5-羟基癸酸盐对低氧大鼠肺动脉平滑肌细胞转化生长因子β_1表达的抑制作用  

Inhibitory effect of 5-hydroxydecanoate on transforming growth factor-beta 1 expression in pulmonary artery smooth muscle cells in hypoxic rats

作　　者：朱海萍[1] 董莉[2] 李玉苹[2] 叶君如[2] 黄晓颖[2] 胡红玲[2] 陈成水[2] 

机构地区：[1]温州医学院附属第一医院重症监护室,浙江温州325000 [2]温州医学院附属第一医院呼吸科,浙江温州325000

出　　处：《中国药理学与毒理学杂志》2012年第4期510-514,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：浙江省自然科学基金重点项目(Z208100)~~

摘　　要：目的探讨5-羟基癸酸盐(5-HD)降低低氧性肺动脉高压的作用机制。方法雄性SD大鼠每天(10.0±0.5)%O2处理8 h,连续7 d后,sc给予5-HD 5 mg·kg-1后再进行同样的低氧处理,每天1次,连续21 d。测定右心室肥厚指数(RVHI),右心导管法测肺动脉平均压(mPAP);分别用ELISA法检测肺组织、免疫组化法检测肺动脉和支气管上皮中转化生长因子β1(TGF-β1)的表达。结果与正常对照组比较,低氧模型组的mPAP,RVHI及TGF-β1在肺动脉及支气管上皮细胞中的表达均明显升高(P<0.05),TGF-β1在肺组织中表达无明显升高。与低氧模型组相比,5-HD 5 mg·kg-1组肺动脉平滑肌mPAP和TGF-β1表达明显下降(P<0.05);但RVHI及TGF-β1在肺组织及支气管上皮细胞中的表达无明显变化。结论 5-HD可能是通过TGF-β1信号通路发挥抗肺动脉平滑肌细胞的增殖作用而减轻肺动脉高压。OBJECTIVE To explore the effect and mechanism of 5-hydroxydecanoate （5HD） on hypoxic pulmonary artery hypertension. METHODS Adult male SD rats were exposed tohypoxia with O2（10.0 ±0.5）% for 8 h, once daily, for7 d, and then sc given 5-HD 5 mg·kg^-l, once a day, for 21 d. The right ventricular hypertrophy index（RVHI） and mean pulmonary artery pressure （mPAP） were measured by right cardiac catheter. Expression of transforming growth factor β1 （TGF-β1） in lung tissue was tested by enzyme linked immunosorbent assay（ELISA） while TGF-β1 expression in the pulmonary artery and bronchial epithelial cells was detected by immunohistochemical staining assay. RESULTS Compared with normal control group, mPAP, RVHI and TGF-β1 in puhnonary artery and bronchial epithelial cells in hypoxic group were significantly increased （ P 〈 0.05 ）, but there was no significant difference in TGF-131 expression in lung tissue. Compared with hypoxic model group, mPAP and TGF-β1 expression in the smooth muscle of the pulmonary artery in 5-HD group were significantly decreased （ P 〈 0.05 ）. However, there was no significant difference in RVHI and TGF-β1 expression in lung tissue and bronchial epithelial cells. CONCLUSION 5-HD could reduce pulmonary hypertension mediated by TGF-β1 signaling pathways, which has antiproliferation effect on the smooth muscle cells of the pulmonary artery.

关 键 词：线粒体ATP敏感性钾通道 转化生长因子 肺动脉高压 

分 类 号：R543.2[医药卫生—心血管疾病]