摘要
目的:研究ERK信号通路在大鼠低氧高二氧化碳性肺动脉高压发生发展中的动态变化;探讨三七总皂苷(PNS)防治低氧高二氧化碳性肺动脉高压的机制。方法:复制慢性低氧高二氧化碳性肺动脉高压大鼠模型;分为正常(N)组,低氧高二氧化碳性肺动脉高压3 d(H3d)、1周(H1w)、2周(H2w)、4周(H4w)组及PNS治疗(Hp)组,Hp组腹腔注射三七总皂甙注射液,余组注射等量生理盐水;光镜下比较各组大鼠肺细小动脉结构;West-ern印迹法和免疫组织化学技术检测各组肺组织及肺血管p-ERK、ERK蛋白的表达。结果:(1)H1w、H2w、H4w和Hp组的肺细小动脉管壁面积/管总面积(WA/TA)均高于N组(均P<0.05),但H3d组较N组增加不明显(P>0.05),Hp组WA/TA明显低于H4w组(P<0.05)。(2)肺组织p-ERK蛋白在N组表达不明显,在H3d组表达即开始上升,在H1w、H2w、H4w组均高水平表达(P<0.05)。(3)肺小动脉壁p-ERK蛋白在N组表达呈弱阳性或阴性,H3d组表达上升,在H1w、H2w、H4w组表达水平逐渐升高(P<0.05)。(4)Hp组肺组织p-ERK蛋白、肺小动脉壁p-ERK蛋白表达较低氧高二氧化碳组降低(P<0.05)。结论:ERK信号通路可能介导了大鼠低氧高二氧化碳性肺动脉高压的形成。PNS可能通过抑制p-ERK表达减轻这一过程。
AIM： To investigate the roles of Panax notoginoside（PNS） and ERK1/2 signaling pathway in the pathological process of chronic hypoxic hypercapnia pulmonary hypertension in rats.METHODS： The animal model of chronic hypoxic hypercapnia pulmonary hypertension was set up in 72 male Sprague-Dawley rats and the animals were randomly divided into 6 groups： normal（N） group,hypoxic hypercapnia for 3-day（H3d） group,hypoxic hypercapnia for 1-week（H1w） group,hypoxic hypercapnia for 2-week（H2w） group,hypoxic hypercapnia for 4-week（H4w） group and PNS treatment （Hp） group.The rats in Hp group were injected with PNS（50 mg·kg-1·d-1,ip） before placing the animals into the hypoxic hypercapnia chamber.The rats in other groups were injected with normal saline（2 mL/kg,ip）.The morphological changes of the pulmonary artery were observed under microscope with HE staining.Western blotting was used to detect the protein expression of p-ERK. The protein levels of p-ERK in the lung tissues and pulmonary blood vessels were determined by immunohistochemistry.RESULTS： The ratios of WA/TA in H1w,H2w,H4w and Hp groups were higher than that in N group（P0.05）.The ratio of WA/TA in Hp group was obviously lower than that in H4w group（P0.05）.The protein expression of p-ERK was barely positive in N group,but was up-regulated in the pulmonary tissues in all hypoxic rats.Compared with N group,the protein level of p-ERK was markedly up-regulated in H3d group,reached its peak in H2w group,and tended to decline in H4w group（P0.05）.In pulmonary arterial tunica intima and tunica media,p-ERK protein was dramatically expressed in all hypoxic rats compared with the control animals（P0.05）.In the lung tissues, the protein level of p-ERK in Hp group was lower than that in H4w group（P0.05）.In pulmonary arterial tunica intima and tunica media,the protein level of p-ERK in Hp group was lower by 84.86% than that in H4w group （P0.05）.CONCLUSION： ERK1/2 as a signal transducer may play an important rol
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2011年第9期1796-1801,共6页
Chinese Journal of Pathophysiology
基金
浙江省科技攻关资助项目(No.2006C33073)
