摘要
目的探究人参皂苷Rg1对大鼠阻塞性睡眠呼吸暂停低通气综合征(OSAHS)引起的肺损伤及Nrf2/HO-1信号通路的影响及机制。方法60只SD大鼠分为对照组(control组)、慢性间歇性缺氧组(CIH组)、人参皂苷Rg1低剂量组(CIH+GRg1-L)和人参皂苷Rg1高剂量组(CIH+GRg1-H),每组15只。使用低氧舱建立CIH模型,并对CIH模型进行鉴定;动物肺功能分析系统测定各组大鼠的肺功能;试剂盒检测各组大鼠肺组织中丙二醛(MDA)、谷胱甘肽(GSH)的含量和超氧化物歧化酶(SOD)的活性;ELISA检测各组大鼠肺组织中肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和白介素-6(IL-6)的含量;HE染色观察各组大鼠肺组织的病理变化;qRT-PCR和Western blot检测各组大鼠肺组织中环氧合酶-2(COX-2)、诱导型一氧化氮合酶(iNOS)、核转录因子2(Nrf2)和血红素加氧酶-1(HO-1)的表达。结果造模组大鼠的生理特征接近OSAHS病理生理特点,因此CIH动物模型建立成功。CIH组大鼠的深吸气量(IC)、最大呼气流速(PEF)、第0.3秒用力呼气后的容积(FEV0.3)及每分钟呼气量(VE)明显降低(P<0.01),而人参皂苷Rg1使大鼠的IC、PEF、FEV0.3及VE升高(P<0.01);CIH组大鼠肺组织中MDA的含量明显增加(P<0.01),SOD的活性和GSH的含量明显降低(P<0.001,P<0.01),TNF-α、IL-1β和IL-6的含量显著增加(P<0.01),人参皂苷Rg1使大鼠肺组织中MDA的含量降低(P<0.05),SOD活性和GSH含量升高(P<0.05),TNF-α、IL-1β和IL-6的含量降低(P<0.05);CIH组大鼠肺组织严重受损,肺泡中可见炎性细胞浸润,而人参皂苷Rg1使大鼠肺组织受损减轻,炎性细胞浸润减少;CIH组大鼠肺组织中COX-2、iNOS、Nrf2、HO-1 mRNA和蛋白表达水平显著上调(P<0.001),人参皂苷Rg1使大鼠肺组织中COX-2、iNOS、Nrf2、HO-1 mRNA和蛋白表达水平下调(P<0.05)。结论人参皂苷Rg1能改善大鼠肺功能,减轻氧化应激反应和炎症因子的表达,下调Nrf2和HO-1蛋白的表达。
Objective To investigate the effect of ginsenoside Rg1 on lung injury and Nrf2/HO-1 signaling pathway caused by obstructive sleep apnea-hypopnea syndrome(OSAHS) in rats and its mechanism.Methods Totally 60 SD rats were divided into control group(control group),chronic intermittent hypoxia group(CIH group),ginsenoside Rg1 low-dose group(CIH+GRg1-L),and ginsenoside Rg1 high-dose group(CIH+GRg1-H),15 in each group.A hypoxic chamber was used to establish a CIH model and the CIH model was identified.Animal lung function analysis system was used to measure lung function of rats in each group.The kit was used to detect the contents of malondialdehyde(MDA),glutathione(GSH) and the activity of superoxide dismutase(SOD) in the lung tissue of each group of rats.ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β) and interleukin-6(IL-6) in lung tissue of rats in each group.HE staining was used to observe the pathological changes of lung tissue in each group of rats.The qRT-PCR and Western blot were used to detect the expression of cyclooxygenase-2(COX-2),inducible nitric oxide synthase(iNOS),nuclear transcription factor 2(Nrf2),and heme oxygenase-1(HO-1).Results The physiological characteristics of model rats were close to the pathophysiology of OSAHS,so the CIH animal model was successfully established.In the CIH group, the inspiratory capacity(IC),peak exspiratory flow(PEF),forced expiratory volume(FEV)0.3,and ventilation volume per minute(VE) were significantly reduced(P<0.01),while ginsenoside Rg1 increased IC,PEF,FEV0.3 and VE in rats(P<0.01).The content of MDA in lung tissue of rats in CIH group increased significantly(P<0.01),while the activity of SOD and GSH content decreased significantly(P<0.001,P<0.01),and the contents of TNF-α,IL-1β and IL-6 significantly increased(P<0.01).Ginsenoside Rg1 decreased MDA content in lung tissue of rats(P<0.05),increased SOD activity and GSH content(P<0.05),and reduced TNF-α,IL-1β,and IL-6 content(P<0.05).In the CIH group, the lung tissue was severely damaged, and inflammatory cells infiltrated in the alveoli, while ginsenoside Rg1 reduced the damage to the lung tissue and the inflammatory cell infiltration.The expression levels of COX-2,iNOS,Nrf2,HO-1 mRNA and proteins in the lung tissue of rats in CIH group were significantly up-regulated(P<0.001),while ginsenoside Rg1 down-regulated the expression of COX-2,iNOS,Nrf2,HO-1 mRNA and proteins in rat lung tissues(P<0.05).Conclusion Ginsenoside Rg1 can improve lung function in rats, reduce oxidative stress and expression of inflammatory factors, and down-regulate the expression of Nrf2 and HO-1 proteins.
作者
田婵婵
王宏志
马欣悦
TIAN Chan-chan;WANG Hong-zhi;MA Xin-yue(Department of Respiratory Medicine,the Second People′s Hospital of Yichang,the Second People′s Hospital of Three Gorges University,Yichang 443000,China;Department of Gastroenterology,Huangshi Central Hospital of Hubei Institute of Technology,Affiliated Hospital of Hubei Institute of Technology,Huangshi 435000,China;School of Medicine,Three Gorges University,Yichang 443002,China)
出处
《实用药物与临床》
CAS
2021年第4期294-300,共7页
Practical Pharmacy and Clinical Remedies
基金
湖北省卫生健康委科研项目(WJ2019M067)。
