血晶素对缺氧大鼠肺组织PDGF-B基因表达的影响

目的　研究血晶素对大鼠肺组织血小板源性生长因子B链 (PDGF B)基因表达的影响 ,探讨血晶素降低缺氧大鼠右心室收缩压 (RVSP)和改善缺氧性肺血管重构的机制。方法　用右心导管检测RVSP ;以双波长分光光度法测定动脉血中碳氧血红蛋白 (COHb)的含量 ;用免疫组织化学染色观察PDGF B、增殖细胞核抗原 (PCNA)蛋白的表达 ;用原位杂交检测PDGF BmRNA的定位并用图象分析检测其水平。结果　①正常大鼠肺腺泡内动脉 (IAPA)管壁PDGF BmR NA原位杂交及PDGF B、PCNA免疫组织化学染色结果为阴性 ,而缺氧大鼠的上述实验结果均为阳性 ,同时缺氧大鼠动脉血中COHb的含量较正常对照组大鼠高 1 8倍 (P <0 0 1)。②血晶素可使动脉血中COHb含量较单纯缺氧组进一步增多 (P <0 0 5 ) ,抑制缺氧大鼠RVSP的升高 (P <0 0 1) ,肺组织IAPA管壁PDGFmRNA原位杂交及PDGF B、PCNA免疫组织化学染色虽为阳性 ,但弱于单纯缺氧组 ,经图像分析差异有显著性 (P <0 0 1或 0 0 5 )。结论　血晶素促进内源性CO的产生 ,使缺氧大鼠肺组织PDGF B基因表达下调 ,间接地抑制缺氧状态下血管壁平滑肌细胞过度增殖引起的肺血管重构 ,这可能是血晶素改善大鼠缺氧性肺动脉高压的原因之一

Hemin upregulats the expression of the platelet derived growth factor-B gene in the lung of hypoxic rat

AIM To investigate the effect of Hemin on the production of endogenous CO and the expression of PDGF B gene in rat lung tissue, and discuss the mechanism by which Hemin decreases the right ventricular systolic pressure (RVSP) and ameliorated the vascular remodeling of pulmonary artery in the hypoxic pulmonary hypertension rats. METHODS The rat model of hypoxic pulmonary hypertension were recreated by intermittent normal pressure hypoxia (10% O 2). Right ventricular systolic pressure was measured by right ventricular catheter. The quantity of carbon monoxide hemoglobin (COHb) in rat arterial blood was examined by double wavelength spectrophotometry. Expression of PDGF B and PCNA protein were determined by immunohistochemistry staining. PDGF B mRNA was examined by in situ hybridization. RESULTS ① The in situ hybridization and immunohistochemistry staining in the wall of intra acinar pulmonary arteries (IAPA) of normal rats were negative, but positive in hypoxic rats. The quantity of COHb in the arterial blood of hypoxic rats was higher than that of normal rats( P <0 01). ②After treated with Hemin, the quantity of COHb in arterial blood increased( P< 0 05). Compared with the hypoxic rats, the level of PDGF B mRNA and the expression of PDGF B, PCNA proteins were decreased( P <0 01, or P <0 05). CONCLUSION Hemin can induce the production of endogenous CO, and suppress the hypoxic remodeling of pulmonary artery by inhibiting the expression of PDGF B gene.