基于Bax/Bcl-2/Caspase-3通路探讨黄芪百合颗粒对高原低氧大鼠肺损伤的保护机制OA

Objective To investigate the effect of Huangqi Baihe Granule(黄芪百合颗粒,HQBHG)on apoptosis in the lung tissue of a rat model with acute lung injury(ALI)induced by high-altitude hypoxia via the Bax/Bcl-2/Caspase-3 signaling pathway,using molecular docking technology combined with animal experiments.Methods Active components of HQBHG were screened from the TCMSP database.Their binding abilities to Bax,Bcl-2,Caspase-3,and Caspase-9 were verified using CB-Dock2 software.For animal experiments,a high-altitude hypoxic environment was modeled.Rats were divided into the blank group,model group,positive drug group(dexamethasone,intraperitoneal injection at 5 mg/kg/d for 3 days before cabin entry),and HQBHG low-(1.105 g/kg/d),medium-(2.21 g/kg/d),and high-dose(4.42 g/kg/d)groups.HQBHG groups were administered once daily for 14 days.On day 15,except for the blank group,all other groups were placed in an animal hypobaric chamber for 7 days to establish the model.Rats were then sacrificed,and the lung tissues were collected for hematoxylin-eosin(HE)staining,TUNEL staining,Western blot(WB),and quantitative real-time PCR(qRT-PCR)to determine the expression levels of related proteins and mRNAs.Results Molecular docking showed that the representative small molecules of HQBHG had Vina scores all below-6.0 with the target proteins.In animal experi-ments,the model group exhibited thickened alveolar walls,congestion,inflammatory infiltration,increased cell apoptosis(P<0.01),upregulated expression of Caspase-3,Caspase-9,and Bax(P<0.01),and downregulated Bcl-2(P<0.01,P<0.05)compared to the blank group.The positive drug group and all HQBHG treatment groups showed alleviated pathological injury,reduced cell apoptosis(P<0.01),and improved expression levels of related proteins and mRNAs(P<0.01,P<0.05)compared to the model group.Notably,in the HQBHG low-dose group,only the protein expression of Caspase-3,Caspase-9,and Bax,and the mRNA expression of Caspase-3 were significantly decreased(P<0.01,P<0.05).Conclusion HQBHG attenuate ALI induced by high-altitude hypoxia by inhibiting cell apoptosis,potentially through regulating the Bax/Bcl-2/Caspase-3 signaling pathway.This study provides a potential intervention strat-egy for preventing and treating lung injury under high-altitude conditions.