| Tryptanthrin, a kind of indoles quinoline alkaloid, extracted from Isatis tinctoria, has some pharmacological activities such as anti-inflammator, anti- eumycete, and anti-tumor, etc.. Recent research has demonstrated that tryptanthrin could inhibit formation of leukotriene, prostaglandin, NO, NOS, etc. which were related to asthma. However, whether trytanthrin has some effects on asthma has not been reported. Our study was to investigate the effect of trytanthrin on asthma and its mechanism of action.1 Objective:Study the therapeutical effect of trytanthrin on asthma and investigate its mechanism of action to provide evidence for therapeutical effect of trytanthrin on asthma.2 Methods:2.1 Establish acute asthmatic animal model and compare the asthmatic delitescence of each animal group2.1.1 Establishment and evaluation of acute asthmatic guinea pig model Histamine phosphate aerosol rebreathing method was adopted to establish acute asthmatic cavia cobaya model; animal behavior was observed combing with pathological section to evaluate whether this model was successful duplicated.2.1.2 Analysis the delitescence before and after administrationAfter modeling, medication administration team was intragastric administrated for 1 week, and then asthma was provocated once again. Latent time of asthma was recorded and compared before and after administration to provide evidence whether tryptanthrin has therapeutical effect on asthma.2.2 Establish chronic asthmatic animal model and compare the level of IFN-γ,IL-4,NO,NOS of cavia cobaya in vivo2.2.1 Establishment and evaluation of chronic asthmatic cavia cobaya model Adopt crude egg albumin intraperitoneal injection to sensitize, aerosol rebreathing methods crude egg albumin normal saline solution to activate asthma and establish the model. Animal behavior was observed combing with pathological section to evaluate whether this model was successful duplicated.2.2.2 Detection of NO, NOS, IFN-γand IL-4 levelAdopt nitrate reductase method to detect NO content of serum and BALF, chemical method to detect NOS content of serum, enzyme linked immunosorbent assay (ELISA)to detect IFN-γand IL-4 content of BALF.2.3 Detection of NOS and COX-2 level in lung tissue of chronic asthmatic guinea pigAdopt immunohistochemistry method to dye NOS,COX-2 in lung tissue of guinea pig. After intervention of tryptanthrin and dexamethasone, observe the expression of NOS,COX-2 in lung tissue of guinea pig.3 Results3.1 Compare of delitescenceAsthmatic delitescence after administration(125.8s±16.3s,157.1s±23.6s) was delayed over double times compared with that before administration in tryptanthrin group 70mg/kg and 35mg/kg. Significant deviation(P<0.05)was observed comparing with model group(before administration 58.4s±8.7s, after administration 59.4s±7.4s). The result of pathological section demonstrated that acute mild inflammation in lung was observed in each tryptanthrin group while acute moderate inflammation in lung was observed each model group.3.2 Influence of tryptanthrin on IFN-γand IL-4 level in each group guinea pig in vivoIn serum of guinea pig: The NO contents of tryptanthrin group and dexamethasone group were (66.12±4.86)nmol/L,(70.85±5.32)nmol/L,(74.45±6.03)nmol/L and (65.71±6.01)nmol/L, separately. Significant loss (P<0.05) was observed when compared with modeling group(98.12±10.12)nmol/l. The NOS contents of tryptanthrin group and dexamethasone group were (0.62±0.03)u/ml,(0.67±0.04)u/ml,(0.71±0.05)u/ml,(0.51±0.02)u/ml, separately. Significant loss (P<0.05) was observed when compared with modeling group(0.87±0.05)u/ml.In BALF of cavia cobaya: The NO contents of tryptanthrin group and dexamethasone group were (7.05±2.05)nmol/L,(8.44±2.33)nmol/L,(9.31±2.65)nmol/L,(6.83±1.43)nmol/L, separately. Significant loss (P<0.05) was observed when compared with modeling group (13.57±2.12)nmol/l. The IFN-γlevel of tryptanthrin group and dexamethasone group were(854.94±80.86)pg/ml,(739.08±54.32)pg/ml,(576.45±68.03)pg/ml,(506.71±70.01)pg/ml, separately. Significant loss (P<0.05) was observed when compared with modeling group (423.12±43.34)pg/ml. The IL-4 level of tryptanthrin group and dexamethasone group were ( 9.05±2.39 ) ng/L,(13.14±2.19)ng/L,(19.31±1.45)ng/L,(15.63±1.76)ng/L, separately. Significant increase (P<0.05) was observed when compared with modeling group(43.66±2.27)ng/L.3.3 Tryptanthrin influence on NOS and COX-2 expression in lung of each group guinea pig in vivoDetection on lung tissue of guinea pig demonstrated that NOS expression presented negatively in each intervention group and model group. COX-2 expression presented negatively in each blank and dexamethasone group while COX-2 expression presented positive in each tryptanthrin and model group.4 Conclusions4.1 Tryptanthrin may delay asthmatic attack of guinea pig and relieve inflammation in vivo.4.2 Tryptanthrin may decrease content of NO and NOS.4.3 Tryptanthrin may decrease level of IFN-γand increase that of IL-4 in asthmatic guinea pig. It also can maintain the balance of Th1/Th2.
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