| Background and Objective PAH is the progressive increase of pulmonary vascular resistance characterized with obstructive lesions of pulmonary vasculature and hyperplasia of pulmonary arteries, finally leading to right heart failure and death. PAH is mainly caused by body-lung diffluent abnormal hemodynamics due to abnormal anatomical structure. Clinically, it usually erupts simultaneously with patients suffering from congenital heart disease. With the progression of the disease, it is getting more difficult for clinical treatment, leading to quite high fatality rate. In recent years, the targeted therapy aimed at various links of PAH pathogenesis has been widely applied such as NO inhalation therapy, phosphodiesterase inhibitor, prostacyclin drug, endothelin receptor antagonist, ACER drug, ARB drug, calcium ion antagonist, etc. So far, there haven’t been drugs with obvious effect in treating PAH resulted from abnormal hemodynamic. Pulmonary vasoconstriction, the formation of micro thrombus in pulmonary vascular and pulmonary reconstruction (smooth muscle cell and endothelial cell hyperplasia, change of inflammation ground substance) are deemed as three significant pathophysiological basis, among which inflammatory response with participation of such inflammatory cytokines as IL-1, IL-6, TNF-a and NF-κB has played critical role in formation and development process of PAH. As a safe and stable pyruvic acid derivative, ethyl pyruvate has been verified to have effective effects free radical injury resistance, anti-inflammatory, anti-septicopyemia immunoregulation and organ protection, etc. Ethyl pyruvate can restrain NF-κB activity, reduce cell factors (TNF-a, IL-1β, IL-8, etc.), adhesion molecule and chemotactic factor through changing the oxidation environment in the cell, further mitigating inflammatory response for the purpose of anti-inflammatory. Therefore, we can deduct that it is of great significance for treatment of hyperdynamic PAH by interdicting development and progression of inflammatory response from the source with ethyl pyruvate. To evaluate the effect of EP on hyperkinetic pulmonary arterial hypertension (PAH).Method We established the rat hyperkinetic PAH model by the shunt of common carotid artery and internal jugular vein in the method of common carotid artery-internal jugular vein casing. Thirty hyperkinetic PAH rats were randomly divided into 3 groups with 10 rats in each group:EP treatment group, control group and shunt group. Another 10 rats treated with vessel separation but not casing surgery are taken randomly as the sham-operation group for negative control. The rats in EP treatment group were given intraperitoneal injection of EP (50mg/kg/day) for 30 days, and the rats in control group were injected with the same volume of normal saline. The systolic pulmonary arterial pressure (SPAP) was measured after injection for 30 days and then the right ventricular hypertrophy index (RVHI) was calculated after killing the rats by exsanguinations and removing their heart and lung. The percentage of diameter thickness (WT%) and wall area (WA%) were calculated through HE staining lung tissues. The levels of TNF-a and IL-6 in the serum were measured by ELISA and the expression of NF-κB p65 in lung tissues was detected by Western blot.Result Compared with shunt group, SPAP and RVHI in treatment group decreased obviously; WT% and WA% showed thinner wall of pulmonary artery and better narrow lumen. ELISA results showed the levels of IL-6 and TNF-a in serum in treatment group decreased obviously, which was of statistical significance (P<0.05). Western blot results showed the expression of NF-κB p65 in lung tissues in treatment group decreased significantly, which was of statistical significance (P<0.05).Conclusion EP could ameliorate PAH and inhibit the remodeling of pulmonary blood vessels in hyperkinetic PAH rats through reducing the expression of NF-kB p65, the synthesis and release of cytokines (TNF-a, IL-6, etc.) and alleviate inflammation reaction. |
PDF Full Text Request