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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。
Objective To observe the morphological changes of saphenous vein and the expression and distribution of bone morphogenetic protein-4 (BMP4) in the wall of coronary artery bypass grafting (CABG) patients with diabetes mellitus (DM). To investigate the expression of BMP4 in patients with diabetes mellitus Potential role of CABG in the development of venous bridge lesions. Methods Forty patients with CABG in our hospital from January 2013 to December 2014 were prospectively matched and 40 patients with type 2 diabetes mellitus were divided into two groups according to whether insulin therapy is required or not: n = 24) and insulin dependent group (n = 16). HE staining was used to measure the morphological parameters of venous graft in each group. Western blot and immunohistochemistry were used to observe the expression and distribution of BMP4 in the venous wall of each group. Results The intima and media of the great saphenous vein in patients with diabetes mellitus were significantly higher than those in non-diabetic patients. Immunohistochemistry showed that BMP4 was mainly expressed in VSMCs, while BMP4 expression was significantly increased in non-diabetic patients (P <0.05). The expression of BMP4 in venous bridge of diabetic patients was positively correlated with the thickness of intima (r = 0.655, P <0.01), intima area (r = 0.684, P <0.01) Membrane area (r = 0.692, P <0.01) showed a significant positive correlation. Conclusions The degree of intimal and mesangial hyperplasia of saphenous vein in patients with diabetes mellitus is moderately correlated with the high expression of BMP4 in the wall of the vessel, while BMP4 may play an important role in accelerating the failure of venous bridge in these patients. Whether BMP4 as a target therapeutic strategy can help improve the rate of venous graft patency after CABG in diabetic patients deserves further study.