Studies On The Anti-inflammatory Molecular Mechanisms Of Triterpene Acids Of Loquat.Leaf In Chronic Bronchitis

The anti-inflammatory mechanisms of Triterpene Acids of Loquat.Leaf (TAL) in chronic bronchitis were studied by using the method in vivo and in vitro. Owing to the importance of (AM) in the processor of chronic bronchitis, effects of TAL on AM functions were investigated. The main contents are divided into some sections as follows:1. Model establishingCombining utilization of BCG (5mg.kg-1, injected through caudal vein) and LPS (200μg, injected through endotracheal intubation one week after BCG injection), the typical morphologic changes of chronic bronchitis were induced after 3 weeks. It is established that the new method by combining utilization of BCG and LPS is convenient and simple for the longitudinal study on the mechanism of initiation and progress of chronic bronchitis.2. Effect of TAL on AM formation and activationTAL significantly inhibited the abnormal increased activation of AM and highly inhibited the change of AM formation.3. Effect of TAL on NF-kB expression and TNF-α IL-1 levels in AM of CB rats. TAL(150,450 mg.kg-1 ig) markedly reduced the increased TNF-a and IL-1 levelsin cultured supernatants of AM in CB rats. TAL(50,150,450 mg.kg-1 ig) obviously decreased the increased expression of NF-kB in AM in a dose dependent manner. The results showed that the anti-inflammatory effect of TAL on CB rats was probably related to its inhibition of cytokines expression in AM.4. Effect of TAL on LTB4 > PGE2 generation in AM of CB rats.TAL(150> 450 mg-kg'1 ig) could not only highly inhibit LTB4 generation but also affect PGE2 production from AM at a dose of 450 mg-kg'1. Results above illustrated that the anti-inflammatory effect of TAL on CB rats was probably correspondent to its reducing of inflammatory mediums expression in AM.5. Effect of TAL on SOD activity and MD A level in AM of CB rats.In order to investigate the relationship between the ROS and chronic bronchitis, SOD and MDA concentrations in AM of CB rats were measured. We found that TAL(150^ 450 mg-kg"1 ig) not only significantly inhibited MDA generation but also increased the SOD production from AM of CB rats.6. Effect of TAL on iNOS expression and NO releasing in AM of CB rats.To supply the anti-inflammatory mechanism study of TAL, we also detected the change of iNOS in AM of CB rats. It is well known that iNOS and NO are important in inflammation and NO could induce lung injury. In this study, it was found that iNOS and NO levels were evidently increased while TAL significantly decreased the increased iNOS and NO levels, which might be another anti-inflammatory mechanism of TAL.7. Effect of TAL on HO-1 activity in lung tissue and expression in AM of CB rats. TAL(150> 450 mg-kg"1 ig) apparently decreased the increased expression of HO-1 inAM and lung tissue of CB rat at mRNA and protein levels in a dose dependent manner. These results showed that the anti-inflammatory effect of TAL on CB rats was probably correspondent to its reducing ROS generation and modulating oxide-antioxide balance.8. Effect of L-Arg and L-NAME on HO-1 mRNA expression in AM of CB ratsL-Arg( 10"5, 10"4 > 10"3 > 10"2 mol/L)could increase HO-1 mRNA expression in AM of CB rats in a dose dependent manner, while L-NAME(250umol/L) reversed the effect of L-Arg on HO-1 expresion. The result suggested that iNOS and its production NO take part in modulation of HO-1 expression. TAL inhibited HO-1 expression in AM by...