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Effect Of Exogenous Hydrogen Sulfide On Notch Signaling Pathway In Bleomycin-induced Pulmonary Fibrosis In Rats

Posted on:2020-11-16Degree:MasterType:Thesis
Country:ChinaCandidate:Y X YangFull Text:PDF
GTID:2404330578468129Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
Objective: The goal of this study is to observe the expression of jagged1,hes1,E-cadherin and ?-smooth muscle actin in lung tissue of bleomycin-induced rat pulmonary fibrosis model by exogenous hydrogen sulfide,to explore the effect of notch signaling pathway on pulmonary fibrosis,and further explore the mechanism of action of exogenous hydrogen sulfide on anti-pulmonary fibrosis.Methods: Forty-five adult healthy male SD rats were divided into 3 groups by random number method,with 15 rats in each group,namely group A(blank control group),group B(BLM group),group C(BLM+NaHS group).The group B and C were induced to construct a pulmonary fibrosis model by a single intratracheal instillation of BLM solution(5 mg/kg),and the same volume normal saline was used in group A.From the first day after BLM treatment,group C received intraperitoneal injection of NaHS solution at a dose of 28?mol/kg per day,while group A and group B received daily injection of normal saline of the same volume as group C in the same way.Five rats were randomly selected from each group at each time,and samples were taken at the 7th,14 th and 28 th days after the establishment of bleomycin pulmonary fibrosis model.The left lung tissue was placed in 10% neutral formalin solution for soaking and fixing,and the degree of alveolitis and pulmonary fibrosis was observed by HE and Masson staining.The right lung tissue was used to detect the expression of jagged1,hes1,E-cad and ?-SMA at mRNA and protein levels by RT-qPCR and Western-Blotting detection.Results: 1.HE and Masson staining showed that the lung tissue structure of rats in the blank control group was complete and clear,without obvious alveolitis and pulmonary fibrosis changes.The degree of alveolitis and pulmonary fibrosis of rats in the BLM group was significantly increased,while the degree of alveolitis and pulmonary fibrosis of rats in the BLM+NaHS group was less than that in the BLM group and more than that in the blank control group.2.The results of RT-qPCR showed that the expression of jagged1,hes1 and ?-SMA mRNA in lung tissue of BLM group was significantly higher than that of the blank control group on the 7th,14 th and 28 th day after model establishment,and the expression levels of E-cad mRNA were significantly lower than that of the blank control group at the corresponding time points,the difference was statistically significant(P < 0.05).The expression of jagged1,hes1 and ?-SMA mRNA in the lung tissues of BLM+NaHS group was higher than that of the blank control group at each time point,while the expression of E-cad was lower than that of the blank control group at the corresponding time point,but it was higher than that of the BLM group,the difference was statistically significant(P < 0.05).3.Western-Blotting results showed that the expression of jagged1,hes1 and?-SMA protein in lung tissue of BLM group was significantly higher than that of blank control group on the 7th,14 th and 28 th day after model establishment,and the expression level of E-cad proteins was significantly lower than that of the blank control group at the corresponding time point,and the difference was statistically significant(P < 0.05).The expression of jagged1,hes1 and ?-SMA protein in lung tissue of BLM+NaHS group was higher than that of the blank control group at each time point,the expression level of E-cad protein was lower than that of the blank control group at the corresponding time point,but it was higher than that of the BLM group,the difference was statistically significant(P<0.05).Conclussions: Exogenous hydrogen sulfide can effectively reduce the degree of bleomycin-induced pulmonary fibrosis in rats,which may be through the inhibition of notch signaling pathway activated,thus EMT was inhibited,thereby slowing down the development of pulmonary interstitial fibrosis.
Keywords/Search Tags:Exogenous hydrogen sulfide, Pulmonary fibrosis, Notch signaling pathway, ?-SMA, E-cadherin
PDF Full Text Request
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