Effect Of Pae On Inflammatory Mediators Of PASMCs

Pulmonary hypertension is a complex disease with pulmonary vascular remodeling as its main pathological change.Its early manifestation is usually inflammatory reaction.With the change of hemodynamics,the physical strength of patients with pulmonary hypertension will decline sharply,and angina pectoris and dyspnea will occur.More serious,right heart failure will occur and lead to death.Paeonol is an active ingredient extracted from Ranunculaceae plant Paeonia lactiflora,Peony and Cynanchum paniculata.Paeonol has the functions of antipyretic,analgesic,anti-inflammatory and protecting cardiovascular system.In recent years,many researchers have found that paeonol can inhibit the release of inflammatory mediators in vascular tissue.Therefore,the focus of this study is whether paeonol can alleviate and improve the pulmonary inflammatory response caused by pulmonary hypertension by inhibiting the release of pulmonary inflammatory mediators,thereby alleviating the symptoms of pulmonary hypertension,and providing new ideas and methods for the treatment of pulmonary hypertension.The hypoxic environment was created by hypoxic chamber in order to establish pulmonary hypertension rat model.Intercellular adhesion factor-1(ICAF-1),interleukin-6(IL-6)and vascular cell adhesion factor-1(VCAF-1),which are important mediators of inflammation,were selected as indicators of inflammatory mediators.The right heart catheterization and hematoxylin-eosin staining were used to check whether the model was successful.Immunohistochemical technique was used to observe the changes of pulmonary vascular morphology in rats and to understand the effect of Paeonol on inflammatory infiltration.Protein imprinting method was used to detect the levels of ICAF-1,IL-6 and vascular cell adhesion factor-1 in lung tissue of three groups of SD male rats to understand the effect of Paeonol on the expression of inflammatory mediators.Rat pulmonary artery smooth muscle cells were cultured in vitro.The expression of ICAF-1,IL-6,ICAF-1 and other inflammatory mediators in rat pulmonary artery smooth muscle cells was detected by real-time quantitative PCR and Western blotting at different hypoxia time and concentration gradients.The effects of paeonol with different concentration gradients on the proliferation of rat pulmonary artery smooth muscle cells under hypoxic environment were studied by thiazole blue colorimetry in vitro.Finally,real-time quantitative PCR and Western blotting were used to detect the expression of inflammatory mediator adhesion factor-1,interleukin-6 and vascular cell adhesion factor-1 in pulmonary artery smooth muscle cells of rats in five groups:nonnoxia,hypoxia,adding inhibitors,adding paeonol,adding inhibitors and paeonol at the same time.The activation of p38 pathway in five groups.To study the effect of Paeonol on these inflammatory mediators in rat pulmonary artery smooth muscle cells through p38 pathway.Through the analysis of the experimental results,it was found that paeonol could inhibit or even reverse the pathological changes of pulmonary artery wall thickening and vascular stenosis caused by hypoxia.It can significantly improve the right ventricular systolic pressure and inflammatory infiltration induced by hypoxia,and reduce the expression of inflammatory mediators such as Intermediate Adhesion Factor-1,Interleukin-6 and Vascular Cell Adhesion Factor-1 in lung tissue.It was also found that in hypoxic environment,the levels of inflammatory mediators such as ICAF-1,IL-6 and ICAF-1 in pulmonary artery smooth muscle cells were positively correlated with hypoxic time,and reached the highest level after 24 hours of hypoxia.The effect was dose-dependent.When the concentration of paeonol was 120 mmol L-1,the effect was the best.When p38 inhibitor,paeonol and p38 inhibitor+paeonol were added to cultured rat pulmonary artery vascular smooth muscle cells in vitro,it was found that the expression trend of inflammatory mediators such as ICAF-1,IL-6 and ICAF-1 was the same,and the p38 inhibitor had synergistic effect with paeonol.In conclusion,we can conclude that paeonol has an inflammatory response to pulmonary tissue.It has a good inhibitory effect and can alleviate the pulmonary hypertension response.And this effect is achieved through the p3 8 pathway.