巴林+CCI组大鼠PWMT、热敏潜伏期升高(P<0.05),上述病理变化也明显改善,损伤侧脊髓背角及背根神经节中NF-κB水平降低。结论:GSTT对CCI大鼠引起的周围神经病理性疼痛具有镇痛作用,可能与TLR4/NF-κB通路有关。

Objective:To study the analgesic effect of gross saponins from tribulus terrestris(GSTT)on peripheral neuropathic pain caused by chronic constriction injury(CCI)in rats based on TLR4/NF-κB pathway.Methods:A total of 40 male SD rats were randomly divided into the SHAM group,CCI group,GSTT100mg/kg+CCI group,GSTT200mg/kg+CCI group and pregabalin+CCI group(positive control),with 8 rats in each group.Except SHAM group,CCI rat models were prepared in other 4 groups,paw withdrawal mechanical threshold(PWMT)and thermal latency were detected after being processed by drug respectively.HE staining was used to detect the pathological changes of spinal cord and dorsal root ganglion.The expression of NF-κB in spinal cord and dorsal root ganglion was detected by immunohistochemistry.Results:Compared with the SHAM group,PWMT and thermal latency of rats in the CCI group were significantly decreased and the differences were statistically significant(P<0.05).The neurons and glial cells in the posterior horn of the injured spinal cord and the dorsal root ganglion showed deep staining,swelling and atrophy,with concentration and loss of nucleus.The expression level of NF-κB in the posterior horn and dorsal root ganglion of the injured side was significantly increased.Compared with the CCI group,PWMT and thermal latency of rats in GSTT100 mg/kg+CCI group,200 mg/kg+CCI group and pregabali+CCI group were increased,and the differences were statistically significant(P<0.05).The above pathological changes were also significantly improved,and NF-κB level in posterior horn of spinal cord and dorsal root ganglion of injured side was decreased.Compared with the GSTT100 mg/kg+CCI group,the above pathological changes were further improved in the 200 mg/kg+CCI group and regabalin+CCI group,PWMT and thermal latency were significantly increased,and the differences were statistically significant(P<0.05).Meanwhile,NF-κB levels in the posterior horn of the injured side of the spinal cord and dorsal root ganglion were further reduced.Conclusion:GSTT has analgesic effect on peripheral neuropathic pain in CCI rats,which may be related to TLR4/NF-κB pathway.