Rapamycin attenuates the development of chronic hypoxia-induced pulmonary hypertension in mice
Background：Pulmonary hypertension (PH) is characterized by a progressive increase in pulmonary vascular resistance, structural remodeling of the pulmonary vasculature, finally, right ventricular failure and death. One trigger of PH is hypoxia which chronically leads to vascular proliferation and remodeling. The proliferation of smooth muscle cells is now recognized to play a significant role in the remodelling of small pulmonary arteries. The mammalian target of rapamycin (mTOR) also known as mechanistic target of rapamycin has been reported to be an important signal pathway which involevd in cell proliferation. However, whether rapamycin could attenuate hypoxia-induced pulmonary hypertension by inhibiting cell proliferation and the possible signal pathways are still unknown.Objective：To investigate the effect of rapamycin on hypoxia-induced pulmonary hypertension andits possible mechanism.Methods：8-week male C57BL/6 mice were exposed to either normobaric hypoxia(10% oxygen) ornormoxic condition (21% oxygen), with or without rapamycin (3mglkg*d, i.p.) orcarboxymethylcellulose as vehicle from the first day. At 0, 1，2, 3 and 4 weeks(6 mice in eachgroup for each time point), The right ventricular pressure(RVSP) of mice was measured by usingclosed-chest cardiac puncture technique, and then, the mice were sacrificed, heart and lung werecollected. The index of right ventricular hypertrophy(RVHI), that is the ratio of the right ventricularweight to left ventricular weight plus the interventricular septum was calculated. Histological andimmunohistochemical measurement were used to assess the distal vascular remodeling.Results：The RVSP and RVHI of control mice were 16.94 1 0.30 mmHg and 0.21810.0047respectively. After 1, 2, 3 and 4 weeks housed in hypoxia, the RVSP gradually increased to19.03士0.69 mmHg (12.64%±5%, p<0.01), 21.22±0.71 mmHg (25.71%±6%, p<0.01), 21.64±0.49 mmHg (28.04%t4%, p<0.01) and 22.27士0.19 mmHg (31.69%±3%, p<0.01) compared with 0 week. TheRVHI gradually raised to 0.2324±0.0034 (6.8%±2.5%, p>0.05), 0.2527±0.0081 (16.49%士6%,p<p.01)，0.3107±0.009 (42.62%±4%, p<0.01), 0.3341±0.0103 (53.52%±5%, p<0.01) comparedwith 0 week.Conclusion： These results suggested that rapamycin could attenuate hypoxia-inducedpulmonary hypertension. But the possible mechanism will be studied furture.
缺氧性高血压 血管重现 雷帕霉素 动物模型
Wang Wang Jun Wang Jie Liu Ran Miao Jing Li Ji-Feng Li Xiao-Min Yu Li-Juan Guo Yuan Lin Chen Wang
epartment of Physiology, Capital Medical University eijing Key Lab of Respiratory and Pulmonary Circ epartment of Physiology, Capital Medical University Beijing Key Lab of Respiratory and Pulmonary Cir
国内会议
2011中华医学会呼吸病学年会暨第十二次全国呼吸病学学术会议
广州
英文
601-602
2011-09-15（万方平台首次上网日期，不代表论文的发表时间）