补阳还五汤对大鼠化疗相关外周神经痛的预防作用及其机制

目的观察补阳还五汤对紫杉醇诱导的大鼠外周神经痛的预防作用,并以脊髓大麻素受体为主要靶点,探讨其作用机制。方法将50只SD大鼠随机分为对照组、模型组、预防组、AM630组、AM251组,每组10只。除对照组外,其余各组于实验第1,3,5,7天分别腹腔注射紫杉醇2 mg/kg;预防组在建模的同时每天予补阳还五汤2.5 g/(kg·d)灌胃干预14 d;AM630组在预防组的基础上于每天灌胃前予3 mg/kg大麻素Ⅱ型受体(CBR2)阻滞剂AM630腹腔注射;AM251组在预防组的基础上于每天灌胃前予1.5 mg/kg大麻素Ⅰ型受体(CBR1)阻滞剂AM251腹腔注射。每7 d记录1次各组大鼠体质量,并使用von fery纤维丝测试各组大鼠机械缩足阈值(MWT),共观察28 d;实验观察28 d后使用RT-PCR检测各组大鼠脊髓组织中CBR1、CBR2、胶质纤维酸性蛋白(GFAP)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的mRNA表达水平。结果实验第7,14,21,28天,各组大鼠体质量增量比较差异均无统计学意义(P均>0.05)。模型组实验第7,14,21,28天的MWT均显著低于同期对照组(P均<0.05);预防组、AM251组实验第14,21,28天的MWT均显著高于同期模型组(P均<0.05),但AM630组与模型组比较、预防组与AM251组比较差异均无统计学意义(P均>0.05)。模型组CBR2、CBR1、GFAP mRNA表达水平与对照组比较差异均无统计学意义(P均>0.05),IL-1β、TNF-αmRNA表达水平明显高于对照组(P均<0.05);预防组和AM251组CBR2 mRNA表达水平明显高于模型组(P均<0.05),IL-1β、TNF-αmRNA表达水平均明显低于模型组(P均<0.05);AM630组与模型组比较、预防组与AM251组比较各相关蛋白mRNA表达水平差异均无统计学意义(P均>0.05)。结论补阳还五汤可以预防紫杉醇诱导的外周神经痛,机制可能与其激活脊髓CBR2,并进一步抑制脊髓IL-1β、TNF-α等炎症细胞因子的表达有关。

Preventive effect of Buyang Huanwu Decoction on chemotherapy-related peripheral neuralgia in rats and its mechanism

Objective It is to observe the preventive effect of Buyang Huanwu Decoction on paclitaxel-induced peripheral neuralgia in rats,and to take the cannabinoid receptor of the spinal cord as the main target to explore its mechanism of action.Methods Fifty SD rats were randomly divided into control group,model group,prevention group,AM630 group and AM251 group,with 10 rats in each group.Except for the control group,the other groups were intraperitoneally injected with paclitaxel 2 mg/kg on the 1st,3rd,5th,and 7th days of the experiment;the prevention group was treated with Buyang Huanwu Decoction 2.5 g/(kg·d)by intragastric administration every day for 14 days while modeling.AM630 group was intraperitoneally injected with 3 mg/kg cannabinoid type II receptor(CBR2)blocker AM630 before daily gavage on the basis of prevention group.AM251 group was intraperitoneally injected with 1.5 mg/kg cannabinoid type I receptor(CBR1)blocker AM251 before daily gavage on the basis of prevention group.The body weight of the rats in each group was recorded every 7 days,and their mechanical foot withdrawal threshold(MWT)was tested by von fery filaments,all the rats were observed for a total of 28 days.After 28 days of experimental observation,the expression levels of CBR1,CBR2,glial fibrillary acidic protein(GFAP),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)mRNA in the spinal cord tissue of each group was detected by RT-PCR.Results On the 7th,14th,21th,and 28th day of the experiment,there was no significant difference in the increase of body weight between every group(P>0.05).The MWT on the 7th,14th,21th,and 28th day of experiment in the model group were significantly lower than those of the control group at the same period(P<0.05);the MWT of the prevention group and the AM251 group were significantly higher than those of the model groups on the 14th,21th,and 28th day of experiment(P<0.05),but there was no significant difference between the AM630 group and the model group,and between the prevention group and the AM251 group(P>0.05).The expression levels of CBR2,CBR1 and GFAP mRNA in the model group were not significantly different from those in the control group(P>0.05),and the expression levels of IL-1βand TNF-αmRNA were significantly higher than those in the control group(P<0.05);the expression levels of CBR2 mRNA in the prevention group and AM251 group were significantly higher than those in the model group(P<0.05),and the expression levels of IL-1βand TNF-αmRNA were significantly lower than those in the model group(P<0.05).there was no significant difference in mRNA expression level of each related protein between the AM630 group and the model group,and between the prevention group and the AM251 group(P>0.05).Conclusion Buyang Huanwu Decoction can prevent paclitaxel-induced peripheral neuralgia.The mechanism may be related to its activation of spinal cord CBR2 and further inhibition of the expression of inflammatory cytokines such as IL-1βand TNF-αin the spinal cord.