Ⅰ组代谢型谷氨酸受体在帕金森病大鼠模型中的表达变化  

Changes in expression of groupⅠmGluRs in a 6-OHDA model of Parkinson’s disease

作　　者：杨叔媛 宋璐[1] 吴娜[1] 万赢[1] 干静[1] 刘振国[1] YANG Shuyuan;SONG Lu;WU Na;WAN Ying;GAN Jing;LIU Zhenguo(Department of Neurology,Xinhua Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院神经内科

出　　处：《中国神经免疫学和神经病学杂志》2021年第6期469-474,共6页Chinese Journal of Neuroimmunology and Neurology

基　　金：国家重点研发计划“重大慢性非传染性疾病防控研究”重点专项(2017YFC1310300);国家自然科学基金项目(81974173,81703852);上海交通大学医学院附属新华医院院基金(18YJ13)。

摘　　要：目的通过研究Ⅰ组代谢型谷氨酸受体(mGluRs)mGluR1及mGluR5在帕金森病(PD)大鼠纹状体神经元细胞膜蛋白和总蛋白的表达变化,探讨Ⅰ组mGluRs在纹状体神经元细胞膜/细胞内分布改变是否参与PD的发病机制。方法选取雄性SD大鼠20只,随机分为PD组〔以6-羟多巴(6-OHDA)单侧脑内注射法制备;n=10〕和Sham组(操作方法相同,以等量生理盐水代替6-OHDA;n=10)。采用Western blot方法检测两组大鼠纹状体损伤侧和非损伤侧mGluR1及mGluR5总蛋白和膜蛋白水平变化,以及其下游重要信号分子细胞外信号调节激酶1/2(ERK1/2)和c-Jun氨基末端激酶(JNK)磷酸化水平,比较两组损伤侧与非损伤侧上述各指标表达情况。结果Western blot结果显示Sham组非损伤侧、Sham组损伤侧、PD组非损伤测及PD组损伤侧mGluR1总蛋白水平差异无统计学意义(F=0.329,P=0.805),PD组损伤侧mGluR1膜蛋白表达较PD组非损伤侧、Sham组损伤侧和Sham组非损伤侧均明显增高(均P<0.05);PD组损伤侧mGluR5总蛋白水平和膜蛋白水平均较相应PD组非损伤侧、Sham组损伤侧及Sham组非损伤侧均明显增高(均P<0.05);与PD组非损伤侧、Sham组损伤侧和Sham组非损伤侧比较,PD组损伤侧ERK1/2磷酸化水平明显降低,JNK磷酸化水平明显升高(均P<0.05);上述指标在PD组非损伤侧、Sham组损伤侧和Sham组非损伤侧之间两两比较差异均无统计学意义(均P>0.05)。结论PD大鼠纹状体Ⅰ组mGluRs的变化以膜蛋白的表达异常增加为主,可能与其在细胞膜/细胞内分布的改变相关,并且改变可能影响下游ERK1/2和JNK磷酸化水平,推测纹状体神经元Ⅰ组mGluRs分布的变化可能与PD发病机制相关。Objective To explore whether the change of the striatal neuron membrane/intracellular distribution of groupⅠmetabotropic glutamate receptors(mGluRs)is involved in the pathogenesis of Parkinson’s disease(PD),by studying the alternation of mGluRs membrane-protein and total protein expression in the striatum of PD rat model.Methods Twenty male SD rats were randomly divided into a PD group(prepared by unilateral intracerebral injection of 6-OHDA;n=10)and a sham group(prepared by the same method,with the same amount of saline instead of 6-OHDA;n=10).Western blot method was used to detect changes of the total protein and membrane protein expression of mGluR1 and mGluR5,in the lesion and non-lesion sides of the two groups,as well as the phosphorylation levels of extracellular signal-regulated kinases 1/2(ERK1/2)and c-Jun N-terminal kinase(JNK)which are important signal molecules downstream of mGluR1 and mGluR5.The expressions of these proteins in lesion and non-lesion sides were compared between the two groups.Results The data showed that the total expression of mGluR1 in non-lesion sides of the sham group,lesion side of the sham group,non-lesion side of the PD group and the lesion side of the PD group were not significantly different(F=0.329,P=0.805).The membrane-expression of mGluR1 in the lesion side of the PD group was significantly higher than the non-lesion side of the PD group,lesion side of the sham group,and non-lesion side of the sham group(P<0.05,respectively).Both total expression and membrane-expression of mGluR5 in the lesion side of the PD group were significantly higher than those in the non-lesion side,lesion side of the sham group,and non-lesion side of the sham group(P<0.05,respectively).Compared with unlesion side of the PD group,lesion side of the sham group,and non-lesion side of the sham group,the phosphorylation level of ERK1/2 in the lesion side of the PD group was significantly decreased,while the phosphorylation level of JNK was significantly increased(P<0.05,respectively).Conclusions The

关 键 词：Ⅰ组代谢型谷氨酸受体 6-羟多巴 帕金森病 MGLUR1 MGLUR5 

分 类 号：R742.5[医药卫生—神经病学与精神病学]