Effect Of Exogenous Hydrogen Sulfide On The Expression Of P38MAPK And FN In Bleomycin-induced Pulmonary Fibrosis In Rats

Objective:Using the bleomycin-induced rats model of pulmonary fibrosis,we observe the expression of p38MAPK and FN in rats with pulmonary fibrosis,and explore the underlying mechanisms of exogenous hydrogen sulfide?s anti-fibrosis in lung.Methods:Sixty 6-week-old healthy male SD rats were choosed and randomly separated into four groups:control group?group A?,bleomycin group?group B?,bleomycin+prednisone acetate group?group C?,bleomycin+sodium hydrosulfide?the H₂S donor?group?group D?.Bleomycin was intratracheally administrated at a dose of 5mg/kg for once making the model of pulmonary fibrosis.But equivalent volume of normal saline was given in group A by the same way.The first day after eastablishing models,rats of groupD were adiministered intraperitoneal injections of NaHS?28?mol/kg?everyday,prednisone acetate?0.56mg/kg?was taked by means of intragastric administration everyday to the rats in groupC.The equal volume of normal saline was administrated by means of intragastric administration in group A and B.5 rats in each group were sacrificed randomly on the day7,14 and 28.The left lung tissue were collected for HE stain and Masson stain and for the expressions of the protein of p38MAPK and FN analysed by means of immunohistochemistry?PV?;The right lung tissue were collected for the expressions of p38MAPK and FN mRNA by means of RT-PCR respectively.Results:1.HE and Massion staining:The lung tissue structure was clear in group A,and the change of inflammatory reaction and fibrosis was not noticeable.The inflammatory reaction in group B was the main manifestations at 7th day,a large number of inflammatory cells infiltrated,the lung tissue structure was broken and alveolar septum began to widened.At 14th day,more lung tissue structure was broken,inflammatory cells are still visible and collagen deposition was aggravated.Finally,at 28th day,the inflammatory reaction was reduced,but a large number of collagen deposition in interstitial lung instead.The pulmonary fibrosis aggravated progressivly at the moment.The inflammatory reaction and fibrosis in group C and D was weakened compared with that in group B,but enhanced than group A.2.p38MAPK,FN mRNA and protein expression?RT-PCR and Immunohistochemistry?:?1?The level of protein of p38MAPK and FN in group A reduced comparedwithgroupB,C,D,thedifferencesabovewere siyiticant?P<0.05?.The level of protein of p38MAPK and FN in group C,D reduced compared with group B,but increased compared with the group A.The differences above were siyiticant?P<0.05?.?2?Compared with group B,C,D the level of mRNA of p38MAPK and FNingroupAreduced,thedifferencesabovewere siyiticant?P<0.05?.Compared with group B,the level of mRNA of p38MAPK and FN in group C,D reduced,but increased compared with the group A.The differences above were siyiticant?P<0.05?.3.Correlation analysis:A positively correlation was existenced between the expression of p38MAPK and FN in the lung tissues of rats with pulmonary fibrosis.?r=0.952,P<0.05?.Conclussions:Exogenous hydrogen sulfide can weaken the degree of pulmonary fibrosis of the bleomycin-induced rats.It's mechanism may be related to block the expression of p38MAPK,therefore reduce the deposition of FN and prevent the excessive accumulation of extracellular matrix?ECM?.