目的 检测分化抑制因子1（Id-1）在肝细胞肝癌组织中和正常肝组织中的表达情况，了解Id-1与肝细胞肝癌患者预后关系。 方法 对获得的19例肝细胞肝癌组织标本和8例正常肝组织进行免疫组织化学染色，并对染色结果进行分级。借助SPSS软件，分析肝细胞肝癌组织标本与正常肝组织标本中的Id-1表达强度区别，Id-1与甲胎蛋白（AFP）相关性，及Id-1表达强度与肝癌患者预后之间的关系。 结果 免疫组织化学染色结果显示所有标本均表达为阳性，其中3例（+），7例（++），10例（+++）7例（++++），肝细胞肝癌组织标本与正常肝组织标本差异有统计学意义（P＜0.05）；Id-1表达与血液中AFP水平相关不显著（r=−0.121，P=0.621）；Spearman等级相关分析显示患者生存时间与Id-1表达呈负相关（r=−0.567，P=0.011）。 结论 Id-1在肝癌组织中表达增高 ，Id-1表达水平与生存时间呈负相关，但和AFP无明显相关。
ObjectiveTo explore the possibility that GREM1, a bone morphogenetic protein (BMP) antagonist, is a mechanical explanation for BMP signal suppression in congenital heart disease associated pulmonary arterial hypertension (CHD/PAH) patients.MethodsSystemic-to-pulmonary shunt induced PAH was surgically established in rats. At the postoperative 12th week, right heart catheterization and echocardiography evaluation were performed to evaluate hemodynamic indexes and morphology of right heart system. Right heart hypotrophy index and pulmonary vascular remodeling were evaluated. Changes of BMP signal pathway related proteins and GREM1 in lungs and plasma GREM1 concentration were detected. The effect of GREM1 on the proliferation and apoptosis of pulmonary arterial endothelial cells (PAECs) was also explored.ResultsThe hypertensive status was successfully reproduced in rats with systemic-to-pulmonary shunt model. BMP signal pathway was suppressed but GREM1 was up-regulated with no change in hypoxia inducible factor-1 in lungs exposed to systemic-to-pulmonary shunt, while this trend was reversed by systemic-to-pulmonary shunt correction (P<0.05). Immunohistochemical staining demonstrated enhanced staining of GREM1 in remodeled pulmonary arteries. In vitro experiments found that BMP signal was down-regulated but GREM1 expression and secretion were up-regulated in proliferative PAECs (P<0.05). Furthermore, BMP2 significantly inhibited PAECs proliferation and promoted PAECs apoptosis (P<0.05), which could be antagonized by GREM1. In addition, plasma level of GREM1 in rats with systemic-to-pulmonary shunt was also increased and positively correlated with pulmonary hemodynamic indexes.ConclusionSystemic-to-pulmonary shunt induces the up-regulation of GREM1 in lungs, which promotes pulmonary vascular remodeling via antagonizing BMP cascade. These results present a new mechanical explanation for BMP pathway suppression in lungs of CHD/PAH patients.