| Bronchial asthma is one of the common diseases in the world. The incidence of asthma has increased substantially in the last two decades. With the development of molecular pathology and immunology, we have known that the nature of asthma is airway inflammation. But by now the pathogenesis and the prevalence of asthma are incompletely understood. Many recent studies suggest that oxidant stress plays an important role in the pathogenesis of asthma. Heme oxygenase-1 (HO-1) can be stimulated by a variety of inducers that can produce reactive oxygen species (ROS). Alveolar macrophages (AMs) represent the cell population mainly responsible for HO-1 expression in the lungs. It is suggested that HO-1 participated in allergic inflammation. However, the exact role of HO-1 in airway inflammation has not been cleared. This study aimed to observe HO-1 expression in rat model of the asthma and hypoxic pulmonary hypertension (HPH), and speculated the relationship between HO-1 expression and pathological changes in asthma and HPH. Meantime we observed the effects of stimulator and inhibitor of HO-1 on the production of tumor necrosis factor-α (TNF-α) and the proliferation of lymphocytes (LC) by cultured AMs.Chinese herbs 814, is a new drug developed by Blood Institute of CAMS. We have reported that 814 may prevent and cure elastase-induced emphysema and smoking-induced chronic obstructive pulmonary disease (COPD) in the hamsters. But the effect of 814 on asthma has not been performed before. In this study, we observed the effect of 814 on rat asthma and HPH, and observed the effect of 814 on the expression of HO-1, and the relationship between HO-1, TNF-α, lymphoproliferation, eNOS and iNOS.The main experimental results are as follows:1. Development of rat asthma model and the effect of Chinese herbs 814: 72 of four-weeks old SD rats were randomly divided into 6 groups: normal (N); model (M); small (Ts), medial (Tm), large (Tl) dose 814 (2,5g, 25g, and 50g crude drug/kg/day respectively); and Aminophylline (35mg/kg/day) group. To establish asthma model, the rats were sensitized by a single intraperitoneal injection of 100 mg ovalbumin (OVA), 2 weeks later, the rats were challenged by inhaling 1.0% OVA for 20 minutes. This antigen challenge was repeated once a day for 2 weeks. The N group were challenged with saline. The results: airway responsiveness to acetylcholine, total cell number, eosinophils (EO) and Malondialdehyde (MDA) concentration in the bronchoalveolar lavage fluid (BALF), circulating endothelial cells (CEC) in blood were significantly increased in M group than those in N group (P<0.05 or P<0.01). Superoxide dismutase (SOD) activity in BALF was significantly decreased in M group than that in N group (P<0.01). The lung morphometry revealed that the number of LC, EO, mast cells infiltration in the bronchi and the proportion of goblet cells were significantly increased in M group than those in N group (P<0.05 or P<0.01). Under electron microscope there were pathological changes in bronchial and lung tissues in M group. It was indicated that the asthma model of rat was developed successfully. Tm and Tl dose 814 improved the above-mentioned targets as effectively as Aminophylline, but 814 protected bronchial epithelium and vascular endothelium better than Aminophylline. The effect of Ts 814 was not obvious.
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