负压封闭引流联合前列地尔促进糖尿病足溃疡创面愈合的疗效和机制研究

目的探讨负压封闭引流联合前列地尔促进糖尿病足溃疡创面愈合的疗效及机制。 方法将广州市第一人民医院烧伤科2017年1月至2018年12月收治的43例采用负压封闭引流进行治疗的糖尿病足溃疡患者按随机数字表法分为观察组(n＝23)和对照组(n＝20)，2组患者均进行负压封闭引流治疗，在此基础上观察组联合静脉滴注前列地尔。治疗前及治疗第7、14天，分别采集2组患者晨空腹静脉血3 mL；治疗第7、14天，采集患者引流袋中引流液5 mL，离心取上清液，移入已消毒的Eppendorf管中，密封，冻存于－80 ℃低温冰箱，并于患者更换负压材料时取部分肉芽组织，10%甲醛固定，石蜡切片。分别检测观察组及对照组患者治疗前，治疗第7、14天血液中降钙素原和血清白蛋白含量及治疗第7、14天引流液中的一氧化氮、血管内皮生长因子(VEGF)、肉芽组织晚期糖基化终末产物受体(RAGE)及腐胺含量，数据比较采用t检验和χ²检验。 结果治疗前2组患者降钙素原和血清白蛋白含量比较差异无统计学意义(P值均大于0.05)；治疗第7、14天，观察组降钙素原分别为(0.61±0.46)、(0.30±0.28) ng/mL，低于对照组(0.93±0.47)、(0.49±0.29) ng/mL，差异均有统计学意义(t＝－2.21、－2.15，P＝0.03、0.04)；观察组血清白蛋白(27.13±2.13)、(28.78±1.90) g/L]，高于对照组(25.48±2.66)、(25.48±2.66) g/L]，差异均有统计学意义(t＝2.17、3.18，P＝0.04、<0.01)。观察组治疗第7、14天引流液中一氧化氮含量分别为(86.30±5.82)、(106.97±6.44) μmol/L，浓度高于对照组(65.64±5.76)、(84.80±9.19) μmol/L]，差异均有统计学意义(t＝11.67、9.25，P值均小于0.01)；VEGF含量分别为(123.04±11.76)、(240.15±38.85) pg/mL，浓度高于对照组(85.09±6.72)、(129.57±17.28) pg/mL]，差异均有统计学意义(t＝12.72、11.74，P值均小于0.01)；观察组治疗第7、14天，引流液中腐胺浓度为(0.63±0.08)、(0.22±0.08)mg/L，低于对照组(0.81±0.09)、(0.41±0.08)mg/L]，差异均有统计学意义(t＝－6.74、－12.15，P值均小于0.01)；取材的肉芽组织中RAGE为37.1±6.76、17.17±5.54，表达低于对照组(52.94±8.72、38.00±5.69)，差异均有统计学意义(t＝－6.90、－7.95，P值均小于0.05)；观察组治疗的总有效率为95.70%，对照组为60.00%，比较差异有统计学意义(χ²＝9.00，P＝0.029)。 结论负压封闭引流联合前列地尔可以促进糖尿病足溃疡创面愈合，其机制与前列地尔促进血管内皮分泌一氧化氮、VEGF，加速创面腐胺清除，促进创面肉芽生长的同时抑制RAGE表达有关。

Study on the effect and mechanism of alprostadil in promoting wound healing of diabetic foot ulcer

ObjectiveTo investigate the effect and mechanism of vacuum sealing drainage combined with alprostadil in promoting wound healing of diabetic foot ulcer. MethodsFourty three patients with diabetic foot ulcer treated with vacuum sealing drainage from January 2017 to December 2018 in the Department of Burns, Guangzhou First People′s Hospital were divided into observation group (n=23) and control group (n=20) according to the random number table method. Both groups were treated with vacuum sealing drainage, and the observation group combined with intravenous infusion of alprostadil. Before and on the 7th and 14th day of treatment, 3 mL of morning fasting venous blood was collected from the two groups of patients. On the 7th and 14th day of treatment, 5 mL of drainage fluid from the patient′s drainage bag was collected, the supernatant was centrifuged, and transferred to the sterilized Eppendorf tube and sealed, frozen in -80 ℃ low-temperature refrigerator. When the patients changed the negative pressure material, some granulation tissue was taken, fixed with 10% formaldehyde, and the paraffin sections was made. The levels of procalcitonin and serum albumin in the blood of the observation group and the control group were detected before, on the 7th and 14th day of treatment. The nitric oxide and vascular endothelial growth factor (VEGF) in the drainage fluid on the 7th and 14th day of treatment, and the granulation tissue receptor for advanced glycation end products (RAGE) and putrescine content were detected. Data were compared with t test and χ² test. ResultsThere was no significant difference in the content of procalcitonin and serum albumin between the two groups before treatment (with P values above 0.05). On the 7th and 14th day of treatment, the procalcitonin in the observation group was (0.61±0.46) and (0.30±0.28) ng/mL, lower than those in the control group (0.93±0.47) and (0.49±0.29) ng/mL], the differences were statistically significant (t=-2.21, -2.15; P=0.03, 0.04). The serum albumin was (27.13±2.13) and (28.78±1.90) g/L in the observation group, which were significantly higher than those in the control group (25.48±2.66) and (25.48±2.66) g/L], the differences were statistically significant (t=2.17, 3.18; P=0.04, <0.01). The content of nitric oxide in the drainage fluid of the observation group on the 7th and 14th day of treatment was (86.30±5.82), (106.97±6.44) μmol/L, and the concentrations were higher than those in the control group (65.64±5.76), (84.80±9.19) μmol/L], the differences were statistically significant (t=11.67, 9.25; with P values below 0.05); the content of VEGF was (123.04±11.76) and (240.15±38.85) pg/mL, respectively, the concentration were higher than those of the control group (85.09±6.72) and (129.57±17.28) pg/mL], the differences were statistically significant (t=12.72, 11.74; with P values below 0.05). On the 7th and 14th day of treatment in the observation group, the putrescine concentration in the drainage solution was (0.63±0.08) and (0.22±0.08) mg/L, which were lower than those of the control group (0.81±0.09) and (0.41±0.08) mg/L], the differences were statistically significant (t=-6.74, -12.15; with P values below 0.05). RAGE in the granulation tissues taken were 37.1±6.76, 17.17±5.54, and the expression were lower than those of the control group 52.94±8.72, 38.00±5.69, the differences were statistical significance (t=-6.90, -7.95; with P values below 0.05); the total effective rate was 95.70% in the observation group and 60.00% in the control group, the difference was statistically significant (χ²=9.00, P=0.029). ConclusionVacuum sealing drainage combined with alprostadil can promote wound healing of diabetic foot uler and the mechanism is related to alprostadil promoting endothelial secretion of nitric oxide and VEGF, accelerating the removal of putrescine, promoting wound granulation growth and inhibiting RAGE expression.