“抗帕颗粒”通过PINK1/Parkin信号通路对帕金森小鼠结肠ICC线粒体自噬的影响  

dMice with Parkinson's disease exhibit an effect of anti-Parkin disease granules on colon ICC mitochondrial autophagy via the PINK1/Parkin signaling pathway

作　　者：王思思[1] 王永兵[2] 刘慧琴[1] 杨娟[1] 颜国正[3] 赵晓晖[1] Wang Sisi;Wang Yongbing;Liu Huiqin;Yang Juan;Yan Guozheng;Zhao Xiaohui(Department of Neurology,Shanghai Pudong New Area People's Hospital,Shanghai 201200,China)

机构地区：[1]上海市浦东新区人民医院神经内科,上海201200 [2]上海市浦东新区人民医院普外科,上海201200 [3]上海交通大学

出　　处：《脑与神经疾病杂志》2024年第6期392-396,F0003,共6页Journal of Brain and Nervous Diseases

基　　金：上海市浦东新区卫生系统重点亚专科建设资助项目(PWZy2020-01);上海市浦东新区卫生系统重点学科建设资助项目(PWZxk2022-23);国家自然科学基金面上项目(81971767)。

摘　　要：目的 探讨“抗帕颗粒”通过PINK1/Parkin信号通路对帕金森(PD)小鼠结肠Cajal间质细胞(ICC)线粒体自噬的影响。方法 MPTP腹腔注射技术用于制作PD小鼠模型,将其随机分为A组(空白对照组)、B组(PD对照组)和C组(PD “抗帕颗粒”组),每组10只。A组和B组接受生理盐水灌胃(1mL·d^(-1)),C组“抗帕颗粒”(40mg·kg^(-1)·d^(-1))的灌胃治疗。4个月后每组中随机取5只小鼠结肠组织被用于免疫组化检测,每组余下5只小鼠结肠壁组织被用于提取蛋白Western blotting法检测,检测项目为PINK1、Parkin的表达;透射电子显微镜观测结肠壁ICC细胞自噬情况。结果(1)经过免疫组化检测,B组和C组的PINK1和Parkin表达水平较A组显著上升(P <0.01);而C组的PINK1和Parkin表达水平较B组则显著下降(P<0.01);(2)经过Western blot检测,与A组相比,B组和C组的PINK1和Parkin表达水平均显著提高(P<0.01);最后,经过与B组对比分析,发现C组PINK1的表达水平没有明显变化,而Parkin的表达水平却有所下降(P<0.05);(3)透射电子显微镜观察发现,PD模型小鼠结肠ICC中存在自噬囊泡,“抗帕颗粒”干预后,这种囊泡的数量明显减少。结论 “抗帕颗粒”通过抑制PD小鼠肠道ICC过度自噬,保护细胞结构;PINK1/Parkin途径是实现这种神经保护作用的通路。Objective The aim of this study was to explore the influence of anti-Parkinson's disease(PD)granules on mitochondrial autophagy in Cajal interstitial cells(ICC)of colon of PD mice via the PINK1/Parkin signaling pathway.Methods PD mice models were generated by intraperitoneal injection of MPTP and randomly divided into blank control group(group A),PD control group(group B),and anti-PD granules group(group C),with 10 mice in each group.Group A and B were administered 1ml of saline intragastric,while Group C was given 40mg of anti-PD granules intragastric(d^(-1)).Randomly selecting 5 colon tissues from each group after 4 months,immunohistochemical detection was conducted.Western blotting was then used to extract protein from the intestinal wall tissues of the remaining 5 mice in each group.Detection items included the expression of PINK1 and Parkin.Transmission electron microscopy was then used to observe the autophagy of ICC cells in the colon wall.Results①Immunohistochemical results indicated a significant increase in the expression of PINK1 and Parkin in groups B and C,compared to group A(P<0.01);conversely,group C's expression levels of PINK1 and Parkin were significantly decreased(P<0.01);②The Western blot revealed that,in comparison to group A,the expression of PINK 1 and Parkin was significantly augmented in groups B and C(P<0.01);however,compared with group B,PINK1 expression in group C remained unchanged,and Parkin expression was reduced(P<0.05);③Transmission electron microscopy showed that autophagy vesicles appeared in the colon ICC of PD model mice,and the autophagy vesicles of PD model mice were reduced after the intervention of anti-PD granules.Conclusion Anti-PD granules can protect the cell structure of intestinal ICC by inhibiting excessive autophagy in PD mice.The PINK1/Parkin pathway is the pathway that enables this neuroprotective effect.

关 键 词：帕金森病 “抗帕颗粒” 结肠ICC细胞 自噬 PINK1/Parkin 

分 类 号：R742.5[医药卫生—神经病学与精神病学]