BMP4在合并糖尿病的冠状动脉旁路移植术患者原位静脉桥病变中的作用

The Association Between Bone Morphogenic Protein-4 and in-situ Saphenous Vein Graft Pathology in Diabetic Patients Undergoing Coronary Revascularization

中文关键词:  骨形态发生蛋白-4 糖尿病 大隐静脉 冠状动脉旁路移植术

英文关键词:Bone morphogenic protein-4 Diabetes Saphenous vein grafts Coronary artery bypass grafting

中文摘要:

      目的 观察合并糖尿病的冠状动脉旁路移植术(CABG)患者大隐静脉的形态学变化以及骨形态发生蛋白-4(BMP4)在其管壁中的表达与分布情况，初步探讨BMP4在合并糖尿病患者CABG术后静脉桥病变进展中的潜在作用。方法 前瞻性配对纳入2013年1月至2014年12月于我院接受CABG的40例血糖正常患者和40例合并2型糖尿病的患者，并根据糖尿病患者是否需胰岛素治疗分为非胰岛素依赖组(n =24)和胰岛素依赖组(n =16)。应用HE染色测算各组患者静脉桥血管壁的形态学参数，Western blot和免疫组化技术观察BMP4在各组患者静脉管壁中的表达及分布情况。结果 糖尿病患者大隐静脉内膜和中膜增生较非糖尿病患者显著。免疫组化显示BMP4主要表达于静脉中膜平滑肌细胞，而BMP4表达量在糖尿病患者大隐静脉管壁内较非糖尿病患者增高（P <0.05)。糖尿病患者静脉桥中BMP4的表达量与其内膜厚度(r =0.655,P <0.01)、内膜面积(r =0.684, P <0.01)、中膜厚度(r =0.642,P <0.01)、中膜面积(r =0.692,P <0.01）均呈明显正相关。结论 合并糖尿病的CABG患者大隐静脉内膜和中膜增生程度与管壁内BMP4高表达中度相关，而BMP4可能在此类患者静脉桥加速失效进程中发挥了重要的促进作用。以BMP4为靶点的治疗策略是否有助于改善糖尿病患者CABG术后静脉桥通畅率值得深入研究。

英文摘要:

      Objective This study was designed to assess the expression levels of bone morphogenic protein-4 (BMP4) in saphenous veins harvested from diabetic patients undergoing coronary artery bypass grafting (CABG), and to investigate its association with in-situ morphological and pathological changes within the venous wall. Methods From January 2013 to December 2014, forty patients with type 2 diabetes mellitus (DM) and risk factors matched non-DM controls (n =40) were enrolled prospectively. Of the 40 DM patients, 24 had noninsulin-dependent diabetes (NIDM) and the remaining 16 had insulin-dependent diabetes (IDM). Segments of saphenous vein without surgical dilatation from these 80 patients were obtained. Vessel wall characteristics were evaluated by hematoxylin-eosin (HE) staining, and the expression and distribution of BMP4 was assessed by Western blot assay and immunohistochemistry analysis. Results The intimal and medial thickness of the saphenous veins harvested from DM patients were higher than those from non-DM controls. Compared with non-DM patients, the expression level of BMP4 was significantly elevated in diabetic veins (P <0.05), and BMP4 was highly expressed in smooth muscle cells located in the medial layer. Moreover, the expression levels of BMP4 in diabetic veins were significantly correlated with intimal thickness (r =0.655, P <0.01), intimal area (r =0.684, P <0.01), medial thickness (r =0.642, P <0.01) and medial area (r =0.692, P <0.01). Conclusion The pre-existing intimal and medial hyperplasia were significantly correlated with the high expression levels of BMP4 in saphenous veins harvested from diabetic patients, implying a potential role of BMP4 in the progression of vein graft stenotic diseases in this cohort of post-CABG patients. Future studies were warranted in investigating novel therapeutic strategy targeting at BMP4 for improving long-term vein graft patency.