基于PI3K/Akt/HIF-1α信号通路探究厚朴大黄汤治疗慢性阻塞性肺疾病急性加重期大鼠的作用机制  

Exploring the Mechanism of Houpu Dahuang Decoction in Treating Acute Exacerbation of Chronic Obstructive Pulmonary Disease Rats Based on the PI3K/Akt/HIF-1α Signaling Pathway

作　　者：张晋 王硕 邱昌龙 Zhang Jin;Wang Shuo;Qiu Changlong(School of Traditional Chinese Medicine,North China University of Science and Technology,Hebei,Tangshan 063000,China)

机构地区：[1]华北理工大学中医学院,河北唐山063000

出　　处：《中国中医急症》2025年第4期602-606,619,共6页Journal of Emergency in Traditional Chinese Medicine

基　　金：国家中医药管理局第五批临床优秀人才项目(202201);河北省科普专项(19K57772D)。

摘　　要：目的 基于PI3K/Akt/HIF-1α信号通路探究厚朴大黄汤治疗慢性阻塞性肺疾病急性加重期(AECOPD大鼠的作用机制。方法 雄性SD大鼠62只,随机选取10只为空白组,余52只采用气管滴注LPS及香烟熏染制备大鼠模型后随机分为模型组12只、多索茶碱组10只及厚朴大黄汤高、中、低剂量组各10只。多索茶碱组给予0.06 g/mL的多索茶碱混悬液,厚朴大黄汤低、中、高剂量组每日分别按8.22、16.43、32.86 g/kg灌胃治疗。苏木素-伊红(HE)染色观察大鼠肺、肠组织病理学变化;ELISA检测各组血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)及肺、结肠组织SIgA含量;免疫组化、Western blotting检测肺组织PIK3CA、Akt1、HIF-1α及肠组织Occludin蛋白。结果 相比于空白组,模型组大鼠肺、肠病理学改变明显,肺部湿/干比表达升高(P <0.01),血清IL-6、TNF-α表达增高(P <0.01),WB检测PIK3CA、Akt1、HIF-1α蛋白表达比值升高(P <0.01),结肠组织Occludin蛋白表达减少(P <0.01);对比AECOPD模型组,厚朴大黄汤低、中、高剂量组肺湿/干比明显降低(P <0.01),多索茶碱组肺湿/干比降低(P <0.05);多索茶碱组、厚朴大黄汤低剂量组、厚朴大黄汤中剂量组IL-6、TNF-α水平显著下降(P <0.01),厚朴大黄汤中、低剂量组及多索茶碱组肺组织SIgA增加显著(P <0.01),WB检测治疗组肺组织PIK3CA、Akt1、HIF-1α蛋白表达降低(P <0.01);免疫组化多索茶碱组及厚朴大黄汤中剂量组PIK3CA、Akt1、HIF-1α蛋白表达显著降低(P <0.01)。结论 厚朴大黄汤可能通过抑制PI3K/AKT/HIF-1α信号通路活化达到治疗AECOPD的作用。Objective:To explore the mechanism of Houpu Dahuang Decoction in treating acute exacerbation of chronic obstructive pulmonary disease(AECOPD)rats based on the PI3K/Akt/HIF-1αsignaling pathway.Methods:Sixty-two male SD rats were divided into groups;ten rats served as the blank control group,while the remaining fty-two were used to establish an AECOPD model through intratracheal instillation of LPS and cigarette smoke exposure.The doxofylline group was treated with a 0.06 g/mL doxofylline suspension,whereas the Houpu Dahuang Decoction low,medium,and high dose groups were administered 8.22,16.43,and 32.86 g/kg daily via gavage,respectively.Hematoxylin-eosin(HE)staining was used to observe pathological changes in lung and intestinal tissues.ELISA was employed to measure serum IL-6,TNF-αlevels,and secretory immunoglobulin A(SIgA)content in lung and colon tissues.Immunohistochemistry and Western blotting(WB)were utilized to detect protein expression of PIK3CA,Aktl,HIF-lαin lung tissues and Occludin in intestinal tissues.Results:Compared with the blank group,AECOPD model rats exhibited significant pathological changes in lung and intestinal tissues,increased lung wet-to-dry weight ratios(P<0.01),elevated serum IL-6 and TNF-αlevels(P<0.01),increased PIK3CA,Akt1,HIF-1αprotein expression ratios detected by WB(P<0.01),and reduced Occludin protein expression in colon tissues(P<0.01).Compared with the AECOPD model group,the Houpu Dahuang Decoction low,medium,and high dose groups significantly reduced lung wet-to-dry weight ratios(P<0.01),and the doxofylline group also showed a reduction(P<0.05).In the doxofylline group and the Houpu Dahuang Decoction low and medium dose groups,IL-6 and TNF-αlevels decreased significantly(P<0.01),and SIgA levels in lung tissues increased notably(P<0.01).Treatment groups demonstrated decreased PIK3CA,Aktl,HIF-1αprotein expression(P<0.01);immunohistochemical analysis revealed significant decrease in PIK3CA,Aktl,HIF-1αprotein expression in the doxofylline and Houpu Dahuang Decoction mediu

关 键 词：慢性阻塞性肺疾病急性加重期 厚朴大黄汤 PI3K/Akt/HIF-1α信号通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]