| Aims: To investigate the effects of policosanol on m PAP and remodeling of pulmonary arteries in monocrotaline(MCT)-induced pulmonary arterial hypertension(PAH) rats and its possible mechanisms.Method: Eighty male Sprague-Dawley rats were randomly divided into four groups: normal control group(group NC,20 rats), PAH group(group PAH, 20 rats), policosanol group(group Poli, 20 rats) and atovastatin group(group Ator, 20 rats). Animals received a single intraperitoneal injection of MCT(40mg·kg-1) to induce pulmonary arterial hypertension. The rats in groups(Poli and Ator) were treated with an intragastric administration daily: group Poli(policosanol 10mg·kg-1 ig.) and group Ator(atovastatin 10 mg · kg-1 ig.). The rats in groups(NC and PAH) received equal amount of physiological saline for 4 weeks. The general condition of animals were recorded daily. The mean pulmonary arterial pressure(m PAP) were recorded by Power Lab biological data acquisition system. The heart was harvested to calculate the right ventricular hypertrophy index(RVHI). The ratio of wall/total thickness(WT%) and ratio of wall/total area(WA%) in small pulmonary arteries were determined by HE stain. The apoptosis of endothelial cells in the small pulmonary arteries was detected by TUNEL stain. The expression of apoptotic protein Bax and anti-apoptotic protein Bcl-2 in lung homogenate were detected by Western Blot. The levels of IL-6 and TNF-a were measured by enzyme-linked immunosorbent assay(ELISA).Results:(1) Compared with the rats in group NC, rats in group PAH appeared lazy, dispirited, anorexia, weight loss and even dead. Compared with the rats in group PAH, the general condition was better of animals in group Poli and there was no marked difference between animals in group Poli and Ator.(2) Compared with the rats in group NC, the m PAP and RVHI were higher in group PAH(m PAP: 33.91±4.72 vs 17.57±3.44 mm Hg, p < 0.01; RVHI: 69.25±8.42 vs 24.91±2.82, p < 0.01). Compared with the rats in group PAH, policosanol treatment prevented the increase of m PAP and RVHI(m PAP: 26.94±6.02 vs 33.91±4.72 mm Hg, p < 0.01; RVHI: 55.27±9.89 vs 69.25±8.42, p < 0.05). There was no significant difference in m PAP and RVHI between animals in group Poli and Ator(m PAP: 26.94±6.02 vs 27.41±4.29 mm Hg, p > 0.05; RVHI: 55.27±9.89 vs 53.19±9.94, p > 0.05).(3) Compared with the rats in group NC, the WT% and WA% in small pulnonary arteries were increased in group PAH(WT%: 0.67±0.1 vs 0.32±0.05, p < 0.01; WA%: 0.87±0.05 vs 0.53±0.07, p < 0.01). Compared with the rats in group PAH, the WT% and WA% were decreased of rats in group Poli(WT%: 0.42±0.1 vs 0.67±0.1, p < 0.01; WA%:0.64±0.13 vs 0.87±0.05, p < 0.01). There was no significant difference in WT% and WA% between animals in group Poli and Ator(WT%: 0.42±0.1 vs 0.44±0.06, p > 0.05; WA%: 0.64±0.13 vs 0.67±0.06, p > 0.05).(4) Compared with the rats in group NC, the ratio of apoptotic endothelial cells was increased in group PAH and policosanol treatment protected endothelial cells from apoptosis. Compared with the rats in group NC, the expression of Bax protein and the value of Bax/Bcl-2 in lung were increased(Bax: 1.18±0.11 vs 0.35±0.06,p < 0.01, Bax/Bcl-2: 4.49±1 vs 0.71±0.18, p < 0.01), while Bcl-2 protein was decreased(0.27±0.04 vs 0.5±0.04, p < 0.01) in group PAH. Compared with the rats in group PAH, policosanol therapy inhibited the expression of Bax and decreased value of Bax/Bcl-2(Bax: 0.87±0.04 vs 1.18±0.11, p < 0.01, Bax/Bcl-2: 2.36±0.12 vs 4.49±1,p < 0.01), while promoted the expression of Bcl-2(0.37±0.04 vs 0.27±0.04, p < 0.05). There was no significant difference in the value of Bax /Bcl-2 between animals in group Poli and Ator(2.36±0.12 vs 2.6±0.14,p > 0.05).(5) Compared with the rats in group NC, the levels of IL-6 and TNF-a were increased in rats in group PAH(IL-6: 1750.65±139.17 vs 457.05±49.59 pg/m L, p < 0.01; TNF-a: 276.55±45.35 vs 82.38±6.1 pg/m L, p < 0.01). Compared with the rats in group PAH, the level of IL-6 and TNF-a was decreased in group Poli(IL-6: 1093.06±73.5 vs 1750.65±139.17 pg/m L, p < 0.01; TNF-a: 88.11±8.91 vs 276.55±45.35 pg/m L, p < 0.01). There was no significant difference in the level of IL-6 and TNF-a between animals in group Poli and Ator(IL-6: 1093.06±73.5 vs 1043.83±114.1 pg/m L, p > 0.05; TNF-a: 88.11±8.91 vs 77.1±8.82 pg/m L, p > 0.05).Conclusions: Policosanol exerted beneficial effects in MCT induced PAH and the mechanism of the actions may be related with the inhibition of MCT induced apoptosis and inflammation. |
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