| Objectives:Rats received a single abdominal cavity injection of monocrotaline(MCT), to create the model of pulmonary hypertension. Though detect platelet-derived growth factor B(PDGF-B), interleukin-6(IL-6)and m RNA Rac1 in the lung tissue which is belong to the pulmonary hypertension rats induced by MCT expression. Then further explore the mechanism of pulmonary arterial hypertension(PAH), and to observe the effect and possible mechanism of pitavastatin to preventive this model of PAH.Methods:The models of pulmonary hypertension in rats are created by the inducation of MCT(55mg/kg).Blank control rats were just injected with saline.32 male Sprague-Dawley rats were randomly divided into five groups:blank control group(Blank),model control group(Model),low-dose pitavastatin group(1mg.kg-1.d-1,Pit1p),high-dose pitavastatin group(3mg.kg-1.d-1,Pit3p),prevention control group(1mg.kg-1.d-1,Pit P1p).From the day MCT injection on, rats in Pit P1 p groups were prevented with pitavastatin by daily gavage for 8 weeks.Four weeks after MCT injection,rats in Pit1 p groups and Pit3 p groups were treated with pitavastatin by daily gavage for 4 weeks. From the day MCT injection on, rats in Blank and Model groups just received vehicle by gavage for 8 weeks.Rats’ general state or death were recorded through the whole process.At the end of process,mean pulmonary arterial pressure(m PAP) and right ventricular systolic pressure(RVSP) were measured by using the polygraph system through the right jugular vein.Right ventricular hypertrophy were analysed by right ventricular index[RV/(LV+S)]; Morphological changes of Pulmonary blood vessel were done analysis by HE staining pathology images: percent wall thickness(WT %)= [(medial thickness×2/external diameter)]×100 and percent wall area(WT %)=(wall area / total area) ×100. The level of PDGF-B protein expression in pulmonary artery were assessed by immunohistochemistry. Rac1 m RNA of lung tissue Rac1 were detected by Real-time fluorescent quantitative. IL-6 of lung tissue Rac1 were detected by enzyme-linked immune sorbent assay.Results:1 Survival analysis:At 8th weekend,all rats in Blank groups survived. Survival rates of rats in Pit P1 p, Pit1 p,Pit3p and Model groups were 80%,60%,80% and 40%.Compared with Model groups were significantly different(P<0.05),with statistical significance.2 Haemodynamics and pulmonary vascular morphology:Compared with Blank,Pit P1 p, Pit1 p and Pit3 p groups,Model group rats exhibited higher RVSP,m PAP and right ventricular index( P<0.05),increased wall thickness of small pulmonary artery(P<0.0 5).3 PDGF-B、Rac1 m RNAand IL-6 expression of lung:Compared with PDGF-B expressions of small pulmonary artery,IL-6 expressions of lung tissue and Rac1 m RNA of lung tissue in Blank, Pit P1 p,Pit1p and Pit3 p groups,Model group were significantly higher(P<0.05)Conclusion:1 MCT induced pulmonary artery hypertension and right ventricular hypertrophy in rats. Pitavastatin inhibited smooth muscle cell proliferation, delayed the remodeling of pulmonary vessel,decreased fight ventricular hypertrophy and lowered pulmonary artery hypertension in pulmonary hypertension rats induced with monocrotaline.2 The mechanisms of preventive and therapeutic effects of pitavastatin onmonocrotaline-induced pulmonary arterial hypertension may be inhibition of Rac1,PDGF-B expression,inhibition of smooth muscle cell proliferation,inhibition the perivascular inflammation and the increase of lung IL-6. |
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