| Objective:This study aims to observe the effect of exogenous hydrogen sulfide（H2S）on the pathological changes of lung tissue and the expression of notch1 and jagged1 protein and mRNA in pulmonary tissue of rats with bleomycin-induced pulmonary fibrosis,to explore the role of notch signaling pathway in pulmonary fibrosis and the possible mechanism of exogenous H2S against pulmonary fibrosis.Methods:120 female Sprague-Dawley rats were selected and divided into blank control group（group A）,bleomycin model group（group B）,BLM+prednisone acetate group（group C）,BLM+sodium hydrosulfide group（Group D）,30 rats in each group.The rats in groups B,C and D were injected intratracheally with BLM（5mg/kg）to establish the model of pulmonary fibrosis,and group A was injected with the same volume of saline.On day 1 after modeling,group C received intragastric administration of 0.56 mg/kg/d of prednisone acetate at 8:00 am every day,and group D received daily intraperitoneal injection of 28μmol/kg NaHS solution.Groups A and B received the same volume of physiological saline as group D by intraperitoneal injection.On the 7th,14 th and 28 th days,three batches were taken and 10 rats were randomly selected from each group,The left lung tissue of rats was soaked in 10%neutral formalin for fixation of pathological specimens（HE,Masson staining）,Right lung tissue was used to detect notch1,jagged1 mRNA expression by RT-PCR.Results:1.The results of HE and Masson staining showed that there was no obvious pathological changes in the lung tissue of the blank control group,but the pulmonary alveolitis degree and the degree of fibrosis in the bleomycin model group were significantly aggravated.Sodium hydrogen sulfide intervention group and prednisone acetate In the intervention group,alveolitis and fibrosis in the lung tissue were lighter than those in the model group,but still more severe than those in the blank control group.2.The results of immunohistochemistry showed that the expression of notch1 and jagged1 protein in the lung tissue of the blank control group was only slightly expressed in the alveolar epithelial cells on the 7th,14 th and 28 th days.The expression of notch1 protein in the lung tissue of the model group was high at the corresponding time points（P<0.05）.The expression of notch1 protein in BLM+prednisone acetate group and BLM+sodium hydrosulfide group was lower than that in model group at each time point,but higher than that in blank control group,The difference was statistically significant（P<0.05）.3.RT-PCR results showed that the expression level of notch1 mRNA in lung tissue of model group was significantly increased on the 7th,14 th and 28 th day respectively compared with the blank control group（P<0.05）.The BLM+prednisone acetate group and The expression of notch1 mRNA in BLM+sodium hydrosulfide group was lower than that in model group at each time point,but higher than that in blank control group,the difference was statistically significant（P<0.05）.Conclussions:Exogenous hydrogen sulfide can reduce the degree of pulmonary fibrosis in rats with bleomycin-induced pulmonary fibrosis,which may be related to its inhibition of notch1,jagged1 expression in notch signaling pathway. |
