Effects Of Gemigliptin On The Therapeutic Effect And Inflammatory Factors Of Monocrotaline-induced Pulmonary Arterial Hypertension In Rats

Background Pulmonary hypertension is a pulmonary arterial contraction,pulmonary vascular proliferation and remodeling as the main feature and then lead to progressive increase in pulmonary vascular resistance,eventually leading to right ventricular hypertrophy and failure of pulmonary vascular disease.Its pathogenesis is still unclear,in recent years,many studies have shown that immunoinflammatory factors play an important role in the process of pulmonary hypertension and vascular remodeling,suggesting that it may be a new target for the treatment of pulmonary hypertension DPP4,also known as T cell differentiation antigen CD26,is a 766-amino-acid and highly glycosylated II transmembrane protem that belongs to the family of serine protease,it's one of the catalytic substrate is the intestinal insulin.It is well known that GLP-1 can achieve hypoglycemic effects by stimulating insulin secretion,inhibiting glucagon secretion,delaying gastric emptying and promoting islet ?-cell proliferation,and inhibiting pancreatic ?-cell apoptosis.Studies have shown that GLP-1 and its analogues have anti-inflammatory potential.Dipeptidyl peptidase-IV(DPP4)inhibitors,a major drug for the treatment of type 2 diabetes,Small molecule inhibitors DPP4 exert their effects via inhibition of enzymatic degradation of glucagon—like peptide-1(GLP-1).The widespread expression of DPP4 in tissues such as the vasculature and immune cells suggests that this protein may play a role in cardiovascular function.Recently,more and more studies focus on the pleiotropic effects of DPP4 inhibitors,existing research has shown that it has anti-inflammatory effects.Therefore,we will study the level of inflammatory factors gemigliptin on the treatment of pulmonary hypertension and its impact on inflammatory factors,in order to further seek to cure pulmonary hypertension to provide a theoretical basis.Objective In this study,we believe that the mechanism of pulmonary hypertension involves a variety of inflammatory factors,such as IFN-?,IL-1?,IL-6 and IL-17.Our aim was to observe the therapeutic effect of gemigliptin on pulmonary arterial hypertension in rats and its effect on inflammatory factors in peripheral blood of rats.This study was intended to study gemigliptin,a novel DPP4 inhibitor,to relieve the effect of pulmonary hypertension and its effect on inflammatory factors.Methods Fourty Male SD rats were randomly divided into 3 groups:control group,MCT group and gemigliptin group.The pulmonary hypertension model was established by subcutaneously injection of MCT(60 mg/kg),the intervention group was given gemigliptin[150 mg/(kg·d)]gavage for 28 days.After that,Observation of the general conditions and survival rates between groups of rats,mRVP,RVSP,and RVHI were measured.Immunohistochemistry was used to detect the expression of proliferating cell nuclear antigen(PCNA)and a-smooth muscle actin(a-SMA)in pulmonary artery smooth muscle cells;HE staining was used to assess the Pulmonary vascular remodeling.IL-1??IL-6?IFN-?and IL-17 were measured by ELISA.Results The mPAP,RVSP,RVHI and the remodeling of the small arteries of MCT group were significantly higher than control group(P<0.001).The mPAP,RVSP,RVHI and the remodeling of the small arteries were significantly improved in gemigliptin group compared to MCT group(P<0.001).The expression of a-SMA and PCNA in lung tissue of MCT group was significantly higher than that of control group;The expression of a-SMA and PCNA in lung tissue of gemigliptin group was lower than that of MCT group;The IFN-? level of MCT group were significantly increased than control group(P= 0.009),while gemigliptin group is lower than the MCT group(P= 0.001).The IL-6 level of MCT group were significantly increased than control group(P= 0.039),while gemigliptin group is lower than the MCT group(P=0.005).The IL-1? level of MCT group were significantly increased than control group,while gemigliptin group is lower than the MCT group(P<0.001).The IL-17 level of MCT group were significantly increased than control group(P= 0.004),while gemigliptin group is lower than the MCT group(P= 0.004,P<0.001).Conclusion The results of this study show that gemigliptin may reduce the level of various inflammatory factors,inhibit pulmonary vascular inflammation,reduce pulmonary vascular remodeling and thus reduce the occurrence and development of pulmonary hypertension.