桃红四物汤对紫杉醇所致大鼠外周神经损伤的保护作用及其机制  

Protective effect and potential mechanism of Taohong Siwu decoction on peripheral nerve injury of paclitaxel

作　　者：韩滨[1] 郝晨伟[1] 董敏[1] 李正翔[1] Han Bin;Hao Chen-Wei;Dong Min;Li Zheng-Xiang(Department of Pharmacy,General Hospital of Tianjin Medical University,Tianjin 300052,China)

机构地区：[1]天津医科大学总医院药剂科,天津300052

出　　处：《解放军医学杂志》2023年第5期570-576,共7页Medical Journal of Chinese People's Liberation Army

基　　金：天津市卫生健康委员会天津市中医药管理局中医中西医结合科研课题(2019135)。

摘　　要：目的 观察桃红四物汤(THD)对紫杉醇所致大鼠外周神经损伤的作用并探讨其相关机制。方法 将24只雌性SD大鼠随机分为4组(对照组、模型组、THD低剂量组、THD高剂量组),每组6只。对照组以外的3组大鼠分别在第1、3、5、7天腹腔注入紫杉醇(8 mg/kg),诱导外周神经损伤模型,大鼠机械刺激撤足阈值<4 g为造模成功;THD低、高剂量组在造模同时灌胃给予相应浓度(1 g/ml、2 g/ml)的桃红四物汤(10 ml/kg),2次/d,连续4周。给药结束后检测各组大鼠对机械、冷、热刺激的敏感度,坐骨神经组织病理学改变,坐骨神经部位炎性因子白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、抗氧化因子还原型谷胱甘肽(GSH)及脂质过氧化因子硫代巴比妥酸反应物(TBARS)的水平,并检测坐骨神经部位髓鞘碎片及自噬相关蛋白微管相关蛋白1轻链3-I(LC3-I)、LC3-Ⅱ和Beclin1蛋白的表达水平。结果 与对照组比较,模型组大鼠的冷、热刺激敏感度和机械痛觉阈值均降低(P<0.05);坐骨神经病理结构显著破坏,且存在炎性浸润,髓鞘碎片增加(P<0.05);炎性因子IL-6、TNF-α和TRABS水平升高(P<0.05),GSH水平下降(P<0.05);自噬相关蛋白LC3-I、LC3-Ⅱ和Beclin1表达水平降低(P<0.05)。与模型组比较,THD低剂量组和高剂量组大鼠的冷、热刺激敏感度和机械痛觉阈值均增高(P<0.05);坐骨神经病理结构改善,仍存在炎性浸润,髓鞘碎片减少(P<0.05);炎性因子IL-6、TNF-α和TRABS水平降低(P<0.05),GSH水平增高(P<0.05);LC3-I、LC3-Ⅱ和Beclin1表达水平增高(P<0.05)。与THD低剂量组比较,THD高剂量组冷、热刺激敏感度和机械痛觉阈值均增高(P<0.05),坐骨神经髓鞘碎片减少(P<0.05),LC3-I、LC3-Ⅱ和Beclin1表达水平增高(P<0.05)。结论 THD可缓解紫杉醇造成的大鼠外周神经损伤,其机制可能与降低炎性反应、诱导自噬清除损伤碎片有关。Objective To investigate the effect and potential mechanism of Taohong Siwu decoction(THD)on paclitaxelinduced peripheral nerve injury in rat.Methods Twenty-four female SD rats were randomly divided into control group,model group,THD low-dose group and THD high-dos group(6 each).Rats in control group were given saline of the same volume,while paclitaxel(8 mg/kg)was slowly injected intraperitoneally into rats in other three groups on the 1,3,5,and 7th day for 4 times.Rats with mechanical withdrawal threshold under 4 g indicated model success.The THD low-dose group and THD high-dose group was given 1 g/ml or 2 g/ml of THD 2 times/d,for 4 weeks.The threshold of mechanical stimulation,cold and hot stimulation to rats was detected after administration.The pathological morphology of sciatic nerve was observed by HE staining.The contents of inflammatory factor Interleukin-6(IL-6),Tumor Necrosis Factor-α(TNF-α),thiobarbituric acid reactive substances(TBARS)and L-Glutathione(GSH)in the sciatic nerve were measured with automatic biochemical analyzer.The relative contents of myelination pieces were determined by red oil O staining and expression level of autophagy associated proteins microtubule-associated protein 1 light chain3-I(LC3-I),LC3-Ⅱ,and Beclin1 were detected by Western blotting.Results Compared with control group,rats in model group showed lower threshold to mechanical stimulation and lower sensitivity to hot and cold stimulation(P<0.05),expression levels of IL-6,TNF-αand TRABS elevated(P<0.05),while GSH levels decreased(P<0.05).HE staining showed tissue injury,atrophy,inflammatory infiltration,and myelination pieces increased significantly and expression of autophagy associated protein LC3-I,LC3-Ⅱand Beclin1 reduced(P<0.05).The results of THD low-dose group and THD high-dose group showed that the response of rats to mechanical stimulation,hot and cold stimulation was obviously improved(P<0.05),levels of IL-6,TNF-αand TRABS significantly decreased(P<0.05),while level of antioxidant GSH significantly eleva

关 键 词：紫杉醇 外周神经损伤 桃红四物汤 自噬 

分 类 号：R730.5[医药卫生—肿瘤]