Effect of sildenafil on expression of tumor necrosis factor-alpha in lung tissues of rats with pulmonary hypertension / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of sildenafil on the expression of tumor necrosis factor-alpha (TNF-α) in lung tissues of rats with pulmonary hypertension.Methods Twenty-four male Sprague-Dawley rats,aged 8 weeks,weighing 180-220 g,were randomly divided into 3 groups (n =8 each) using a random number tablecontrol group (group C),pulmonary hypertension group (group PH),and sildenafil group (group S).Sildenafil 50 mg/kg was injected through a gastric tube into stomach once a day for 35 consecutive days starting from 1 day after lelf pneumonectomy in group S.Pulmonary hypertension was induced by left pneumonectomy and subcutaneous monocrotaline injected at 7 days after operation in PH and S groups.At 35 days after operation,mean pulmonary arterial pressure (mPAP),relative medial thickness of pulmonary artery (RMT),right ventricular systolic pressure (RVSP),and muscularization of small pulmonary arteries were measured in the lung.The ratio of the right ventricular weight to the sum of the weights of the left ventricle and septum (RV/(LV + S)) was calculated.The expression of TNF-α mRNA and protein was determined using RT-PCR and Western blot analysis,respectively.Results Compared with group C,mPAP,RVSP,muscularization of small pulmonary arteries,RMT and RV/(LV + S) ratio were significantly increased,and the expression of TNF-α mRNA and protein was upregulated in group PH,and RVSP,muscularization of small pulmonary arteries and RV/(LV + S) ratio were increased in group S.Compared with group PH,mPAP,RVSP,muscularization of small pulmonary arteries,RMT and RV/(LV + S) ratio were significantly decreased,and the expression of TNF-α mRNA and protein was downregulated in group S.Conclusion Sildenafil can down-regulate the expression of TNF-α in lung tissues of rats with pulmonary hypertension,inhibit reconstruction of pulmonary artery,and decrease the pulmonary arterial pressure.