脑蛋白水解物-Ⅰ对帕金森病小鼠肠道菌群的调节作用  

Effect of cerebrotein hydrolysate-Ⅰon intestinal microflora regulation of mice with Parkinson’s disease

作　　者：阎锟 武筱林 刘英娟 葛科立 任雷鸣[2] 李红云[3] YAN Kun;WU Xiao-lin;LIU Ying-juan;GE Ke-li;REN Lei-ming;LI Hong-yun(Institute of Integrative Medicine,Qingdao University Medical College,Qingdao 266021,China;Institute of Chinese Integrative Medicine,Hebei Medical University,Shijiazhuang 050017,China;Department of Neurology,the Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学医学部中西医结合中心,青岛266021 [2]河北医科大学中西医结合研究所,石家庄050017 [3]青岛大学附属医院神经内科,青岛266003

出　　处：《解剖学报》2023年第5期497-504,共8页Acta Anatomica Sinica

基　　金：国家自然科学基金(81973501);河北智同科学基金(2018ZD1901)。

摘　　要：目的探讨脑蛋白水解物-Ⅰ(CH-Ⅰ)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)小鼠神经保护的作用和机制。方法成年健康雄性C57BL/6小鼠36只,按照随机对照原则,将小鼠分为对照组(Ctrl),模型组(MPTP)和CH-Ⅰ组,应用MPTP诱导小鼠PD模型。通过腹腔注射CH-Ⅰ干预治疗,爬杆实验检测小鼠的行为功能,免疫组织化学检测酪氨酸羟化酶(TH)表达水平,基因测序和生物信息学分析法检测肠道细菌群落的组成和多样性。结果行为学结果显示,模型制作后与Ctrl组相比,MPTP可诱导PD小鼠出现行为学缺陷(P<0.05),经CH-Ⅰ处理后与MPTP组相比,PD小鼠的行为学缺陷有所改善(P<0.05)。免疫组织化学结果显示,MPTP使多巴胺合成中的限速酶TH表达水平降低,CH-Ⅰ处理后TH表达水平升高。微生物多样性结果显示,MPTP处理后小鼠肠道微生物多样性降低(P<0.05);在“门”水平上,ε-变形菌门及脱硫杆菌门的数量骤降,疣微菌门菌群的数量显著增加;在“科”水平上,弧菌科、毛螺菌科、螺旋杆菌科及理研菌科菌群的数量减少,而艾克曼菌科菌群与丹毒丝菌科的数量增加,提示肠道微生物菌群原有稳态被破坏;经CH-Ⅰ处理后各菌群数量趋于正常,其减少了致病性微生物群的丰度并增加了有益细菌的相对丰度。结论CH-Ⅰ可通过降低病原微生物的丰度和增加有益细菌的相对丰度,改善肠道微生物的组成,改善PD小鼠的行为功能。Objective To investigate the neuroprotective effect and mechanism of cerebrotein hydrolysate-Ⅰ(CH-Ⅰ)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)induced Parkinson’s disease(PD)mice.Methods Totally 36 healthy male C57BL/6 mice were randomly divided into control group(Ctrl),model group(MPTP)and CH-Ⅰgroup.MPTP was used to induce PD model in mice,and CH-Ⅰwas injected intraperitoneally for intervention.The behavioral function of mice was detected by pole test,the expression of tyrosine hydroxylase(TH)was detected by immunohistochemistry,and the composition and diversity of intestinal microflora were detected by gene sequencing and bioinformatics analysis.Results Compared with the control group,MPTP induced behavioral deficits in PD mice after modeling(P<0.05),after CH-Ⅰtreatment,the behavioral defects of PD mice were improved compared with MPTP group(P<0.05).Immunohistochemical result showed that MPTP decreased the expression of the rate-limiting enzyme TH in dopamine synthesis,and increased the expression of TH after CH-Ⅰtreatment.The result of microbial diversity showed that the intestinal microflora diversity of mice decreased after MPTP treatment(P<0.05).At the“phylum”level,the number of Epsilonbacteraeota and Deferribacteres decreased sharply,while the number of Verrucomicrobia increased significantly.At the level of“family”,the number of Desulfovibrionaceae,Lachnospiraceae,Helicobacteraceae and Rikenellaceae decreased,while the number of Akkermansiaceae and Erysipelotrichaceae increased,suggesting that the original homeostasis of intestinal microflora was destroyed.After CH-Ⅰtreatment,the number of intestinal microflora tended to be normal,which reduced the abundance of pathogenic microbiota and increased the relative abundance of beneficial bacteria.Conclusion CH-Ⅰcan improve the composition of intestinal microflora and the behavioral function of PD mice by decreasing the abundance of pathogenic microbiota and increasing the relative abundance of beneficial bacteria.

关 键 词：脑蛋白水解物-Ⅰ 帕金森病 肠道菌群 酪氨酸羟化酶 免疫组织化学 小鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]