清肺解毒化痰方抑制PINK1/Parkin通路介导的线粒体自噬治疗重症肺炎大鼠的机制研究OA

Objective To elucidate the mechanism by which Qingfei Jiedu Huatan Formula(清肺解毒化痰方,QJHF)treats severe pneumonia in rats through inhibition of PINK1/Parkin-mediated mitophagy.Methods SD rats were randomly divided into four groups(n=20 each):control,model,QJHF,and Moxifloxacin(MOX).A severe pneumonia model was established using Klebsiella pneu-moniae.Lung tissues were collected on days 4 and 7 post-treatment for analysis.Hematoxylin-eosin(HE)staining was used to evaluate pathological changes,immunohistochemistry(IHC)to detect IL-6 and MCP-1 expressions,immunofluorescence to assess mitophagy levels(via LC3B and HSP60 co-localization),and RT-qPCR/Western blot(WB)to measure PINK1,Parkin,and VDAC1 mRNA/pro-tein expression.Results Compared with the control group,the model group exhibited alveolar wall rupture and fusion,inflammatory cell infiltration,significantly elevated lung injury scores(LIS)(P<0.01),upregulated IL-6 and MCP-1 expression(P<0.01),enhanced LC3B fluorescence,increased HSP60-LC3B co-localization(P<0.01),and elevated PINK1,Parkin,and VDAC1 mRNA/protein levels(P<0.01)on days 4 and 7.Compared with the model group,both QJHF and MOX groups showed reduced inflammatory cell infil-tration,decreased LIS(P<0.01),downregulated IL-6 and MCP-1(P<0.01),weakened LC3B fluorescence,reduced HSP60-LC3B co-localization(P<0.01),and suppressed PINK1,Parkin,and VDAC1 expression(P<0.01 or P<0.05).Therapeutic effects were time-dependent(P<0.01).Conclusion QJHF alleviates pulmonary pathological damage and preserves the lung function in severe pneu-monia rats by inhibiting excessive mitophagy via modulating the PINK1/Parkin pathway.