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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    

Exploring the protective mechanism of Huangqi Baihe Granule(黄芪百合颗粒)against lung injury in high-altitude hypoxic rats based on the Bax/Bcl-2/Caspase-3 pathway

文献类型:期刊文献

中文题名: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

英文题名:Exploring the protective mechanism of Huangqi Baihe Granule(黄芪百合颗粒)against lung injury in high-altitude hypoxic rats based on the Bax/Bcl-2/Caspase-3 pathway

作者:黄勇[1,2,4];霍佳伟[1,2];苏韫[1,2];潘明月[1,2];张能贤[1,2];曹旺杰[1,2];龚红霞[1,2];刘永琦[1,2];陈红纲[3]

第一作者:黄勇

机构:[1]甘肃中医药大学基础医学院,甘肃兰州730000;[2]甘肃省高校重大疾病分子医学与中医药防治研究省级重点实验室,甘肃兰州730000;[3]甘肃省人民医院,甘肃兰州730000;[4]甘肃省中医药研究中心,甘肃兰州730000

第一机构:甘肃中医药大学基础医学院(敦煌医学研究所)

年份:2026

卷号:37

期号:4

起止页码:608

中文期刊名:时珍国医国药

外文期刊名:JOURNAL OF LI-SHIZHEN TRADITIONAL CHINESE MEDICINE

收录:;北大核心:【北大核心2023】;

基金:国家自然科学基金地区基金(82060833);甘肃省自然科学基金(23JRRA1212);甘肃省中医药研究中心开放课题(zyzx-2024-zx12);甘肃省中医药管理局项目(GZKP-2021-32)。

语种:中文

中文关键词:黄芪百合颗粒;高原低氧;急性肺损伤;细胞凋亡;Bax/Bcl-2/Caspase-3信号通路;润肺益肾;滋阴补气

外文关键词:Huangqi Baihe Granules(黄芪百合颗粒);High-altitude hypoxia;Acute lung injury;Apoptosis;Bax/Bcl-2/Caspase-3 signaling pathway;Moistening lung and tonifying kidney;Nourishing yin and replenishing qi

摘要:目的通过分子对接技术结合动物实验研究黄芪百合颗粒通过Bax/Bcl-2/Caspase-3信号通路对高原低氧大鼠模型急性肺损伤中肺组织细胞凋亡的影响。方法通过TCMSP数据库筛选黄芪百合颗粒活性成分,用CB-Dock2软件验证其与Bax、Bcl-2、Caspase-3、Caspase-9的结合能力。将大鼠分为空白组、模型组、阳性药组(地塞米松,进舱前3天腹腔注射,5 mg·kg^(-1)·d^(-1))及黄芪百合颗粒低(1.105 g·kg^(-1)·d^(-1))、中(2.21 g·kg^(-1)·d^(-1))、高(4.42 g·kg^(-1)·d^(-1))剂量组,后者均1次/d,给药14 d。第15天除空白组外,其余组大鼠以高原低氧环境造模,置动物低压模拟舱造模7 d,后处死取肺组织,行HE染色、TUNEL染色,WB和qRT-PCR测定相关蛋白及mRNA表达。结果分子对接显示,黄芪百合颗粒代表性小分子与目标蛋白Vina分数均<-6.0。动物实验中,模型组肺组织肺泡壁增厚、充血、炎性浸润,细胞凋亡增加(P<0.01),Caspase-3、Caspase-9、Bax表达升高(P<0.01),Bcl-2降低(P<0.01,P<0.05);阳性药组及黄芪百合颗粒各组上述病理损伤减轻,细胞凋亡减少(P<0.01),相关蛋白及mRNA表达改善(P<0.01,P<0.05),其中低剂量组仅Caspase-3、Caspase-9、Bax蛋白及Caspase-3 mRNA表达显著降低(P<0.01,P<0.05)。结论黄芪百合颗粒通过调节Bax/Bcl-2/Caspase-3信号通路抑制细胞凋亡,对高原低氧引起的急性肺损伤具有明显保护作用,为高原环境下肺损伤的防治提供了潜在干预策略。
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 experiments,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 strategy for preventing and treating lung injury under high-altitude conditions.

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