Abstract:Objective:Based on neuregulin/epidermal growth factor receptor(NRG/ErbB) signaling pathways,to discuss the effect of shikonin on rat models with asthma. Methods:A total of 100 SPF Wistar rats were randomly divided into the control group,the model group,the dexamethasone group and the shikonin group of low-dose and high-dose according to their body mass. Rat models with asthma were established in the model group,the dexamethasone group and the shikonin group of low-dose and high-dose,and then were given gastric perfusion correspondingly. The control group and the model group were given saline of corresponding volume. The ratio of wet lung and body mass and partial pressure of oxygen(PaO2) were measured;the lung tissues were sectioned and stained routinely;the lung injury was scored;the expression levels of mRNA and protein of NRG and ErbB in the lung tissues were measured by RT-PCR and immunohistochemistry respectively;the levels of interleukin-2(IL-2),interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in the lung tissues were measured by ELISA method. Results:Compared with those in the control group,the ratio of wet lung and body mass,the score of lung injury, the levels of lymphocyte, eosinophil and neutrophil, the expression levels of mRNA and protein of NRG and ErbB in the lung,and the protein expression levels of IL-2,IL-6 and TNF-α in the model group were significantly increased (P<0.05);the level of PaO2 was significantly decreased(P<0.05). Compared with those in the model group,the ratio of wet lung and body mass,the scores of lung injury,the levels of lymphocyte,eosinophil and neutrophil,the expression levels of mRNA and protein of NRG and ErbB in the lung, and the protein expression levels of IL- 2, IL- 6 and TNF- α in the dexamethasone group and the shikonin group of low-dose and high-dose were significantly decreased(P<0.05);the levels of PaO2 were significantly increased(P<0.05). Compared with the shikonin groud of low-dose,the ratio of wet lung and body mass,the scores of lung injury,the levels of lymphocyte,eosinophil and neutrophil,the expression levels of mRNA and protein of NRG and ErbB in the lung,and the protein expression levels of IL- 2,IL-6 and TNF-α in the shikonin groud of high- dose were decreased(P<0.05),and the level of PaO2 was increased(P<0.05). Compared with those in the dexamethasone group,the ratio of wet lung and body mass,the scores of lung injury,the levels of lymphocyte,eosinophil and neutrophil,the expression levels of mRNA and protein of NRG and ErbB in the lung,and the protein expression levels of IL-2,IL-6 and TNF-α in the shikonin group of low-dose were significantly increased(P<0.05),and the level of PaO2 was significantly decreased(P<0.05). There was no significant difference being found in the comparison of the above indexes between the dexamethasone group and the shikonin group of high- dose(P > 0.05). Conclusion: Shikonin can significantly decrease allergic inflammatory responses in the rat models with asthma, and high- dose shikonin has similar effect to dexamethasone. The mechanism of shikonin is related to its inhibition on the levels of inflammatory factors including IL- 2,IL-6 and TNF-α by inhibiting the expression levels of mRNA and protein of NRG and ErbB.