舒肌汤对左旋多巴诱发帕金森异动症大鼠神经保护作用的实验研究  

Study on Neuroprotection of Shuji Decoction(舒肌汤)on Levodopa-Induced Dyskinesia in Parkinson Rats

作　　者：刘超平 孙婷 鲍玺[2] LIU Chaoping;SUN Ting;BAO Xi(Third People’s Hospital of Huzhou,Huzhou,Zhejiang 313000;Hangzhou Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medicine University,Hangzhou,Zhejiang 310007)

机构地区：[1]浙江省湖州市第三人民医院,浙江湖州313000 [2]浙江中医药大学附属杭州市中医院,浙江杭州310007

出　　处：《中国中医药科技》2024年第3期396-401,共6页Chinese Journal of Traditional Medical Science and Technology

基　　金：浙江省中医药科技计划(2022ZA110)。

摘　　要：目的:探讨舒肌汤对左旋多巴(L-dopa)诱导帕金森(PD)异动症大鼠的神经保护作用及机制。方法:SD大鼠单侧注射6-羟基多巴胺(6-OHDA)建立制备PD模型,随后腹腔注射L-dopa、苄丝肼诱导异动症,随机分为模型组、低剂量舒肌汤组(10 g/kg)、中剂量舒肌汤组(20 g/kg)、高剂量舒肌汤组(40 g/kg),同时设立假手术组,每组6只,连续灌胃给药28 d,于治疗的第1、7、14、21、28天进行不自主运动(AIM)评分。治疗结束时,测定大鼠负重单肢跨步数;ELISA测定脑组织MDA、GSH、SOD、IL-1β、TNF-α、IL-6、IL-10水平,双荧光免疫染色测定CD11b^(+)Iba1^(+)小胶质细胞数量,Western blot测定络氨酸羟化酶(TH)蛋白表达。结果:与假手术组比较,模型组大鼠AIMs评分升高,单前肢跨步数减少,脑组织MDA、IL-1β、TNF-α、IL-6、IL-10水平升高,GSH、SOD水平降低,CD11b^(+)Iba1^(+)小胶质细胞数量增加,TH蛋白表达减少(均P<0.01)。与模型组比较,治疗第7天后各组大鼠AIMs评分降低;治疗结束时各组大鼠单前肢跨步数增加,脑组织MDA、IL-1β、TNF-α、IL-6、IL-10水平降低,CD11b^(+)Iba1^(+)小胶质细胞数量增加,TH蛋白表达增加(P<0.05);中、高剂量舒肌汤组大鼠GSH、SOD水平增加(P<0.05)。结论:舒肌汤对L-dopa诱导PD异动症大鼠的症状具有改善作用,其机制可能与抑制小胶质细胞激活下调各类炎性介质释放、减少氧化应激损伤、促进TH蛋白表达有关。Objective:To observe the neuroprotection effect a of Shuji Decoction(SJD)on dyskinesia induced by L-dopa in Parkinson’s(PD)rats and explore the mechanism.Methods:SD rats were used to establish PD model by by injecting 6-OHDA,then intraperitoneally injected with L-dopa and benzyl hydrazine to induce dyskinesia,and randomly divided into model group,low dose SJD group(10 g/kg),medium dose SJD group(20 g/kg),and high dose SJD group(40 g/kg),sham operation group(operations were replaced by normal saline)was set up at same time.Intragastric administration continuously for 28 d and evaluated the abnormal involuntary movement(AIM)after medication for1 d,7 d,14 d,21 d,28 d.Single leg steps of rats with weight bearing were determined;ELISA was used to detect the levels of brain MDA,GSH,SOD,IL-1β,TNF-α,IL-6,IL-10,dual fluorescent immunostaining was used to detect CD11b^(+)Iba1^(+)microglias,and Western blot was used to detect tyrosine hydroxylase(TH)protein expression.Results:Compared to sham group,AIM scores was higher in model group,and single leg steps were decreased,the levels of brain MDA,IL-1β,TNF-α,IL-6 and IL-10 were increased,while the content of GSH and SOD were decreased,CD11b^(+)Iba1^(+)microglia were increased,and the expression of TH protein decreased(all P<0.01).Compared to model group,AIMs scores of rats in each SJD group were decreased after 7 days of medication;single leg steps of rats in each SJD group were increased,levels of brain MDA,IL-1β,TNF-α,IL-6 and IL-10 were decreased,CD11b^(+)Iba1^(+)microglia were reduced,and expression of TH protein were increased(P<0.05);and levels of GSH,SOD of rats in medium,high SJD groups were increased(P<0.05).Conclusion:SJD can improve the symptoms of PD dyskinesia rats induced by L-dopa,and its mechanism may be related to inhibiting the activation of microglia to reduce the release of inflammatory mediators,reduce oxidation stress damage,and promoting the expression of TH protein.

关 键 词：帕金森异动症 左旋多巴 舒肌汤 小胶质细胞 炎性因子 氧化应激 TH蛋白 大鼠 

分 类 号：R285.5[医药卫生—中药学]