黄芪桂枝五物汤加减方对紫杉醇所致周围神经病变的保护作用研究  

Protective effect of modified decoction of five drugs including Astragalus Root and Cinnamon Twig on paclitaxel-induced peripheral neuropathy

作　　者：李尚朋 齐婧[2] 吴少锋[2] 王茂[2] 高杰红 黎平平 王奇[2] 代引海[2] LI Shangpeng;QI Jing;WU Shaofeng;WANG Mao;GAO Jiehong;LI Pingping;WANG Qi;DAI Yinhai(The Second Clinical Medical College of Shaanxi University of Chinese Medicine,Xianyang 712000,Shaanxi,China;The Second Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,Shaanxi,China)

机构地区：[1]陕西中医药大学第二临床医学院,陕西咸阳712000 [2]陕西中医药大学第二附属医院,陕西咸阳712000

出　　处：《现代中西医结合杂志》2025年第6期745-751,840,共8页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：陕西省中医药管理局科研项目(2021-GJ-LC012)。

摘　　要：目的探究黄芪桂枝五物汤加减方对紫杉醇所致周围神经病变(PIPN)大鼠的保护作用和可能作用机制。方法将70只雄性SD大鼠随机分为对照组、模型组、甲钴胺组、原方组、加减方组、原方+甲钴胺组、加减方+甲钴胺组,每组10只。除对照组外,其余组大鼠采用隔日腹腔注射紫杉醇的方法制备PIPN模型。同时自实验第1天开始,甲钴胺组给予1 mg/mL甲钴胺水溶液1 mL/kg灌胃,原方组给予2 g/mL黄芪桂枝五物汤10 mL/kg灌胃,加减方组给予2 g/mL黄芪桂枝五物汤加减方10 mL/kg灌胃,原方+甲钴胺组给予2 g/mL黄芪桂枝五物汤10 mL/kg和1 mg/mL甲钴胺溶液1 mL/kg灌胃,加减方+甲钴胺组给予2 g/mL黄芪桂枝五物汤加减方10 mL/kg和1 mg/mL甲钴胺水溶液1 mL/kg灌胃,对照组和模型组给予等体积的生理盐水灌胃,均1次/d,连续灌胃21 d。检测大鼠的机械痛阈值、热痛阈值,观察大鼠的体重变化,免疫荧光检测大鼠后足底皮肤组织中神经纤维损伤情况,Western blot法检测大鼠背根神经节内核因子E2相关因子2(Nrf2)、Kelch样ECH相关蛋白1(Keap1)、血红素氧合酶-1(HO-1)蛋白表达情况。结果与对照组比较,模型组大鼠实验第6,8,11,14,21天的机械痛阈值和实验第8,11,14,21天的热痛阈值均明显降低(P均<0.05),体重增长缓慢,后足底皮肤组织中PGP9.5阳性表达平均荧光强度明显降低(P<0.05),背根神经节中Nrf2、Keap1、HO-1蛋白相对表达量均明显升高(P均<0.05)。与模型组比较,各药物组大鼠实验第6,8,11,14,21天的机械痛阈值和实验第8,11,14,21天的热痛阈值均明显升高(P均<0.05),体重变化不明显,后足底皮肤组织中PGP9.5阳性表达平均荧光强度和背根神经节中Nrf2、HO-1蛋白相对表达量均明显升高(P均<0.05),背根神经节中Keap1蛋白相对表达量均明显降低(P均<0.05)。各药物组间比较,原方组、加减方组、原方+甲钴胺组、加减方+甲钴胺组大鼠实验第14天的机械痛�Objective It is to investigate the protective effects and mechanisms of modified decoction of five drugs including Astragalus Root and Cinnamon Twig on paclitaxel-induced peripheral neuropathy in rats.Methods Seventy male SD rats were randomly divided into control group,model group,mecobalamin group,original decoction group,modified decoction group,original decoction+mecobalamin group,modified decoction+mecobalamin group,with 10 rats in each group.The rats of all groups except for the control group were given paclitaxel by intraperitoneal injection every other day to establish models of PIPN.Meanwhile,since the 1st day of the experiment,the mecobalamin group was given 1 mg/mL mecobalamin aqueous solution 1 mL/kg by gavage,the original decoction group was given 2 g/mL decoction of five drugs including Astragalus Root and Cinnamon Twig 10 mL/kg by gavage,the modified decoction group was given 2 g/mL modified decoction of five drugs including Astragalus Root and Cinnamon Twig 10 mL/kg by gavage,the original decoction+mecobalamin group was given 2 g/mL decoction of five drugs including Astragalus Root and Cinnamon Twig 10 mL/kg combined with 1 mg/mL mecobalamin aqueous solution 1 mL/kg by gavage,the modified decoction+mecobalamin group was given 2 g/mL modified decoction of five drugs including Astragalus Root and Cinnamon Twig 10 mL/kg combined with 1 mg/mL mecobalamin aqueous solution 1 mL/kg by gavage,the control group and model group were given equal volumes of saline by gavage,all once daily,continuously treated for 21 days.The mechanical pain threshold and heat pain threshold of the rats were detected,the changes of their body weight were observed,the nerve fiber damage in skin tissue of hindfoot sole of the rats were detected by immunofluorescence,and the protein expressions of nuclear factor E_(2)-related factor 2(Nrf2),Kelch-like ECH-associated protein 1(Keap1)and heme oxygenase-1(HO-1)in dorsal root ganglion were detected by Western blot.Results Compared with the control group,the mechanical pain thresholds

关 键 词：紫杉醇所致周围神经病变 黄芪桂枝五物汤加减方 黄芪桂枝五物汤 热痛觉 氧化应激 

分 类 号：R-332[医药卫生]