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Study On The Effect And Its Mechanism Of Ticagrelor In Pulmonary Hypertension

Posted on:2024-08-14Degree:MasterType:Thesis
Country:ChinaCandidate:Y L LiFull Text:PDF
GTID:2544306923974449Subject:Emergency medicine
Abstract/Summary:PDF Full Text Request
Research BackgroundPAH is a highly lethal disease with a poor clinical prognosis due to the lack of effective therapeutic measures.Its pathological mechanism is mainly manifested as the proliferation of pulmonary vascular smooth muscle cells and vascular wall remodeling,and the pulmonary artery pressure is maintained at a high level eventually leading to progressive hypertrophy of the right ventricle.At present,many studies have shown that P2Y receptor family is involved in the proliferation of vascular smooth muscle cells in pulmonary hypertension.However,whether Ticagrelor,as a P2Y12 receptor inhibitor,is also associated with the generation of pulmonary hypertension has not been reported.PurposeThis study was conducted to construct a rat model of MCT-induced PAH and observe the changes of pulmonary artery vascular remodeling indexes after the intervention with the P2Y12 receptor inhibitor Tegretol to investigate the effects of Tegretol on the progression of PAH and its possible molecular mechanisms.Research MethodsEighty SD rats were randomly divided into four groups:①normal control group(Sh group:N=20);②normal+Tegretol group(Sh+T group:N=20):Tegretol(14mg/kg)was given subcutaneously once daily and observed for 4 weeks;③MCT-induced PAH group(PAH group:N=20):MCT(60mg/kg)was given once after partial excision of left lung tissue for 1 week of adaptation;④MCT-induced PAH+Tegretol group(PAH+T group:N=20):After partial excision of the left lung tissue for 1 week,MCT 60mg/kg was given once subcutaneously,while Tegretol 14mg/kg was given subcutaneously once daily and observed for 4 weeks.After 4 weeks of experiment,observation of hemodynamics,RVSP,right ventricular pressure curve and right ventricular wall thickness were performed in four groups of SD rats;then four groups of animals were executed,and samples were taken for histopathological observation(HE staining,immunohistochemistry,immunofluorescence,etc.);and the protein expression of α-SMA and P2Y12 receptors were observed by Western blotting method.Results1.After 28 days of MCT induction,the RVSP,right ventricular pressure profile,and right ventricular wall thickness of rats in the MCT-induced PAH group were significantly higher than those in the Sh group,and the differences were statistically significant(P<0.05).2.Pulmonary artery pressure and vessel wall thickness were significantly increased in the PAH group of SD rats;pulmonary artery pressure and vessel wall thickness were decreased in the PAH+T group compared with the PAH group,and the differences were statistically significant.3.The protein expression of α-SMA and P2Y12 receptors was significantly higher in the PAH group and lower in the PAH+T group compared with the Sh group as revealed by Western blotting and immunofluorescence,and the differences were statistically significant.4.In the MCT-induced PAH rat animal model,the results of HE staining showed a significant thickening of pulmonary vascular intima SMC and a significant increase in right ventricular systolic pressure in the PAH group;the thickening of pulmonary vascular intima SMC was reduced significantly in the PAH+T group,and the right ventricular systolic pressure was increased first and then decreased.ConclusionPulmonary artery SMC value added in MCT-induced PAH rats was significantly reduced after Tegretol intervention,and right ventricular systolic pressure was increased and then decreased,suggesting that Tegretol may improve pulmonary hypertension through inhibition of the P2Y12 receptor pathway.
Keywords/Search Tags:Ticagrelor, pulmonary artery hypertension,PAH, P2Y12 receptor, smooth muscle cell proliferation, monocrotaline,MCT, pulmonary artery remodeling
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