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目的观察鞘内注射甘珀酸(carbenoxolone,CBX)对腰5脊神经切断(L5 spinal nerve transaction,SNT)大鼠的镇痛作用及其相关机制。方法 60只♂SD大鼠,随机分成5组(n=12):Ⅰ.假手术组,Ⅱ.模型组,Ⅲ.SNT+CBX(0.05μg),Ⅳ.SNT+CBX(0.5μg),Ⅴ.SNT+CBX(5μg)。Ⅰ组仅暴露腰5脊神经,Ⅱ至Ⅴ组行SNT。术后10 d,Ⅰ和Ⅱ组鞘内注射生理盐水10μL,Ⅲ至Ⅴ组注射CBX 0.05μg(10μL)、0.5μg(10μL)和5μg(10μL),分别于术前1 d,术后1、3、5、7、10 d各组注射生理盐水和CBX,前1 h和给药后1、2、4、6 h测双侧机械痛阈值(mechanical withdrawl thresholds MWT),免疫组化及ELISA法观察给药后2h后脊髓背角胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)和TNF-α、IL-1β表达的变化。结果与术前相比,Ⅱ至Ⅴ组双侧MWT明显降低;与给药前1 h相比,Ⅱ和Ⅲ组给药后1、2、4、6 h双侧MWT均无明显差异;Ⅳ组损伤侧给药后1、2、4 h MWT无明显差异,而对侧MWT明显提高,同时该侧GFAP和TNF-α、IL-1β的表达也降低;Ⅴ组给药后1、2、4 h双侧MWT明显提高,双侧GFAP和TNF-α、IL-1β的表达也明显降低。结论鞘内注射CBX可缓解SNT大鼠双侧MWT,其机制可能与其抑制脊髓背角星形胶质细胞的活化及TNF-α和IL-1β释放减少有关。
Objective To observe the analgesic effects of intrathecal carbenoxolone (CBX) on lumbar 5 spinal nerve transaction (SNT) rats and its related mechanisms. Methods Sixty ♂ SD rats were randomly divided into five groups (n = 12): Ⅰ. Sham operation group, Ⅱ model group, Ⅲ.SNT + CBX (0.05μg), Ⅳ.SNT + CBX .SNT + CBX (5 μg). Group Ⅰ only exposed lumbar 5 spinal nerves, group Ⅱ to Ⅴ SNT. At 10 days after operation, rats in group Ⅰ and Ⅱ received intrathecal injection of 10 μL normal saline, and mice in groups Ⅲ andⅤ were injected with 0.05 μg (10 μL) of CBX, 0.5 μg (10 μL) and 5 μg (10 μL) Rats in each group were injected with normal saline and CBX on the 3rd, 5th, 10th and 10th days, mechanical withdrawl thresholds (MWT), immunohistochemistry and ELISA The changes of the expression of glial fibrillary acidic protein (GFAP), TNF-α and IL-1β in spinal dorsal horn were observed 2h after administration. Results Compared with those before operation, MWT in both groups was significantly lower than those in group Ⅱ to Ⅴ. There was no significant difference in MWT between two groups at 1, 2, 4 and 6 h after treatment At 1, 2 and 4 h after injury, there was no significant difference in MWT between MWT and MWT, while contralateral MWT was significantly increased, while the expression of GFAP, TNF-α and IL-1β in the group also decreased. 4h bilateral MWT was significantly increased, bilateral GFAP and TNF-α, IL-1β expression was significantly lower. Conclusion Intrathecal injection of CBX can relieve bilateral MWT in SNT rats. The mechanism may be related to its inhibition of activation of spinal cord astrocytes and reduction of TNF-α and IL-1β release.