苁蓉舒痉颗粒减轻线粒体损伤抑制帕金森病神经炎症OA

Objective To investigate the mechanism by which Congrong Shujing Granules(CSG)alleviate neuroinflammation in Parkinson's disease(PD)by regulating dynamin-related protein 1(Drp1)-mediated mitochondrial damage and the NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome pathway.Methods Forty-eight SPF-grade healthy male C57BL/6J mice were randomly divided into the control group,model group,CSG group and Madopar group using a random number table,with 12 mice in each group.A PD mouse model was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).The mice were treated with CSG or Madopar for 4 weeks.Motor function,dopaminergic neuronal integrity,mitochondrial function,and inflammatory responses were systematically evaluated using behavioral tests,immunohistochemistry,immunofluorescence,transmission electron microscopy,flow cytometry,Western Blot,and ELISA.Results Compared with the control group,the model group exhibited significant motor dysfunction,decreased tyrosine hydroxylase(TH)expression in the substantia nigra,increased ionized calcium-binding adaptor molecule 1(IBA1)expression,marked mitochondrial structural damage,and elevated reactive oxygen species(ROS)levels.In addition,the expression of phosphoglycerate mutase family member 5(PGAM5)and Drp1 were upregulated,the p-Ser637 Drp1/Drp1 ratio was decreased,and the levels of NLRP3 inflammasome-related proteins[including apoptosis-associated speck-like protein containing a CARD(ASC)and Caspase-1],as well as inflammatory cytokines(IL-1 β,IL-6,TNF-α),and iNOS were increased(P＜0.05).Compared with the model group,CSG improved motor function,increased TH expression,reduced IBA1 expression,attenuated mitochondrial damage and ROS accumulation,downregulated PGAM5 and Drp1 expression,increased the p-Ser637 Drp1/Drp1 ratio,and decreased NLRP3 inflammasome-related proteins and inflammatory cytokines levels(P＜0.05).Conclusion CSG exerts anti-neuroinflammatory and dopaminergic neuroprotective effects in PD by regulating Drp1-mediated mitochondrial dynamics,reducing ROS generation,and subsequently inhibiting NLRP3 inflammasome activation.