Department of Anesthesiology, First Affiliated Hospital, China Medical University, 155 Nanjing St, Shenyang, 110001, People's Republic of China.
Clin Exp Med. 2013 Aug;13(3):187-92. doi: 10.1007/s10238-012-0197-2. Epub 2012 Jun 29.
Endotoxin is known to cause acute lung injury (ALI). Here, we investigated the effects and mechanisms of recombinant human bone morphogenetic protein-2 (rhBMP-2) on pulmonary arteriole remodeling in endotoxin-induced ALI in rats. Sixty Wistar rats were randomly divided into 3 groups (n = 20). Control group was infused with normal saline. Lipopolysaccharides (LPS) alone group was infused with LPS. LPS plus rhBMP2 group was infused with rhBMP-2 and LPS. Lung tissue was harvested. The tunica media of the pulmonary arterioles was measured. The expression levels of survivin, p21, cyclin D1, and activated caspase-3 were examined. The proliferation and apoptosis of pulmonary artery smooth muscle cells were evaluated. The tunica media of pulmonary arterioles in LPS alone group was significantly thicker than both that in control and that in LPS plus rhBMP2 groups (P < 0.01). The multiplication rate in LPS alone group was also significantly higher than both that in control and that in LPS plus rhBMP2 groups (P < 0.01). The apoptotic rate in LPS alone group was lower than that in LPS plus rhBMP2 group (P < 0.01). Compared with the control and LPS plus rhBMP2 groups, the expression levels of mRNA and proteins of survivin and cyclin D1 were increased in LPS alone group (P < 0.01), while the expression levels of p21 and activated caspase-3 were decreased (P < 0.01). RhBMP-2 inhibits the remodeling of pulmonary arterioles in endotoxin-induced ALI, which is achieved by enhancing apoptosis and inhibiting proliferation of pulmonary artery smooth muscle cells.
内毒素已知可引起急性肺损伤（ALI）。在这里，我们研究了重组人骨形态发生蛋白-2（rhBMP-2）对大鼠内毒素性 ALI 肺小动脉重塑的影响及其机制。将 60 只 Wistar 大鼠随机分为 3 组（n = 20）。对照组输注生理盐水。脂多糖（LPS）组单独输注 LPS。LPS 加 rhBMP2 组输注 rhBMP-2 和 LPS。采集肺组织。测量肺小动脉中膜。检测存活素、p21、细胞周期蛋白 D1 和活化 caspase-3 的表达水平。评估肺动脉平滑肌细胞的增殖和凋亡。LPS 组的肺小动脉中膜明显比对照组和 LPS 加 rhBMP2 组厚（P < 0.01）。LPS 组的倍增率也明显高于对照组和 LPS 加 rhBMP2 组（P < 0.01）。LPS 组的凋亡率低于 LPS 加 rhBMP2 组（P < 0.01）。与对照组和 LPS 加 rhBMP2 组相比，LPS 组的存活素和细胞周期蛋白 D1 的 mRNA 和蛋白表达水平增加（P < 0.01），而 p21 和活化 caspase-3 的表达水平降低（P < 0.01）。 rhBMP-2 通过增强细胞凋亡和抑制肺动脉平滑肌细胞增殖来抑制内毒素诱导的 ALI 中的肺小动脉重塑。
