Effects Of Sulforafan Activated NRF2/ARE Pathway On Pulmonary Fibrosis Induced By Bleomycin In Rats

Objective:AIM To investigate the effect and mechanism of sulforafan on pulmonary fibrosis induced by bleomycin.Methods:Forty-five male SD rats were randomly divided into control group(groupN),model group(group B),and sulforafan group(groupS)with 15 rats in each group.The rats in the model group and sulforafan group were slow intratracheally injected with bleomycin and physiological saline mixture solution 0.2-0.3 mL(5mg·kg-1),and the rats in the control group were injected with the same volume physiological saline solution.The day after the operation,the rats in the sulforafan group received intraperitoneal injection of sulforafan solution 5 mg·kg-1,while the rats in the control group and model group were injected with equal volume of physiological saline solution every other days.After the drug intervention in each group,five rats were randomly sacrificed at the day 7,day 14 and day 28.Samples were collected to determine malondialdehyde(MDA)content and the activity of superoxide dismutase(SOD)in serum,and hydroxyproline(HYP)content in lung tissue.HE and Masson staining were performed to evaluate the pathological changes of lung tissue.The expression of nuclear factor E2 related factor 2(Nrf2),heme oxygenase 1(HO-1)protein and mRNA were determined by Western blot and qRT-PCR.Results:At each time point,the Szapiel score of HE staining、Masson staining,HYP content of lung tissue and serum MDA level in the model group were higher than those in the control group and sulforafan group(P<0.01).The SOD activity in the model group was lower than that in the control group(P<0.01),while the SODactivity in the sulforafan group was higher than that in the model group(P<0.05 or P<0.01).The expression of Nrf2,HO-1 protein and mRNA in the model group were higher than those in the control group(P<0.01),while the expressions in the sulforafan group were higher than those in the model group(P<0.05 or P<0.01).Conclusion : Sulforafan play an important role in delaying the occurrence and development of pulmonary fibrosis in rats,which may be related to the inhibition of oxidative stress through Nrf2/ARE pathway activation.