标题：内皮抑素联合甘露聚糖肽胸腔灌注对非小细胞肺癌伴恶性胸水患者血清及胸水MMP-9、VEGF的影响

      作者：张洋 1，李小军 2    陕西省核工业二一五医院药学部 1、胸外科 2，陕西 咸阳 712000

      卷次： 2020年31卷3期

      【摘要】 目的 探讨内皮抑素联合甘露聚糖肽胸腔灌注治疗非小细胞肺癌伴恶性胸水对患者血清及胸水基质金属蛋白酶(MMMP-9)、血管内皮生长因子(VEGF)的影响，为临床诊疗提供依据。方法 选取2016年1月至2018年12月在陕西省核工业二一五医院就诊的非小细胞肺癌伴恶性胸水患者98例，采用随机数表法分为观察组和对照组，每组各49例。对照组给予顺铂胸腔灌注治疗，观察组给予内皮抑素+甘露聚糖肽胸腔灌注治疗，均治疗4周。比较两组患者的治疗后临床治疗效果以及治疗前、治疗后的VEGF、MMP-9、免疫球蛋白G (IgG)、免疫球蛋白M (IgM)、免疫球蛋白A (IgA)、肿瘤坏死因子-α (TNF-α)、γ-干扰素(IFN-γ)、白细胞介素-18 (IL-18)水平，并统计治疗期间不良反应发生情况。结果 观察组患者的治疗总有效率为 91.84%，明显高于对照组的 73.47%，差异具有统计学意义(P<0.05)；治疗后，两组患者的VEGF、MMP-9表达水平均降低，观察组分别为(99.23±10.12) pg/mL、(125.23±10.45) ng/mL，明显低于对照组的(112.48±9.95) pg/mL、(136.28±11.89) ng/mL，差异均具有统计学意义(P<0.05)；治疗后，两组患者的免疫球蛋白IgG、IgM、IgA均降低，观察组分别为(2.04±0.56) g/L、(1.88±0.41) g/L、(12.45±2.89) g/L，仍明显高于对照组的(1.78±0.46) g/L、(1.65±0.35) g/L、(10.25±2.54) g/L，差异均具有统计学意义(P<0.05)；。治疗后，两组患者TNF-α、IFN-γ、IL-18均降低，观察组分别为(35.23±5.12) pg/mL、(25.12±4.78) pg/mL、(38.23±4.58) ng/L，明显低于对照组的(45.28±6.02) pg/mL、(29.12±5.02) pg/mL、(46.28±5.02) ng/L，差异均具有统计学意义(P<0.05)；。观察组患者的不良反应总发生率为8.16%，明显低于对照组的22.45%，差异具有统计学意义(P<0.05)。结论 内皮抑素联合甘露聚糖肽治疗非小细胞肺癌伴恶性胸水效果明显，其能抑制VEGF、MMP-9表达，有助于缓解患者炎症状态，减轻免疫功能损害，减少不良反应，值得临床推广使用。
      【关键词】 非小细胞肺癌；恶性胸水；内皮抑素；甘露聚糖肽；基质金属蛋白酶；血管内皮生长因子
      【中图分类号】 R734.2 【文献标识码】 A 【文章编号】 1003—6350（2020）03—0302—04

Effect of intrapleural infusion of endostatin combined with mannan peptide on MMP-9 and vascular endothelialgrowth factor in serum and pleural effusion of patients with non-small cell lung cancer and malignant pleuraleffusion.
ZHANG Yang 1, LI Xiao-jun 2. Faculty of Pharmaceutical Sciences 1, Department of Thoracic Surgery 2, the NuclearIndustry 215 Hospital of Shaanxi Province, Xianyang 712000, Shaanxi, CHINA
【Abstract】 Objective To investigate the effect of intrapleural infusion of endostatin combined with mannanpeptide on matrix metalloproteinase-9 (MMMP-9) and vascular endothelial growth factor (VEGF) in the serum andpleural effusion of patients with non-small cell lung cancer (NSCLC) complicated with nausea hydrothorax, and to pro-vide evidence for clinical diagnosis and treatment. Methods Ninety-eight patients with NSCLC complicating malig-nant pleural effusion from January 2016 to December 2018 were randomly divided into observation group and controlgroup, with 49 patients in each group. The control group was treated with intrapleural infusion of cisplatin, and the obser-vation group was treated with intrapleural infusion of endostatin+mannan peptide. Both were treated for 4 weeks. The clini-cal treatment effect and VEGF, MMP-9, immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA),tumor necrosis factor-α (TNF-α) γ-interferon (IFN-γ), interleukin-18 (IL-18) levels before and after treatment werecompared between the two groups. The occurrence of adverse reactions during treatment was recorded. Results The to-tal effective rate of treatment in the observation group was 91.84%, which was significantly higher than 73.47% in thecontrol group (P<0.05). After treatment, the expression levels of VEGF and MMP-9 in the two groups decreased; thelevels in the observation group were (99.23±10.12) pg/mL, (125.23±10.45) ng/mL, which were significantly lower than(112.48±9.95 ) pg/mL, (136.28±11.89) ng/mL in the control group (P<0.05). After treatment, the immunoglobulin IgG,IgM, and IgA of the two groups were reduced; the levels in the observation group were (2.04±0.56) g/L, (1.88±0.41) g/L,and (12.45±2.89) g/L, which were significantly higher than (1.78±0.46) g/L, (1.65±0.35) g/L, and (10.25±2.54) g/L inthe control group (P<0.05). After treatment, TNF-α, IFN-γ, and IL-18 were reduced in the two groups; the levels in theobservation group were (35.23 ± 5.12) pg/mL, (25.12 ± 4.78) pg/mL, and (38.23 ± 4.58) ng/L, significantly lower than(45.28±6.02) pg/mL, (29.12±5.02) pg/mL, (46.28±5.02) ng/L in the control group (P<0.05). The total incidence of adverse