摘要目的：通过观察先天性心脏病性肺动脉高压肺活检组织内肺血管病理学改变及相关蛋白的表达，探讨如何选择和应用评价肺动脉高压可逆性的病理指标。方法收集28例患者的临床资料，包括性别、年龄、先天性心脏病类型、术前平均肺动脉压力（ MPAP）、术后1年MPAP等。对照组选用肺癌患者远离肿瘤的肺组织。根据手术后1年MPAP是否≥25 mmHg（1 mmHg＝0.133 kPa）将患者分为肺动脉高压可逆组和肺动脉高压不可逆组。肺活检组织切片应用肺动脉高压病理学四级分级法进行分级，应用Image-Pro Plus 6.0图像分析系统测量肺小动脉中膜厚度、中膜面积百分比和肺小动脉血管密度，免疫组织化学检测肺内转胶蛋白和细丝蛋白A的表达。结果28例患者中24例为肺动脉压力可逆组，4例为肺动脉压力不可逆组。病理学观察显示28例肺活检中肺血管及肺组织学正常者13名，肺动脉病变Ⅰ级10例，肺动脉病变Ⅱ级3例，肺动脉病变Ⅲ级2例。肺动脉高压可逆组中肺动脉病变0级13例（54.2％，13／24）、Ⅰ级9例（37.5％，9／24））和Ⅱ级2例（8.3％，2／24）。不可逆组中肺动脉病变Ⅰ级者1例（1／4）、Ⅱ级者1例（1／4）和Ⅲ级者2例（2／4）。统计学分析表明，肺动脉高压可逆组术前与术后MPAP均高于不可逆组[（53.3±23.4）mmHg比（34.1±12.7） mmHg，P＝0.020和（35.0±8.8）mmHg比（17.8±3.9）mmHg，P＜0.01]。病理学为肺动脉压力Ⅱ和Ⅲ级者，术前MPAP与肺动脉压力0级和Ⅰ级者比较差异无统计学意义，术后MPAP则显著增高（ P＜0.05或0.01）。肺动脉高压可逆组及不可逆组小动脉中膜厚度百分比和中膜面积百分比与对照组比较显著增加，差异具有统计学意义（P＜0.01），并且不可逆组中膜厚度亦明显高于可逆组（P＝0.001）。通过相关分析表明术前MPAP和术后MPAP与小动脉中膜厚度百分比和中膜面积百分比呈直线相关，而与血管密度无直线相关关系。肺动脉高压是否可逆与肺组织病理学分级无关。转胶蛋白和细丝蛋白A在肺动脉高压不可逆组肺小动脉平滑肌细胞呈强阳性表达，表达强度高于对照组和可逆组（P＜0.05）。结论肺活检组织病理学诊断依然是先天性心脏病合并肺动脉高压判断分级、评估肺动脉高压是否可逆的金标准。定量测量肺小动脉中膜厚度和中膜面积百分比亦有助于评估预后。平滑肌细胞增殖和迁移相关蛋白转胶蛋白和细丝蛋白A可以作为肺动脉高压不可逆性评估的辅助指标。

abstractsObjective To assess the pathologic markers for evaluation of reversibility in pulmonary hypertension ( PAH) related to congenital heart disease .Methods Twenty-eight patients with congenital heart disease complicated by PAH were subclassified into reversible pulmonary hypertension ( RPAH) and irreversible pulmonary hypertension ( IPAH), according to post-operative mean pulmonary artery pressure (MPAP).Pulmonary vascular lesion was analyzed according to Ruan′s method.Mean medium thickness percent, mean medium area percent and pulmonary arteriolar density were measured by quantitative morphometry.Immunohistochemical study for transgelin and filamin A was carried out .Results Amongst the 28 cases studied , 24 were RPAH and 4 were IPAH.Of the 24 patients with RPAH , 13 ( 54.2%, 13/24) had pulmonary vascular lesion of grade 0, 9 (37.5%, 9/24) of grade 1 and 2 (8.3%, 2/24) of grade 2.Of the 4 patients with IPAH, 1 had lesion of grade 1, 1 of grade 2 and 2 of grade 3.Both preoperative and postoperative MPAP were higher in IPAH patients than that in RPAH patients [ ( 53.3 ± 23.4) mmHg versus (34.1 ±12.7) mmHg, P=0.020 and (35.0 ±8.8) mmHg versus (17.8 ±3.9) mmHg, P<0.01].Compared to patients with pulmonary vascular lesion of grades 0 and 1, the preoperative MPAP in patients with grades 2 and 3 showed no significant difference , but the postoperative MPAP was higher (P<0.05 or 0.01).Compared to control group, mean medium thickness percent and mean medium area percent were significantly higher in RPAH and IPAH categories (12.0 ±3.5, 8.5 ±2.0 versus 5.7 ± 1.0, P<0.01 and 55.8 ±11.1, 49.0 ±9.4 versus 34.0 ±5.5, P <0.01 ).Mean medium thickness percent was significantly higher in IPAP group than that in RPAH group (12.0 ±3.5 versus 8.5 ±2.0, P=0.001).Correlation analysis demonstrated that mean medium thickness percent and mean medium area percent had positive correlation with preoperative and postoperative MPAP.There was no correlation between grading of pulmonary vascular lesion and reversibility.Transgelin and filamin A had stronger staining in pulmonary vascular smooth muscle cells in IPAH than those in RPAH and controls (P<0.05).Conclusions Pathologic assessment of lung biopsy remains the gold standard for evaluation of the reversibility in PAH related to congenital heart disease.Mean medium thickness percent , mean medium area percent and immunoreactivity for transgelin and filamin A are useful parameters .