中医药调控氧化应激相关信号通路防治支气管哮喘研究进展

Traditional Chinese Medicine Regulates Oxidative Stress-related Signaling Pathways to Prevent and Treat Bronchial Asthma:A Review

支气管哮喘(简称哮喘)是一种临床常见的呼吸系统疾病,以气道出现慢性炎症反应为主要特征,发病机制繁杂,治疗周期漫长,缠绵难愈,且无特效药。氧化应激是哮喘发病机制研究中的新热点,也是其治疗的潜在关键靶标。生理状况下,体内氧化与抗氧化系统处于动态平衡,两者相互拮抗共同维持机体正常生命活动。哮喘发病阶段,活性氧(ROS)、丙二醛(MDA)、一氧化氮(NO)等氧化产物过量产生,超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽(GSH)等抗氧化剂含量降低,氧化程度超出氧化物的清除,使氧化应激水平大幅提高。另外,ROS的过量生成,会激活氧化应激相关信号通路,产生促炎因子,加剧炎症反应。从而导致哮喘患者肺部和气道组织损伤。近年来,中医药在哮喘治疗中的优势得到国内外专家学者的关注,尤其在调节氧化还原平衡缓解哮喘患者氧化应激、减少炎症反应等方面已取得显著成效。中医药一方面通过抑制丝裂原活化蛋白激酶(MAPK)、核转录因子-κB(NF-κB)相关信号通路,从源头上降低氧化产物和促炎因子的含量;另一方面通过激活核因子E2相关因子2(Nrf2)相关信号通路,上调抗氧化酶的水平,增强抗氧化系统以中和过量堆积的氧化产物。因此,以中医药调节氧化平衡状态作为诊疗思路,可能是未来防治哮喘的新手段、新方向。该文章对氧化应激相关通路参与哮喘发病机制进行系统阐述,同时对中药提取物、中药复方调控氧化应激相关通路治疗哮喘的最新研究进行梳理,以期为中医药防治哮喘临床和基础研究的开展提供更充分、更坚实、更科学的理论依据。

Bronchial asthma(asthma for short)is a common clinical respiratory disease mainly characterized by chronic airway inflammation,with complicated pathogenesis and a long treatment cycle.It is lingering and difficult to be cured,and lack specific drugs.Oxidative stress is a new focus in the research on the pathogenesis of asthma and a potential key target for the treatment.Under physiological conditions,the oxidative and antioxidative systems in the body are in a dynamic balance,and the two antagonize each other to maintain normal life activities.In the case of asthma attack,oxidation products such as reactive oxygen species(ROS),malondialdehyde(MDA),and nitric oxide(NO)are produced excessively,while the content of antioxidants such as superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)is reduced.As a result,the oxidation exceeds the removal of oxidation products,which aggravates oxidative stress.In addition,the overproduction of ROS activates oxidative stress-related signaling pathways to produce pro-inflammatory factors,exacerbating inflammation,which leads to lung and airway tissue damage.In recent years,traditional Chinese medicine has garnering increasing attention because of the unique advantages in the treatment of asthma,especially in regulating redox balance,alleviating oxidative stress in asthma patients,and reducing inflammation.On the one hand,by inhibiting the mitogen-activated protein kinase(MAPK)and transcription factor(NF)-κB signaling pathways,traditional Chinese medicine can reduce the content of oxidation products and pro-inflammatory factors from the source.On the other hand,by activating the nuclear factor-erythroid 2-related factor 2(NrF2)signaling pathway,traditional Chinese medicine can elevate the levels of antioxidant enzymes and enhance the antioxidant system to neutralize the excessive accumulation of oxidation products.Therefore,the adjustment of redox balance state by traditional Chinese medicine may be a new means and a new direction for the prevention and treatment of asthma in the future.This paper summarizes the oxidative stress-related pathways in the pathogenesis of asthma and reviews the latest research progress in the regulation of oxidative stress-related pathways by Chinese medicine extracts and prescriptions in the treatment of asthma,with a view to providing a fuller,more solid,and more scientific theoretical basis for the clinical and basic research on the prevention and treatment of asthma by traditional Chinese medicine.