七叶皂苷通过诱导自噬缓解化疗引起的外周神经病理性疼痛

Escin alleviates chemotherapy-induced peripheral neuropathic pain by inducing autophagy in the spinal cord of rats

目的探讨七叶皂苷对大鼠化疗所致外周神经病理性疼痛的作用及可能作用机制。方法将18只实验SD大鼠分为3组:七叶皂苷预处理组、七叶皂苷后处理组和对照组,6只/组。七叶皂苷预处理组的SD大鼠在CIPN造模前按照4 mg/kg予腹腔内注射七叶皂苷,注射7 d,注射1次/d;第8、10、12、14天腹腔内注射紫杉醇(2 mg/kg)。七叶皂苷后处理组的SD大鼠则先按照2 mg/kg腹腔内注射紫杉醇进行CIPN造模,于第1、3、5、7天注射;第8~14天按4 mg/kg予腹腔内注射七叶皂苷,注射1次/d。对照组的SD大鼠于第1、3、5、7天予紫杉醇腹腔内注射2 mg/kg,从第8天开始注射等体积的生理盐水,注射1次/d,连续注射至第14天。分别于第4、7、10、14天检测大鼠机械痛撤足阈值和热痛撤足潜伏期;采用Western blot检测大鼠脊髓组织中自噬相关蛋白LC3Ⅱ和p62的表达量。结果与对照组相比,预处理组大鼠机械痛和热痛阈值均升高(P<0.01);后处理组大鼠机械痛和热痛阈值较对照组升高(P<0.05)。Western blot结果显示,预处理组大鼠脊髓LC3Ⅱ的表达量较对照组升高,p62与对照组相比降低(P<0.05);后处理组大鼠脊髓LC3Ⅱ的表达量高于对照组,p62的表达量低于对照组(P<0.05)。结论七叶皂苷可能通过调节自噬相关蛋白的表达进而缓解化疗外周神经病理性疼痛。

Objective To investigate the effect of escin in relieving chemotherapy-induced peripheral neuropathic pain in rats and explore and the underlying mechanism.Methods Eighteen SD rats were randomly divided into 3 groups(n=6),including an escin preconditioning group(treated with 4 mg/kg escin on days 1-7 and then with 2 mg/kg taxol on days 8,10,12,and 14),an escin postconditioning group(treated with 2 mg/kg taxol on days 1,3,5,and 7 and then with 4 mg/mg escin on days 8-14)and control group(treated with 2 mg/kg taxol on days 1,3,5,and 7 and then with saline on days 8-14).Mechanical allodynia and thermal hyperalgesia of the mice were tested on days 4,7,10 and 14,and the expression levels of LC3II and p62 in the spinal cord of the rats were detected using Western blotting.Results The rats in both the escin preconditioning group and escin postconditioning group showed obviously increased thresholds of mechanical allodynia and thermal hyperalgesia as compared with those in the control group(P<0.01).Western blotting showed that the expression level of LC3II was significantly increased while p62 expression was lowered in escin preconditioning group as compared with those in the control group(P<0.05).The escin postconditioning group also showed significantly higher LC3II expression and lower p62 expression levels than the control group(P<0.05).Conclusion Escin can alleviate chemotherapy-induced peripheral neuropathic pain in rats possibly by upregulating the expressions of autophagy-related proteins in the spinal cord.