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目的探讨骨髓增殖性肿瘤(myeloproliferative neoplasms,MPN)患者血清血管调控相关细胞因子水平及其临床意义。方法 30例MPN患者为MPN组,20例体检健康者为对照组,2组采用双抗体夹心ELISA法检测血清血管内皮生长因子(vascular endothelial growth factor,VEGF)、血小板衍生生长因子(platelet derived growth factor,PDGF)、内皮抑素(endostatin,ES)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)及基质金属蛋白酶抑制剂-1(tissue inhibitors of metalloproteinase-1,TIMP-1)水平,分析MPN组各血管调控细胞因子间的相关性,及临床因素与血管调控细胞因子间的关系。结果MPN组血清VEGF[(610.10±295.70)ng/L]、PDGF[(9.50±3.68)μg/L]、ES[(6.80±2.70)μg/L]、MMP-9[(856.32±544.28)μg/L]、TIMP-1[(464.45±216.71)μg/L]水平及MMP-9/TIMP-1比值(2.41±1.77)均高于对照组[(355.82±155.29)ng/L、(6.03±1.07)μg/L、(4.04±0.90)μg/L、(382.90±171.36)μg/L、(202.37±28.35)μg/L、1.88±0.71](P<0.05);MPN组VEGF与PDGF呈正相关(r=0.429,P=0.018),PDGF与ES呈正相关(r=0.418,P=0.022);MPN组白细胞计数≥10×109/L者血清MMP-9水平[(1 059.95±625.22)μg/L]明显高于<10×109/L者[(623.60±316.93)μg/L](P<0.05),血红蛋白≥160g/L者血清TIMP-1水平[(385.66±178.38)μg/L]明显低于<160g/L者[(554.49±227.31)μg/L](P<0.05),≥60岁患者血清PDGF[(10.70±4.14)μg/L]、ES[(7.93±2.85)μg/L]、TIMP-1[(533.89±200.88)μg/L]水平高于<60岁患者[(7.71±1.83)μg/L、(5.10±1.19)μg/L、(360.29±204.25)μg/L](P<0.05),>2项血管危险因素者血清PDGF水平[(14.01±4.99)μg/L]明显高于≤2项危险因素者[(8.38±2.45)μg/L](P<0.05);多因素logistic回归分析结果显示,高龄和低血红蛋白是TIMP-1水平增高的独立危险因素(OR=1.005,95%CI:1.000~1.010,P=0.049;OR=0.996,95%CI:0.992~1.000,P=0.046);高龄和>2项血管危险因素是PDGF水平增高的独立危险因素(OR=1.462,95%CI:1.008~2.119,P=0.045;OR=1.282,95%CI:0.988~1.663,P=0.041)。结论 MPN患者白细胞计数、血红蛋白增多与血管新生调控因子表达增加有关,通过炎症导致血管新生促进和抑制因子的表达失衡,进而参与MPN的发生、发展。
Objective To investigate the serum levels of vascular related cytokines and their clinical significance in patients with myeloproliferative neoplasms (MPN). Methods Thirty MPN patients were divided into MPN group and 20 healthy subjects as control group. The levels of serum vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), endostatin (ES), matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase-1 (TIMP- To investigate the correlation between MPN-mediated cytokines and the relationship between clinical factors and vascular regulatory cytokines. Results The levels of serum VEGF [(610.10 ± 295.70) ng / L], PDGF [(9.50 ± 3.68) μg / L], ES [(6.80 ± 2.70) μg / L], MMP-9 [(856.32 ± 544.28) /L]TIMP-1[464.45 ± 216.71μg / L] and the ratio of MMP-9 / TIMP-1 (2.41 ± 1.77) were higher than those in the control group [(355.82 ± 155.29) ng / L, 1.07), (4.04 ± 0.90) μg / L, (382.90 ± 171.36) μg / L, (202.37 ± 28.35) μg / L, 1.88 ± 0.71] (r = 0.429, P = 0.018). There was a positive correlation between PDGF and ES (r = 0.418, P = 0.022). The level of serum MMP-9 in MPN group with white blood cell count ≥10 × 109 / L [(1 059.95 ± 625.22) (P <0.05). The serum levels of TIMP-1 in patients with hemoglobin≥160g / L [(385.66 ± 178.38) μg / L] were significantly higher than those in patients with <10 × 109 / L (P <0.05). The serum levels of PDGF in ES group (P <0.05) were lower than <160g / L [(554.49 ± 227.31) μg / L] ], TIMP-1 [(533.89 ± 200.88) μg / L] were significantly higher in patients younger than 60 years (7.71 ± 1.83 μg / L, 5.10 ± 1.19 μg / L, 360.29 ± 204.25 μg / L, (P <0.05). Serum levels of PDGF> (14.01 ± 4.99) μg / L for> 2 vascular risk factors were significantly higher than those of ≤2 (8.38 ± 2.45) μg / L .05). Multivariate logistic regression analysis showed that both age and low hemoglobin were independent risk factors of TIMP-1 (OR = 1.005, 95% CI: 1.000 ~ 1.010, P = 0.049; OR = 0.996, 95% CI : 0.992-1.000, P = 0.046). The elderly and> 2 vascular risk factors were independent risk factors of PDGF (OR = 1.462,95% CI: 1.008-2.1119, P = 0.045; OR = 1.282, 95% CI : 0.988 ~ 1.663, P = 0.041). Conclusions The white blood cell count and hemoglobin in patients with MPN are related to the increased expression of angiogenesis regulatory factors. Inflammation leads to the imbalance between the promotion of angiogenesis and the expression of inhibitory factors, and then to the occurrence and development of MPN.