生长因子介导5-HD在肺动脉高压中的抗增生作用

5-hydroxydecanoate Mediated by Growth-factor on Hypoxia Pulmonary Hypertension by Anti-proliferation

目的研究mitoKATP抑制剂5-HD对在体动物低氧性肺动脉高压和各生长因子表达的变化,探讨5-HD是否通过某生长因子的信号通路介导抗肺动脉平滑肌细胞增生的机制。方法雄性SD大鼠24只,随机分为3组:A组:常氧组;B组:低氧组;C组:低氧+5-HD组。右心导管法测肺动脉平均压,ELISA和免疫组化法检测PDGF,VEGF,TGF-β1,EGF的表达。结果①低氧组mPAP较正常、低氧+5-HD组均有明显升高,有统计学差异(P<0.01,P<0.05)。低氧的RVHI较正常组明显升高,有统计学差异(P<0.05),但与低氧+5-HD组间无统计学差异(P>0.05);②ELISA结果表明EGF在低氧、低氧+5-HD组中较正常组均有明显升高,有统计学差异(P<0.05)。但低氧与低氧+5-HD组间无明显统计学差异(P>0.05)。低氧时PDGF、VEGF、TGF-β1虽较正常组有升高,但无统计学差异(P>0.05);③免疫组化示低氧时肺动脉上TGF-β1▲,EGF,PDGF较正常组均有明显升高,有统计学差异(P<0.01▲,P<0.05),且在肺动脉平滑肌层表达明显。其中TGF-β1在低氧+5-HD组明显下降,与低氧组间有明显统计学差异(P<0.05),与正常组间无明显差异(P>0.05)。结论低氧时TGF-β1表达明显上调,参与了肺动脉高压的形成,而mitoKATP拮抗剂5-HD可能通过减少TGF-β1的表达发挥抗肺动脉平滑肌细胞的增生,降低肺动脉高压。

ObjectiveTo study the mechanism that 5-hydroxydecanoate（5-HD） mediated by growth factor in pulmonary arterial smooth muscle cell anti-proliferation.Methods24 healthy adult male SD rats were randomly divided into three groups： A for nomal group; B for hypoxia group; C for hypoxia ＋mitoKATP inhibitor （5-HD） group. Using immunohistochemical staining and ELISA assay,we measured the expression of PDGF, VEGF, EGF, TGF-β1 in lung tissue. Results①Hypoxic group′s mPAP was significantly increased, with significant difference （P〈0.01） than that of the normal group. The hypoxia ＋5-HD group′s mPAP was decreased significantly （P〈0.05）. ②ELISA results showed that the expression of EGF in hypoxic and hypoxia ＋5-HD group rats was significantly higher than the normal group （P〈0.05）. However, hypoxia group and hypoxia ＋5-HD groups had no significant difference （P〉005）. ③Immunohistochemistry showed that the expression of the TGF-β1▲, EGF and PDGF was located on pulmonary artery smooth muscle layer,and their expression in hypoxia was significantly higher than in normal group,with a significant difference between the normal group（P〈0.01▲,P〈0.05）.While the expression of TGF-β1 in hypoxia ＋5-HD group was significantly decreased with significant difference as compared with the hypoxia group （P〈0.05）, with no significant difference between the normal group （P〉0.05）.Conclusion5-HD enables the expression of TGF-β1 in hypoxia group significantly decreased, suggesting that 5-HD might be mediated by TGF-β1 signaling transduction pathways in pulmonary vascular remodeling.