Effects Of Ligustrazine On Th1/Th2 Cytokines In A Rat Asthma Model And Underlying Mechanism

Bronchial asthma is a chronic inflammatory disorder of airways. Many inflammatory cell and cytokines are involved in this process– eosinophils, T lymphocytes and mast cells. In particular, it has been shown, in patients with asthma and in animal models, that chronic airway inflammation is associated with increased T helper (Th) 2 cytokine production and decreased Th1 cytokine production. Asthma is therefore considered a Th2-driven disease in which the presence of Th2 cells correlates with IgE production, mast cell hyperplasia, and eosinophil infiltration, determining the severity of the disease. The differentiation of naive CD4+ T cells into Th1 or Th2 effector cells is a critical process during immune responses. Several investigators have shown that T-bet and GATA-3 are the key transcription factors for differentiation toward Th1 and Th2 cells. Glucocorticosteroids are by far the most effective anti-inflammatory agents used for treatment of asthma; however, severe systemic side effects are associated with their long-term use. Ligustrazine is an alkaloid isolated from the rhizome of Ligusticum chuanxiong Hort, which is known as Chuanxiong in Chinese. The alkaloid ligustrazine has the chemical name 2, 3, 5, 6- tetramethylpyrazine. Ligustrazine is reported to possess a very broad spectrum of pharmacological actions, such as immunomodulative, anti-platelet aggregation, antioxidant, anti-inflammatory, anti-fibrosis and antitumour effects. Ligustrazine is widely used for the treatment of cardio-cerebral vascular diseases and it is also used clinically to treat asthma. Recent study indicated that ligustrazine could suppress airway inflammation in asthmatic rats. However, the mechanism remains unclear. Exploring the effects of ligustrazine on airway inflammation and the underlying mechanism will afford experimental evidence for clinical use of ligustrazine. PartⅠEffects of Ligustrazine on Airway Inflammation in A Rat Asthma ModelObjective To investigate the effects of intraperitoneal ligustrazine on airway inflammation in a rat asthma model.Methods Forty male SD rats were randomly divided into 5 groups: normal control group, asthmatic model group, asthmatic control group, dexamethasone (Dex) group and ligustrazine group. Total and differential cell counts in BALE were measured, and lung tissues were embedded in paraffin for histological analysis by HE staining.Results(1)The number of total cells, percentages of EOS and neutrophil in the BALF of asthmatic group and asthmatic control group were both significantly increased compared to normal control group (P < 0.05). However, they were significantly reduced after administration of ligustrazine compared with the asthmatic rats (P < 0.05), but were significantly increased compared to the normal control rats (P < 0.05). The number of total cells, percentages of EOS, neutrophil and lymphocyte were all decreased in Dex group (P < 0.05).(2)In the asthmatic group, a massive peribronchial infiltration of inflammatory cells, thickening of bronchial wall and area of smooth muscle, and occlusion of the bronchial lumen by mucus and inflammatory cells. However, ligustrazine treatment resulted in an intact bronchial epithelial layer and few inflammatory cells infiltration, the same features shown in the dexamethasone group.ConclusionIntraperitoneal ligustrazine inhibits OVA induced airway inflammation. PartⅡEffects of Ligustrazine on Th1/Th2 Cytokines in A Rat Asthma Model and Underlying MechanismObjective To investigate the effects of intraperitoneal ligustrazine on Th1/Th2 cytokines in a rat asthma model and the underling mechanism.Methods Forty male SD rats were randomly divided into 5 groups: normal control group, asthmatic model group, asthmatic control group, dexamethasone (Dex) group and ligustrazine group. The concentrations of IL-4 and IFN-γin bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosobent assay (ELISA). The protein expressions of GATA-3 and T-bet in pulmonary tissue were detected with immunohistochemical assay and measured by Western blot.Results(1)In asthmatic and asthmatic control group, the levels of IL-4 in BALF and the expression of GATA-3 of lung were higher than those in normal control group (P < 0.05), while the levels of IFN-γand T-bet were significantly decreased (P < 0.05).(2)Compared with asthmatic group and asthmatic control group, the levels of IL-4 in BALF and the expression of GATA-3 of lung tissue in ligustrazine group were both lower (P < 0.05), and the levels of IFN-γand T-bet were both higher (P < 0.05), while all of IL-4, IFN-γ, GATA-3 and T-bet decreased in Dex group (P < 0.05), but the decreasing degree of IL-4, GATA-3 were greater than that of IFN-γ, T-bet, respectively.(3)Correlation analysis showed that in asthmatic rats, the level of IL-4 in BALF was positively correlated with the expression of GATA-3 protein of lung tissue(r=0.86,P < 0.05), and the level of IFN-γwas positively correlated with the expression of T-bet.(r=0.82,P < 0.05). Conclusion Ligustrazine inhibits OVA induced airway inflammation by modulating key master switches GATA-3 and T-bet that result in reversing the Th2 cytokine patterns in asthma. ObjectiveTo study the clinic characteristics and the relation of histopathology with age, gender, location and the sign of fibrobronchoscopy in lung cancer patients diagnosed by fibrobronchoscopy under 40 years of age.MethodsWe analyzed retrospectively the fibrobronchoscopy data of 104 young lung cancer patients enrolled between January 1980 and December 2004.ResultsOf the 104 patients, the male/female ratio was 1.6/1.0. Compared to the more common older patients, the young patients had an increased percentage of women (P < 0.05). The most common histopathology was squamous cell carcinoma (39.8 %), followed by small cell carcinoma (26.1%) and adenocarcinoma (22.7 %) in 88 young patients with histologically proven lung cancer. Among 104 young lung cancer patients, 75.0 % had direct sign, and 25.0 % had indirect sign. Most squamous cell carcinoma had cauliflower-like tumour, most small cell carcinoma had polypus-like tumour or infiltrative lesion, while most adenocarcinoma had polypus-like tumour or indirect sign. There were not obviously different about the cancer's distribution between left and right lungs (P > 0.05) while the location of squamous cell carcinoma was more in the right lung (P < 0. 05).ConclusionThis study suggests fibrobrochoscopy is an important approach in diagnosis of young lung cance. Paying more attention to the lung cancer of young patients and examining with fibrobronchoscopy would be helpful to earlier diagnosis.