人参皂苷Rg1介导HSPA8自噬途径改善帕金森小鼠黑质神经元损伤  

Gi nsenoside Rg1 mediates HSPA8 autophagy pathway to improve neuronal damage in substantia nigra of Parkinson mice

作　　者：陈金友 高越[1] Chen Jinyou

机构地区：[1]浙江大学医学院附属杭州市第一人民医院,310006

出　　处：《浙江临床医学》2023年第7期964-967,共4页Zhejiang Clinical Medical Journal

基　　金：浙江省医药卫生科技计划项目(2020KY705);杭州市医学重点学科建设资助项目(OO20200055);杭州市卫生科技计划项目(A20200691)。

摘　　要：目的探讨人参皂苷Rg1对帕金森病(PD)小鼠的神经保护作用及对热休克蛋白A8(HSPA8)的影响。方法48只C57BL/6J小鼠随机分为对照组(NC组)、PD组、Rg1-1组(1 mg/kg Rg1)、Rg1-5组(5 mg/kg Rg1)、Rg1-10组(10 mg/kg Rg1)、Rg1-20组(20 mg/kg Rg1)、Rg1-40组(40 mg/kg Rg1)、Rg1-40+VER-155008组(40 mg/kg Rg1+HSPA8抑制剂),每组各6只。除NC组外,其他小鼠腹腔注射1-甲基-4苯基-1,2,3,6-四氢吡啶(MPTP)制备PD模型,随后药物干预10 d,干预同时Rg1-40+VER-155008组小鼠腹腔VER-155008。行为学实验评价小鼠行为运动能力,Nissl染色和Tunel染色检测黑质神经元细胞的尼氏小体数量生成和凋亡情况,免疫组化检测小鼠黑质内α-突触核蛋白(α-Synuclein)、HSPA8表达,免疫荧光测定小鼠黑质内络氨酸氢化酶(TH)、自噬蛋白LC3、p62表达,Western blot检测小鼠黑质内α-Synuclein、HSPA8、TH、LC3-I/II、p62、B淋巴细胞瘤-2(Bcl-2)、半胱氨酸肽酶3(Caspase 3)、BCL2关联X蛋白(BAX)表达量。结果Rg1干预后,PD小鼠行为运动能力提高,神经细胞的尼氏小体数量增加、凋亡减少,黑质内HSPA8、TH、LC3-II/LC3-I、Bcl-2蛋白表达增加,α-Synuclein、p62、caspase-3、Bax蛋白表达降低,以Rg1-40组效果最为显著(P<0.05)。而与Rg1-40组比较,Rg1-40+VER-155008组小鼠的行为运动改善程度降低,神经元细胞尼氏小图数量减少、凋亡增加,TH、LC3-II/LC3-I、Bcl-2蛋白表达减少,而α-Synuclein、p62、caspase-3、Bax蛋白表达增加(P<0.05)。结论Rg1可介导HSPA8增强神经元细胞自噬活性从而对PD小鼠具有神经保护作用。Objective To study the neuroprotective effect of ginsenoside Rg1 on Parkinson's disease(PD)mice and its impact on hot shock protein A8(HSPA8).Methods Forty-eight C57BL/6J mice were divided into the control group(NC group),the PD group,the Rg1-1 group(1 mg/kg Rg1),the Rg1-5 group(5 mg/kg Rg1),the Rg1-10 group(10 mg/kg Rg1),the Rg1-20 group(20 mg/kg Rg1),the Rg1-40 group(40 mg/kg Rg1),and the Rg1-40+VER-155008 group(40 mg/kg Rg1+HSPA8 inhibitor),with six in each group.Except from the mice of the NC group,the other mice were intraperitoneally injected with MPTP to establish PD model,then were received Rg1 intervention for 10 days.The Rg1-40+VER-155008 group mice were intraperitoneally injected with VER-155008 at same time.The behavioral experiments were used to evaluate the behavior and exercise abilities of mice,the Nissl and tunel staining were used to determine the number of nissl body and apoptosis of neurons in substantia nigra,the immunohistochemistry was used to detect the expression ofα-Synuclein and HSPA8 in substantia nigra,the immunofluorescence was used to detect the expression of p62,TH and LC3 in substantia nigra,and the Western blot was used to detect the protein expression ofα-Synuclein,HSPA8,TH,LC3-I/II,p62,B-cell lymphoma-2(Bcl-2),Caspase-3,Bcl-2 associated X(Bax)in substantia nigra.Results After the Rg1 intervention,the behavior and exercise abilities of mice were improved,number of Nissl body of neurons were increased,neurons apoptosis were reduced,the protein expression of HSPA8,TH,LC3-II/LC3-I,Bcl-2 were increased,the protein expression ofα-Synuclein,p62,caspase-3,Bax were reduced,with statistical significance(P<0.05).Compared to the Rg1-40 group,the improvement of the behavior and exercise abilities in Rg1-40+VER-155008 group mice were decreased,the number of Nissl body of neurons were reduced,the neurons apoptosis were increased,the protein expression of TH,LC3-II/LC3-I,Bcl-2 were reduced,while the protein expression ofα-Synuclein,p62,caspase-3,Bax were increased,with statistical signific

关 键 词：人参皂苷RG1 帕金森 HSPA8 自噬 LC3-II/LC3-I P62 凋亡 

分 类 号：R285.5[医药卫生—中药学]