首页|芪蛭皱肺颗粒对慢性阻塞性肺疾病大鼠内质网应激的影响

芪蛭皱肺颗粒对慢性阻塞性肺疾病大鼠内质网应激的影响

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目的 观察芪蛭皱肺颗粒对慢性阻塞性肺疾病(COPD)大鼠内质网应激的影响,探讨其作用机制。方法 采用脂多糖气管滴注+烟熏诱导COPD大鼠模型,将60只Wistar大鼠用随机数字表法分为对照组、模型组、补肺活血胶囊组和芪蛭皱肺颗粒低、中、高剂量组,每组10只。造模第29日开始,给药组分别予相应药物灌胃,对照组和模型组灌胃生理盐水,连续28d。检测大鼠肺功能,HE染色观察肺组织形态,TUNEL染色检测肺组织细胞凋亡程度,RT-qPCR、Western blot检测肺组织内质网应激及凋亡相关因子基因和蛋白表达。结果 与对照组比较,模型组大鼠肺功能指标吸气峰流速(PIF)、呼气峰流速(PEF)、每分钟通气量(MV)显著降低,呼吸频率(F)显著升高(P<0。05);肺组织结构损伤明显,肺损伤评分及细胞凋亡率显著升高(P<0。05),肺组织葡萄糖调节蛋白78(GRP78)、蛋白激酶R样内质网激酶(PERK)、C/EBP同源蛋白(CHOP)、胱天蛋白酶(Caspase)-3、Caspase-9 mRNA表达升高(P<0。05),GRP78、p-PERK、转录激活因子4(ATF4)、CHOP、Caspase-3、Caspase-9蛋白表达升高(P<0。05)。与模型组比较,芪蛭皱肺颗粒中、高剂量组及补肺活血胶囊组大鼠PIF、PEF、MV显著升高,F显著降低(P<0。05),肺组织损伤均有改善,肺损伤评分及细胞凋亡率显著降低(P<0。05),肺组织GRP78、PERK、CHOP、Caspase-3、Caspase-9 mRNA 表达降低(P<0。05),GRP78、p-PERK、ATF4、CHOP、Caspase-3、Caspase-9 蛋白表达降低(P<0。05)。结论 芪蛭皱肺颗粒可通过抑制COPD大鼠内质网应激相关因子表达减少细胞凋亡过亢为害,从而促进未折叠蛋白反应提高内质网折叠能力,制约内质网应激状态,助其承制。
Effects of Qizhi Zhoufei Granules on Endoplasmic Reticulum Stress in Chronic Obstructive Pulmonary Disease Rats
Objective To investigate the effects of Qizhi Zhoufei Granules on endoplasmic reticulum stress in rats with chronic obstructive pulmonary disease(COPD);To explore its mechanism.Methods COPD rat model was induced by lipopolysaccharide tracheal instillation and smoking.Totally 60 Wistar rats were divided into control group,model group,Bufei Huoxue Capsules group and Qizhi Zhoufei Granules low-,medium-and high-dosage groups using random number table method,with 10 rats in each group.Drug gavage intervention was carried out for the treatment group since the 29th day of modeling,and normal saline was given to the control group and model group for 28 d.Lung function tests were performed,HE staining was used to detect morphology of lung tissue,TUNEL staining was used to detect the degree of apoptosis in lung tissue,RT-qPCR and Western blot were used to detect the endoplasmic reticulum stress and apoptosis related molecular mRNA and protein expression in lung tissue.Results Compared with the control group,the lung function indexes of peak inspiratory flow(PIF),peak expiratory flow(PEF)and minute volume(MV)significantly decreased,and frequency of breathing(F)significantly increased in the model group(P<0.05);the structural damage of the lung tissue was obvious,the lung injury score and apoptosis rate significantly increased(P<0.05),the expressions of glucose regulated protein 78(GRP78),protein kinase R-like ER kinase(PERK),C/EBP-homologous protein(CHOP),Caspase-3 and Caspase-9 mRNA were increased(P<0.05),the protein expressions of GRP78,p-PERK,activating transcription factor 4(ATF4),CHOP,Caspase-3 and Caspase-9 were significantly increased(P<0.05).Compared with the model group,PIF,PEF and MV significantly increased in Qizhi Zhoufei Granules medium-and high-dosage groups and Bufei Huoxue Capsules group,and F significantly decreased(P<0.05);the damage in lung tissue was improved,and the lung injury score and cell apoptosis rate significantly decreased(P<0.05),the mRNA expressions of GRP78,PERK,CHOP,Caspase-3 and Caspase-9 in lung tissue decreased(P<0.05),and the protein expressions of GRP78,p-PERK,ATF4,CHOP,Caspase-3 and Caspase-9 decreased(P<0.05).Conclusion Qizhi Zhoufei Granules can prevent cell apoptosis and excessive damage by inhibiting the expression of endoplasmic reticulum stress related factors in COPD rats,thereby promoting unfolded protein response and improving endoplasmic reticulum folding ability,constraining endoplasmic reticulum stress state,and assisting in its regulation.

Qizhi Zhoufei Granuleschronic obstructive pulmonary diseaseharmful hyperactivity checked and restrained to keep balanceendoplasmic reticulum stressrats

张毅、武金伟、蒋倩羽、李金田、赵鲲鹏、吴晓刚

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甘肃中医药大学中医临床学院,甘肃兰州 730000

兰州石化总医院(甘肃中医药大学第四附属医院),甘肃兰州 730060

芪蛭皱肺颗粒 慢性阻塞性肺疾病 亢害承制 内质网应激 大鼠

2025

中国中医药信息杂志
中国中医科学院中医药信息研究所

中国中医药信息杂志

影响因子:0.889
ISSN:1005-5304
年,卷(期):2025.32(1)