Abstract:

To investigate changes and functions of nuclear factor κB (NF κB) and its inhibitor PDTC in monocrotaline（MCT）induced pulmonary arterial hypertension（PAH）. MethodsPulmonary arterial hypertension rat models were established by injecting MCT toxin. A total of 58 Wistar rats were randomly divided into 7 groups : the MCT0 group, the MCT1W group, the MCT2W group, the MCT3W group, the control/vehicle group, the MCT/ vehicle group, and the MCT/PDTC group. Hemodynamic studies were determined by right cardiac catheterization, activity of NFκB was determined by EMSA, and expression of intercellular adhesion molecule1 (ICAM1) and macrophage infiltration were determined by immunohistochemistry. ResultsICAM1 expression and macrophage infiltration were significantly upregulated from week 1 after injection(P<0.01), and the mean  right ventricular pressure and indexes of right ventricular hypertrophy increased from week 2 after injection(P<0.01). Compared with controls, MCT treatment increased the mean  right ventricular pressure (27.8±1.5?mmHg  vs 17.2±1.4?mmHg, P<0.01), which was reduced by PDTC treatment(18.4±2.2?mmHg, P<0.01). Indexes of right ventricular hypertrophy induced by MCT were similarly inhibited (P<0.01) by PDTC treatment, which was associated with suppression of ICAM1 expression and macrophage infiltration. ConclusionWe conclude that NFκB activity and ICAM1 expression are probably associated with the development of MCTinduced PAH, which is ameliorated by administering a NFκB inhibitor, PDTC.

Key words: Pulmonary arterial hypertension; Nuclear factorκB; Nuclear factorκB inhibitor; Intercellular adhesion molecule1; Inflammation; Rats, Wistar