尿石素A通过抑制小胶质细胞激活缓解神经病理性疼痛*

Urolithin A alleviates neuropathic pain by inhibiting microglia activation*

摘要:

目的：探讨尿石素A (urolithin A，UA) 对慢性压迫性损伤模型 (chronic construction injury，CCI) 小鼠痛阈的影响及其可能机制。方法：选取C57BL/6J 8周雄性小鼠50只采用随机数字表法分为3组 (n = 10)：假手术组 (Sham组)、模型组 (CCI组) 和给药组 (CCI + UA组)。检测小鼠的机械刺激缩足反射阈值 (mechanical withdrawal threshold，MWT) 和热缩足反射潜伏期 (thermal withdrawal latency，TWL)；免疫荧光染色法观察脊髓背角Iba-1的表达；ELISA和Western Blot法检测脊髓背角TNF-α、IL-1β、IL-6的表达。结果：与Sham组相比，CCI组小鼠MWT和TWL均明显降低。与CCI组相比，CCI+UA组小鼠在造模后第7天MWT和TWL明显上升。与Sham组相比，CCI组小鼠Iba-1及TNF-α、IL-1β、IL-6的表达明显升高。与CCI组相比，CCI+UA组小鼠Iba-1和TNF-α、IL-1β、IL-6的表达升高被抑制。结论：UA能够有效缓解小鼠慢性神经病理性疼痛，其机制可能与抑制脊髓小胶质细胞激活及其炎症反应有关。

Abstract:

Objective: To investigate the effects of Urolithin A (urolithin A，UA) on the pain threshold of the mice with chronic construction injury (chronic construction injury，CCI) and its possible mechanism. Methods: Fifty male C57BL/6J mice at 8 weeks were selected and divided into 3 groups (n = 10): Sham group, CCI group, and CCI +UA group. The mechanical withdrawal threshold (mechanical withdrawal threshold，MWT) and thermal withdrawal latency (thermal withdrawal latency，TWL) were detected. Immunofluorescence staining was applied to observe the expression of Iba-1 in the spinal dorsal horn. The expressions of TNF-α, IL-1β and IL-6 in the spinal horn were detected by ELISA. Results: Compared with the Sham group, the MWT and TWL in the CCI group were significantly decreased. Compared with the CCI group, the MWT and TWL in CCI+UA group increased significantly on day 7 after operation. Compared with the Sham group, the expressions of Iba-1and pro-inflammatory factor TNF-α, IL-1β and IL-6 were significantly increased in CCI group. Compared with the CCI group, the expression of Iba-1 and TNF-α, IL-1β and IL-6 was inhibited in CCI+UA group. Conclusion: UA can relieve neuropathic pain, and its mechanism may be related to inhibiting the activation of spinal microglia and its inflammatory response.