Effect Of Treprostinil On Expression Of Inhibitor Of Dna Binding In Rat Model With Pulmonary Arterial Hypertension

Objective: Establishment of a rat model of pulmonary hypertension induced by monocrotaline,exploration of the therapeutical effect of treprostinil on PAH and investigation of the relationship between Inhibitor 1,3 of DNA binding(Id1,Id3)and PAH.Method:(1)30 rats were randomly divided into 3 groups: normal saline control group,monocrotaline model group,and treprostinil intervention group.The model group and intervention group rats were injected with monocrotaline,and the control group were given same amount of saline.After 3 weeks by injection of Monocrotaline,the intervention group was treated for 2 weeks with treprostinil,the other two groups were given same amount of saline.After 5 weeks,the general situation and body quality in the each group rats were observed.(2)The mean right ventricular pressure(mRVP),pulmonary arterial systolic pressure(PASP),right ventricular hypertrophy index(RVHI),the percentages of wall thickness of pulmonary arteriole to external diameter of artery(WT%)and vascular wall area to total vascular area(WA%)were determined to reflect the index of PAH.(3)By making lung tissue pathological slices,detect the Id1 and Id3 protein expression level in lung tissue were detected by immunohistochemical method.(4)By Western blotting and q-PCR technique to detect the expressions level of Id1 and Id3 protein and the Id1 mRNA and Id3 mRNA to observe there relations with PAH.(5)Statistical analysis: the data were analyzed with SPSS 17.0(statistical package for social science).Measurement data were described with(_x ± s).Means among multiple groups were compared by One-Way Analysis(Analysis of variance).Means between two groups were compared by 2-independent-Samples T Test,and P<0.05 was considered statistically significant.Result:(1)The activities,diet decreased more significantly,the response was slower,the colour became less luster in the monocrotaline model group and treprostinil intervention group than those of the saline control group;The body quality decreased more significantly in the monocrotaline model group compared with the saline control group(P < 0.05);there was no statistical significance in the body quality between the treprostinil intervention group and the treprostinil intervention group(P > 0.05).(2)The mRVP,PASP,RVHI,WT% and WA% in model group were significantly higher than those in control group(P<0.05),the intervention group were lower than the model group(P<0.05)in mRVP,PASP,RVHI,WT% and WA%.(3)The expression of level of Id1,Id3 protein,detected by immunohistochemical method,in lung tissue and pulmonary vascular in monocrotaline model group were apparently lower than those of the saline control group(P < 0.05);while the level of Id1,Id3 protein in lung tissue and pulmonary vascular in the intervention group were apparently higher than those of the monocrotaline model group(P < 0.05).(4)The level of Id1,Id3 protein and Id1 mRNA,Id3 mRNA in monocrotaline model group were apparently lower than those of the saline control group(P < 0.05),while the level of Id1,Id3 protein and Id1 mRNA,Id3 mRNA in the intervention group were apparently higher than those of the monocrotaline model group(P < 0.05).Conclusion: Treprostinil has therapeutic effect on rats with pulmonary hypertension;the therapeutical effect on the pulmonary hypertension maybe associated with the changes of expression level of Id1,Id3 and Id1 mRNA,Id3mRNA.