The Molecular Mechanism Of Gentiana Veitchiorum Particles In The Treatment Of Chronic Bronchitis

Chronic bronchitis(CB)is a chronic inflammation of the bronchi in lung. It is generally considered one of the two forms of chronic obstructive pulmonary disease (COPD). It is defined clinically as a persistent cough that produces sputum (phlegm) and mucus. Disease progression can often complicated by obstructive pulmonary emphysema, or pulmonary hypertension, pulmonary heart disease The pathogenesis of chronic bronchitis remains unclear, Some factors, such as environmental pollution, smoking, infections, allergies, genetic, may be involved in the pathogenesis of CB. In recent years, with aging of population and increasing of air pollution, the incidence of CB is rising rapidly and CB affects seriously the people’s working ability as well as living quality. Now, the main treatment for CB is to take control of infections and expectorant, antitussive. There is still lack of specific efficacy of drugs for the treatment of CB. Therefore, it is of great significance to make deeper research on its pathological mechanism and develop the effective medicine.Gentiana veitchiorum Hemsl is gentian Gentianaceae part of the stem beyond, with detoxification, attending cough, bronchitis, sore throat, swollen and so on. Shiwei Longdanhua Tibetan medicine has good effect in treatment of chronic bronchitis, pulmonary infection of children. And it has the features of high efficiency and low toxicity. Alveolar macrophages (AM) are widely distributed in the surface of alveolar and airway epithelial, and are mainly immune cells in the lower respiratory tract, play an important regulatory role in the physiology and pathology of the lung.In this research, we will observe the effect of treatment about Gentiana veitchiorum on CB animal model, and the regulation of the balance of oxidation-antioxadation in animal lung tissue. We then will study the molecular mechanism of therapeutic effect in AM of lung tissue. Our studies will provide the experimental basis for developing new drugs for the treatment of chronic bronchitis. The research includes two parts as follows:1. Experimental research on Gentiana veitchiorum particle on the treatment of chronic bronchitisObjective: To investigate the protective effect of Gentiana veitchiorum on mice with chronic bronchitis.Methods: 60 female Kunming mice were randomly divided into 6 groups: control group,model group, the high, middle and low dose of Gentiana veitchiorum -treated groups and the complex tracheitis pellets-treated group. Except the control group, the mice in other groups inhaled NH3 using YLS-8A instrument to induce the chronic bronchitis. After 30 days, the treated groups were administrated with corresponding medicine i.g. for 15 days respectively. Control group received normal sodium (NS) only. The concentrations of SOD and MDA levels in pulmonic tissue bomogenate were measured. Pathology changes with HE stains were observed under light microscopy.Results: Compared with the model group, the contents of MDA in lung homogenate were decreased significantly and the contents of SOD were increased significantly in Gentiana veitchiorum -treated groups.HE stain showed an improvement of injury from chronic bronchitis after a treatment of Gentiana veitchiorum particle.Conclusion: Gentiana veitchiorum exhibited anti-bronchitis effects against NH3-induced bronchitis and can be used in preventing the development of bronchitis.2. The effect of Gentiana veitchiorum particles on the expression of TNF-αinduced by LPS in pulmonary alveolar macrophages.Objective: To investigate the effect of Gentiana veitchiorum particles on the expression of TNF-αin pulmonary alveolar macrophages (AM) which induced by LPS, to explain the mechanism about anti-inflammatory action of Gentiana veitchiorum particles.Methods: Purification of rat AM, TNF-αlevel in AM culture supernatant was detected by ELISA. Western blot method for detecting the expression of TNF-αand pERK in the AM. While application of ERK antagonist (PD98059) in rat AM and the expression of TNF-αwas observed by Western blot.Results: Gentiana veitchiorum particles can reduce the LPS induced AM TNF-αincrease in dose dependent manner. Gentiana veitchiorum particles (100mg/L) can significantly reduce the LPS induced pERK and TNF-αprotein expression in AM. Compared with LPS stimulation group, TNF-αprotein expression were significantly reduced in rat AM in ERK inhibitor(PD98059), Gentiana particles and Gentiana veitchiorum particles plus PD98059 groups.Conclusion: Gentiana veitchiorum particles can inhibit the LPS induced pulmonary AM TNF-αexpression, one of the possible mechanism is to inhibit the extracellular signal transduction pathway.