文献类型：期刊文献

中文题名：宣肺止嗽颗粒通过PI3K/AKT信号通路抑制COPD大鼠的炎症机制

英文题名：Anti-Inflammatory Mechanism of Xuanfei Zhisou(宣肺止嗽)Granules on COPD through PI3K/AKT Signaling Pathway

作者：魏雪艳[1];王云超[2];何锦[3];杨震[1];王新华[1];马晓明[4]

第一作者：魏雪艳

机构：[1]甘肃中医药大学公共卫生学院,兰州730000;[2]甘肃中医药大学基础医学院,兰州730000;[3]甘肃省人民医院重症医学科,兰州730000;[4]兰州市肺科医院,兰州730000

第一机构：甘肃中医药大学公共卫生学院

年份：2024

卷号：40

期号：12

起止页码：41

中文期刊名：中药药理与临床

外文期刊名：Pharmacology and Clinics of Chinese Materia Medica

收录：;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

基金：国家重点研发项目(编号:2017YFC0907202);甘肃省科技计划项目(编号:22ZY1QA003);甘肃省高等学校产业支撑计划项目(编号:2022CYZC-53);甘肃省自然科学基金(编号:22JR5RA682)。

语种：中文

中文关键词：宣肺止嗽颗粒;慢性阻塞性肺疾病;炎症;磷脂酰肌醇3激酶/蛋白激酶B信号通路

外文关键词：Xuanfei Zhisou(宣肺止嗽)Granules;Chronic obstructive pulmonary disease;Phosphatidylinositol 3 kinase/protein kinase B signaling pathway;Inflammation

摘要：目的:验证宣肺止嗽颗粒在慢性阻塞性肺疾病(COPD)中的抗炎作用,并探讨其基于PI3K/AKT信号通路对COPD大鼠的作用机制。方法:将60只雄性Wistar大鼠随机选择10只为正常对照组,剩余50只用烟熏(CS)联合气管滴注脂多糖(LPS)诱导COPD发生,模型成功后随机分为模型对照组、宣肺止嗽颗粒0.9、1.8、3.6 g/kg组和地塞米松2.6×10^(-4)g/kg组,每组10只,连续灌胃28 d。干预结束后观察大鼠一般情况并检测肺功能,收集血清、肺组织;ELISA测定血清炎性因子白细胞介素6(IL-6)、IL-8、IL-1β、肿瘤坏死因子α(TNF-α)含量;HE染色进行肺组织病理检测;RT-PCR法检测肺组织Pi3k、Akt、Pip3、Pdk1、Ikb、Nfkb p65 mRNA表达;Western blot法检测肺组织PI3K、p-PI3K、AKT和p-AKT蛋白表达;IHC法测定大鼠肺组织p-AKT、p-NF-κB p65和IKB的蛋白表达。结果:与正常对照组比较,模型对照组大鼠肺功能降低(P<0.01),血清炎性因子IL-1β、IL-6、IL-8、TNF-α含量显著升高(P<0.01),肺组织Pi3k、Akt、Pip3、Pdk1、Nfkb p65 mRNA表达显著上调,Ikb mRNA表达显著下调(P<0.01),p-PI3K/PI3K、p-AKT/AKT比值显著升高(P<0.01),p-AKT和p-NF-κB p65蛋白阳性细胞数量明显升高(P<0.05或P<0.01),IKB蛋白阳性细胞数量显著降低(P<0.01);与模型对照组比较,宣肺止嗽颗粒0.9、1.8、3.6 g/kg组和地塞米松组大鼠肺功能显著改善(P<0.01),血清中炎性因子IL-1β、IL-6、IL-8、TNF-α含量明显降低(P<0.05或P<0.01),肺组织Pi3k、Akt、Pip3、Pdk1、Nfkb p65 mRNA表达明显下调(P<0.05或P<0.01),Ikb mRNA表达上调(P<0.05或P<0.01),p-PI3K/PI3K、p-AKT/AKT比值显著降低(P<0.01),p-AKT和p-NF-κB p65蛋白阳性细胞数量明显下降(P<0.05或P<0.01),IKB蛋白阳性细胞数量明显升高(P<0.01)。结论:宣肺止嗽颗粒可有效减弱COPD大鼠炎症反应,其机制可能是通过调控PI3K/AKT信号通路蛋白的表达,抑制IL-1β、IL-6、IL-8和TNF-α释放,进而缓解炎症反应对COPD大鼠的影响,改善肺功能。
Objective:To verify the anti-inflammatory effect of Xuanfei Zhisou(宣肺止嗽)Granules in chronic obstructive pulmonary disease(COPD)and explore its mechanism against COPD in rats based on the PI3K/AKT signaling pathway.Methods:Sixty male Wistar rats were randomly selected as the normal control group,and the remaining 50 rats were induced by smoking(CS)combined with tracheal instillation of lipopolysaccharide(LPS)to develop COPD.After successfully modeling,rats were randomly divided into a model control group,Xuanfei Zhisou Granule groups of 3.60,1.80,and 0.90 g/kg,and dexamethasone group of 2.58×10^(4) g/kg,with 10 rats in each group,and the drugs were continuously gavaged for 28 days.After the intervention,the general situation of each group of rats was observed,and lung function was detected.Serum and lung tissue were collected.Enzyme-linked immunosorbent assay(ELISA)was used to measure the serum contents of interleukin-6(IL-6),interleukin-8(IL-8),interleukin-1β(IL-1β),and tumor necrosis factorα(TNF-α).Hematoxylin-eosin(HE)staining was used for pathological observation of lung tissue.Reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the mRNA expressions of Pi3k,Akt,Pip3,Pdk1,Ikb,and Nf-κb p65 in the lung tissue.Western blot was used to detect the protein expressions of PI3K,p-PI3K,AKT,and p-AKT in the lung tissue.Immunohistochemistry(IHC)was used to measure the protein expressions of p-AKT,p-NF-κB p65,and IKB in the lung tissue.Results:Compared with that in the normal control group,the lung function of rats was decreased in the model control group(P<0.01).The serum contents of IL-1β,IL-6,IL-8,and TNF-αwere significantly increased(P<0.01).The mRNA expressions of Pi3k,Akt,Pip3,Pdk1,and Nf-κb p65 were significantly up-regulated,while the mRNA expression of Ikb was significantly down-regulated(P<0.01).The ratio of p-PI3K/PI3K and p-AKT/AKT was increased significantly(P<0.01).The number of positive cells of p-AKT and p-NF-κB p65 protein was increased significantly(P<0.05 or P<0.01),while that of positive cells of IKB protein was decreased significantly(P<0.01).Compared with the model control group,the lung function of rats in the Xuanfei Zhisou Granule groups of 3.60,1.80,and 0.90 g/kg and the dexamethasone group was significantly improved(P<0.01).The serum contents of IL-1β,IL-6,IL-8,and TNF-α were significantly decreased (P<0. 05 or P<0. 01). The mRNA expressions of Pi3k,Akt,Pip3,Pdk1,and Nf-κb p65 were significantlydown-regulated (P<0. 05 or P<0. 01),while the mRNA expression of Ikb was up-regulated (P<0. 05 or P<0. 01). The ratios of p-PI3K/PI3K and p-AKT/ AKT was were decreased significantly (P<0. 01). The number of positive cells of p-AKT and p-NF-κB p65 proteins wasdecreased significantly (P<0. 05 or P<0. 01),while the number of positive cells of IKB protein was increased significantly (P<0. 01). Conclusion:Xuanfei Zhisou Granules can effectively weaken the inflammatory reaction in rats with COPD,and its mechanism may be related toregulating the expression of proteins in the PI3K/ AKT signaling pathway and inhibiting the release of IL-1β,IL-6,IL-8,and TNF-α,therebyalleviating the impact of inflammation on rats with COPD and improving their lung functions.