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目的探讨终末期肾病(ESRD)患者冠状动脉旁路移植术(CABG)前大隐静脉桥血管中细胞外基质(ECM)基因表达的特点。方法选择复旦大学附属中山医院自2004年7月至2010年12月期间收治的经冠状动脉造影明确诊断为冠心病患者68例进行研究,将68例患者按术前有无ESRD史,筛选出ESRD患者30例作为ESRD组(需维持性血液透析患者),38例无肾病史患者作为对照组。收集整理所有入选患者详细的术前临床资料;术中收集大隐静脉标本,以基因芯片、免疫组织化学和蛋白印迹法(Western blotting)阐明ESRD条件下CABG术前大隐静脉桥血管中细胞外基质基因表达的情况。结果两组术前临床资料除肾病相关数据外,其余临床资料差异无统计学意义(P>0.05)。ESRD组患者CABG术前大隐静脉桥血管中细胞外基质相关基因表达上调3倍以上的基因有16个,而表达下调3倍以上的基因则有3个;ESRD组基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)活性较对照组升高(2.60±0.50 vs.0.70±0.16,1.80±0.40 vs.0.60±0.15,P<0.01),而组织型基质金属蛋白酶抑制剂-2(TIMP-2)和组织型基质金属蛋白酶抑制剂-3(TIMP-3)活性较对照组降低(0.60±0.19 vs.2.20±0.30,0.90±0.28vs.2.40±0.70,P<0.05)。结论与ESRD相关的多种心血管病危险因素,严重影响CABG术前大隐静脉桥血管中细胞外基质基因表达平衡,并且这种平衡的打破,有促进CABG术后静脉桥血管病变发生的危险。
Objective To investigate the expression of extracellular matrix (ECM) genes in the vessels of the saphenous vein before coronary artery bypass grafting (CABG) in patients with end-stage renal disease (ESRD). Methods 68 cases of coronary heart disease confirmed by coronary angiography admitted to Zhongshan Hospital Affiliated to Fudan University from July 2004 to December 2010 were studied. According to the presence or absence of ESRD before surgery, 68 patients were screened for ESRD Thirty patients were served as ESRD group (maintenance hemodialysis patients), and 38 patients without history of kidney disease served as control group. Collect detailed preoperative clinical data of all the selected patients. Saphenous vein samples were collected during operation. Gene chips, immunohistochemistry and Western blotting were used to clarify the extracellular load Stromal gene expression. Results There was no significant difference in the clinical data between the two groups except the data of nephropathy (P> 0.05). In ESRD group, there were 16 genes up-regulated more than 3-fold in extra-saphenous vein bridge blood vessels before CABG surgery, while 3 genes were down-regulated more than 3 times in ESRD group. The expression of matrix metalloproteinase-2 -2), MMP-9 activity increased (2.60 ± 0.50 vs.0.70 ± 0.16,1.80 ± 0.40 vs.0.60 ± 0.15, P <0.01), whereas tissue-type matrix metalloproteinase TIMP-2 and TIMP-3 were significantly lower than those in control group (0.60 ± 0.19 vs.2.20 ± 0.30, 0.90 ± 0.28 vs. 2.40 ± 0.70, P < 0.05). Conclusions The risk factors of cardiovascular diseases associated with ESRD seriously affect the balance of extracellular matrix gene expression in the vessels of the saphenous vein before CABG surgery and the break of this balance may promote the risk of venous bridging vascular lesions after CABG .