摘要
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。
Aim To investigate the antagonistic effect of intrathecal injection of carbenoxolone( CBX) on neuropathic pain and its underlying mechanism. Methods Sixty male Sprague-Dawley rats were randomly divided into five groups( n = 12) : group I received sham surgery then treated with saline; group Ⅱ received SNT then treated with saline; group Ⅲ received SNT then treated with 0. 05 μg CBX; group Ⅳ received SNT then treated with 0. 5 μg CBX; group Ⅴreceived SNT then treated with 5 μg CBX. Treatment was undertaken with 10 μl volume as a single intrathecal injection on postoperative day 10. Mechanical withdrawl thresholds were measured 1d before operation,1,3,5,7 and 10 d after surgery,1 h before intrathecal administration,and 1,2,4,6 h after intrathecal administration. Lumbar spinal cord was obtained 2 h after intrathecal administration to determine the expressions of GFAP by immunohistology and TNF-α,IL-1βby ELISA in bilateral spinal dorsal horns. Results Compared with the sham group,the bilateral MWT in group Ⅱ ~ Ⅴ was significantly decreased. Compared with the MWT 1 h before intrathecal administration on day 10,the values at 1,2,4,6 h after administration of group Ⅱ and Ⅲ had no marked difference. The ipsilateral MWT in group Ⅳ had no significant difference at 1,2,4 h after administration, the contralateral MWT was significantly increased,whereas GFAP and TNF-α,IL-1β was significantly decreased in the spinal cord. In group Ⅴ the bilateral MWT was significantly improved at 1,2,4 h after administration,whereas GFAP and TNF-α,IL-1β were significantly decreased in the spinal cord. Conclusions Intrathecal CBX can inhibit the development of bilateral MWT. The analgesic effect of CBX is implemented partly via suppressing the actation of GFAP and the realease of TNF-α,IL-1βin the spinal doral horn.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2016年第6期863-867,共5页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 30901399)
