黄芪提取物对帕金森病小鼠黑质区白介素-17通路的影响  

Effect of Astragalus extract on IL-17 signaling pathway in substantia nigra of Parkinson's disease mice

作　　者：关勇宇 张广润 李海龙[1] 邵菲菲[2] GUAN Yongyu;ZHANG Guangrun;LI Hailong;SHAO Feifei(Gansu University of Traditional Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]甘肃中医药大学,甘肃兰州730000 [2]甘肃省人民医院,甘肃兰州730000

出　　处：《陕西中医》2024年第4期468-472,共5页Shaanxi Journal of Traditional Chinese Medicine

基　　金：甘肃省青年科技基金资助项目(21JR7RA652)。

摘　　要：目的:探究黄芪提取物干预白介素-17(IL-17)信号通路治疗帕金森病(PD)作用机制。方法:将30只雄性C57BL/6小鼠均分为五组。除对照组之外均采用MPTP诱导PD模型,建模成功后,低、中、高浓度黄芪组分别以50、100、200 mg/kg黄芪提取物持续灌胃14 d,模型组和对照组采用等量0.9%氯化钠溶液灌胃。灌胃后结束后采用转棍实验和爬杆实验评估各组小鼠行为表现。免疫组化法测定各组脑黑质致密区(SNpc)酪氨酸羟化酶(TH)和Th17细胞数目;Western blot测定纹状体区IL-17、抗肿瘤坏死因子受体相关因子6(TRAF6)、核因子-κB(NF-κB)、白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、环氧合酶-2(COX-2)蛋白相对表达量。结果:与对照组比较,模型组和各浓度黄芪组小鼠转棍掉落潜伏期明显缩短,爬杆实验头向下时间(T1)、由杆顶爬至杆底所用时间(T-LA)明显延长,SNpc区TH表达水平下降,Th17细胞数目增多,纹状体区IL-17、TRAF-6、NF-κB、IL-1β、IL-6、TNF-α、COX-2蛋白相对表达水平明显升高(均P<0.05)。与模型组比较,各浓度黄芪组小鼠转棍掉落潜伏期明显延长,爬杆实验T1和T-LA明显缩短,SNpc区TH表达水平升高,Th17细胞数目减少,纹状体区IL-17、TRAF-6、NF-κB、IL-1β、IL-6、TNF-α、COX-2蛋白相对表达水平明显下降(均P<0.05),且与黄芪提取物浓度呈正相关。结论:黄芪提取物能有效改善PD模型小鼠转棍和爬杆活动能力,保护SNpc区TH阳性神经元,其机制可能与抑制IL-17/TRAF-6/NF-κB信号通路,减少多巴胺神经元炎症性损伤凋亡有关。Objective:To explore the therapeutic effect of astragalus extract on Parkinson's disease(PD) by intervening the interleukin-17(IL-17) signaling pathway.Methods:30 male C57BL/6 mice were divided into 5 groups.Except the control group,MPTP was used to induce PD model.After successful modeling,the low,medium and high concentration groups were given 50,100 and 200 mg/kg Astragalus extract for 14 days,respectively.And model group and control group were given the same amount of normal saline.After the end of intragastric administration,the behavior of each group of mice was evaluated by rotating stick test and climbing pole test.The numbers of tyrosine hydroxylase(TH) and Th17 cells in the dense region of substantia nigra(SNpc) were determined by immunohistochemistry.Western blot assay was used to determine the protein phases of IL-17,anti-tumor necrosis factor receptor-associated factor 6(TRAF6),nuclear factor-κB(NF-κB),interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and anti-cyclooxygenase-2(COX-2) in the striate body region on the amount of expression.Results:Compared with the control group,the incubation period of mice in model group and Astragalus group was significantly shortened,the times of T1 and T-LA were significantly prolonged,TH expression level in SNpc region decreased,and Th17 cell number increased,the relative expression levels of IL-17,TRAF-6,NF-κB,IL-1β,IL-6,TNF-α and COX-2 proteins in striatum were significantly increased(all P<0.05).Compared with model group,the incubation period of mice in Astragalus group was significantly prolonged,the times of T1 and T-LA were significantly shortened,TH expression level in SNpc region was increased,and the number of Th17 cells was decreased,and the relative expression levels of IL-17,TRAF-6,NF-κB,IL-1β,IL-6,TNF-α and COX-2 proteins in striatum were significantly decreased(all P<0.05).The levels of all observation indexes in Astragalus group were significantly correlated with the concentration of Astragalus extract.Conclusion:

关 键 词：帕金森病 黄芪提取物 黑质 信号通路 白细胞介素-17 小鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]