Effects Of Atorvastatin On Monocrotaline-induced Pulmonary Hypertension And Lung NF-κB Expression In Rats

Objective: To investigate the effects of atorvastatin onmonocrotaline (MCT)-induced pulmonary hypertension in rats and theexpression of nuclear factor-kappa B (NF-κB) in lung.Methods: Twenty-four male SD rats were randomly divided intothree groups with eight rats each group: control group, MCT group andatorvastatin group (AS group). The rats in MCT and AS group were givena single subcutaneously injection of MCT (60mg/kg) and the rats incontrol group were injected with saline. Atorvastatin (10mg/kg/d) weregiven orally for 21 days to the rats in AS groups and vehicle were givento the rats in MCT group since the day when rats were injected MCT. At22 days, mean pulmonary arterial pressure (mPAP), mean carotidpressure (mCAP) and right ventricular hypertrophy index (RVHI) weremeasured. The index of wall thickness of pulmonary arteriole wasmeasured by a computerized image analyzer. The expression of NF-κB inbronchioles was observed by immunohistochemistry.Results:1. The mPAP and RVHI were increased significantly in MCT groupthan that in control group (P＜0.01). This increase in mPAP and RVHI was partially prevented by atorvastatin(P＜0.01). There was no significantdiscrepancy on mCAP between three groups (P＞0.05).2. The thickness of the medial wall of pulmonary medial arteries andarteriole was significantly increased in MCT group as compared withcontrol group. Large numbers inflammatory cells congregated around thesmall vascular and in the pulmonary interstitial in MCT group.Atorvastatin treatment was associated with a significant reduction ofMCT-induced thickening and the number of inflammatory cells.3. WT％and WA％of pulmonary medial arteries and arteriole wereincreased significantly in MCT group than that in control group (P＜0.01).This increase in WT％and WA％was partially prevented by atorvastatin(P＜0.01).4. The percentage of positive cells for NF-κB nuclear staining inbronchiolar epithelial cells was significantly increased in MCT groupthan that in the control group (P＜0.01), but in AS group, it wassignificantly decreased than that in the MCT group(P＜0.01).5. The percentage of positive cells for NF-κB nuclear staining inbronchiolar epithelial cells was positively correlated with mPAP andWT％and WA％of pulmonary medial arteries and arteriole(P＜0.01,respectively).Conclusions: Atorvastatin could reduce NF-κB expression ofbronchiolar induced by MCT, prevent MCT-induced inflammatory response, pulmonary vascular remodeling and the development ofpulmonary hypertension.