高压氧联合温肾益气颗粒对慢性阻塞性肺疾病大鼠气道炎症及氧化应激的影响及机制

Effect and mechanism of hyperbaric oxygen combined with Wenshenyiqi granules on airway inflammation and oxidative stress in rats with chronic obstructive pulmonary disease

目的探讨高压氧联合温肾益气颗粒对慢性阻塞性肺疾病(COPD)大鼠气道炎症及氧化应激的影响及机制。方法50只SD大鼠按体质量排序法随机分为对照组(生理盐水)、模型组(生理盐水)、温肾益气颗粒组(1.5 g/kg温肾益气颗粒)、高压氧组(0.20 MPa高压氧)、联合组(0.20 MPa高压氧+1.5 g/kg温肾益气颗粒),每组10只,除对照组外,其余组采用烟熏联合气道滴注脂多糖法建立COPD模型。建模后按照相应治疗方法持续治疗4周。比较各组肺功能及血气指标、肺泡灌洗液(BALF)中炎性因子、肺组织中氧化应激指标及过氧化物酶体增殖物激活受体γ(PPARγ)、核因子-κB(NF-κB)mRNA和蛋白表达。结果治疗4周后,对照组、模型组、温肾益气颗粒组、高压氧组和联合组第0.3 s用力呼气容积与用力肺活量比值(FEV0.3/FVC)分别为83.69±5.24、62.30±6.07、75.26±7.15、75.87±6.02、81.85±6.33,动脉血二氧化碳分压(PaCO_(2))分别为(48.61±3.10)mm Hg、(57.92±4.23)mm Hg、(54.14±3.19)mm Hg、(54.08±3.62)mm Hg、(49.32±3.87)mm Hg。与对照组比较,模型组FEV0.3/FVC降低、PaCO_(2)升高(P<0.05);与模型组比较,温肾益气颗粒组、高压氧组及联合组FEV0.3/FVC均升高、PaCO_(2)均降低(P<0.05);与温肾益气颗粒组和高压氧组相比,联合组FEV_(0.3)/FVC更高、PaCO_(2)更低(P<0.05)。与对照组比较,模型组BALF中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、单核细胞趋化蛋白-1(MCP-1)及肺组织中丙二醛(MDA)、NF-κB mRNA和蛋白相对表达量升高,超氧化物歧化酶(SOD)、PPARγmRNA和蛋白相对表达量降低(P<0.05);与模型组比较,温肾益气颗粒组、高压氧组及联合组BALF中TNF-α、IL-1β、MCP-1及肺组织中MDA、NF-κB mRNA和蛋白相对表达量均降低,且联合组低于温肾益气颗粒组和高压氧组(P<0.05);与模型组比较,温肾益气颗粒组、高压氧组及联合组肺组织中SOD、PPARγmRNA和蛋白相对表达量均升高,且联合组高于温肾益气颗粒组和高压氧组(P<0.05)。结论高压氧联合温肾益气颗粒能够对COPD大鼠气道炎症及氧化应激起到抑制作用,其作用机制可能与PPARγ信号通路有关。

Objective To investigate the effect and mechanism of hyperbaric oxygen combined with Wenshenyiqi granules on airway inflammation and oxidative stress in rats with chronic obstructive pulmonary disease(COPD).Methods A total of 50 SD rats were randomly divided into control group(normal saline),model group(normal saline),Wenshenyiqi granules group(1.5 g/kg Wenshenyiqi granules),hyperbaric oxygen group(0.20 MPa hyperbaric oxygen)and combination group(0.20 MPa hyperbaric oxygen+1.5 g/kg Wenshenyiqi granules)based on the order sorted by body mass,with 10 rats in each group.The COPD model was established in all the rats but the control group through smoking combined with airway infusion of lipopolysaccharide.After modeling,each group received treatment for 4 weeks according to the protocol.The pulmonary function,blood gas indicators,expressions of inflammatory factors in Bronchoalveolar Lavage Fluid(BALF),oxidative stress indicators in lung tissue,peroxisome proliferator activated receptorγ(PPARγ),nuclear factor-κB(NF-κB)mRNA,and protein expression were compared in each group.Results After 4 weeks of treatment,the ratio of forced expiratory volume at 0.3 s to forced vital capacity(FEV0.3/FVC)in the control group,the model group,the Wenshenyiqi granules group,the hyperbaric oxygen group,and the combination group was(83.69±5.24),(62.30±6.07),(75.26±7.15),(75.87±6.02),and(81.85±6.33),respectively.The arterial partial pressure of carbon dioxide(PaCO_(2))was(48.61±3.10),(57.92±4.23),(54.14±3.19),(54.08±3.62),and(49.32±3.87)mm Hg,respectively.Compared with the control group,the FEV0.3/FVC was decreased and PaCO_(2) increased in the model group(P<0.05).Compared with the model group,the FEV_(0.3)/FVC was increased in the Wenshenyiqi granules group,the hyperbaric oxygen group,and the combination group,while the PaCO_(2) was decreased(P<0.05).Compared with the Wenshenyiqi granules group and the hyperbaric oxygen group,the combination group had higher FEV0.3/FVC and lower PaCO_(2)(P<0.05).Compared with the control group,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),monocyte chemoattractant protein-1(MCP-1)in BALF,and malondialdehyde(MDA),expression levels of NF-κB mRNA and protein in lung tissues were increased in the model group,while superoxide dismutase(SOD),expression levels of PPARγmRNA and protein were decreased(P<0.05).Compared with the model group,TNF-α,IL-1β,and MCP-1 in BALF,MDA and expression levels of NF-κB mRNA and protein in lung tissues were decreased in the Wenshenyiqi granules group,the hyperbaric oxygen group,and the combination group,with those of the combination group were lower than those of the Wenshenyiqi granules group and the hyperbaric oxygen group(P<0.05).Compared with the model group,the SOD and expression levels of PPARγmRNA and protein in the lung tissues of the Wenshenyiqi granules group,the hyperbaric oxygen group,and the combination group were all increased,with those of the combination group were higher than those of the Wenshenyiqi granules group and the hyperbaric oxygen group(P<0.05).Conclusion Hyperbaric oxygen combined with Wenshenyiqi granules can effectively inhibit airway inflammation and oxidative stress in rats with COPD,which may be achieved through PPARγsignaling pathway.