生物蛋白胶载体复合加替沙星缓释剂局部应用的实验研究

Local application of fibrin glue carrying gatifloxacin

背景:生物蛋白胶作为生物性抗生素载体,已在临床工作中得到广泛的应用,但生物蛋白胶与第四代氟喹诺酮类广谱抗菌药物加替沙星联合应用的实验研究鲜有报道。目的:拟建立动物局部感染模型,观察生物蛋白胶-加替沙星缓释剂对感染的预防作用及二者联合应用的安全性。方法:新西兰大白兔随机分成3组,均建立局部软组织感染模型,实验组局部放置生物蛋白胶+加替沙星,对照组局部注射加替沙星,空白组局部注射生理盐水。3组动物分别于术前和术后第3,7,14天耳缘静脉采血,进行白细胞计数检查和实验组全血药物浓度测定,同时,分别于术后第3,7,14天各切取切口旁小块肌肉组织,进行组织学检查以及实验组的局部药物浓度测定。结果与结论:空白组动物在术后2周内均出现切口化脓,而对照组和实验组未见切口化脓;白细胞计数结果显示在术后各时间点实验组白细胞计数均低于空白组(P<0.01),而对照组在术后第7和14天白细胞计数显著高于实验组,低于空白组(P<0.01或P<0.05);实验组血浆和距切口约1.5cm处肌肉组织加替沙星的浓度均在给药后3,7,14d逐渐降低(P<0.05);组织学检查结果显示空白组动物肌肉组织中充满大量的炎性细胞,对照组第3,7天时,肌肉组织中有少量炎性细胞,14d时消失,实验组第3天时炎性细胞较少,第7,14天时,无炎性细胞浸润。结果表明,生物蛋白胶是抗感染药物释放系统的良好生物载体,与加替沙星联合应用,可以减少出血,降低感染发生概率。

BACKGROUND： Fibrin glue as a biological carrier of antibiotics, has been widely used in clinical work, but experimental study on fibrin glue in combination with the fourth generation of fluoroquinolone broad-spectrum antibiotic gatifloxacin has been rarely reported. OBJECTIVE： To evaluate the effects of fibrin tissue adhesive and gatifloxacin on preventing and treating local infection of soft tissues after wound and the safety of the local drug delivery system. METHODS： Standard local infection models were established in New Zealand healthy white rabbits, which were grouped randomly into experiment group, control group and blank group. Fibrin tissue adhesive and gatifloxacin were implanted into the local infection site in experiment group, gatifloxacin injected in control group and normal saline injected in blank group. Venous bloods of rabbit ear were collected before the operation and at 3, 7, 14 days after the operation, leukocyte counts of whole blood were determined respectively. The plasma level of gatifloxacin in experiment group was determined. Muscular tissues of lateral incision in experiment group were dislodged at 3, 7, 14 days after the operation to determine the level of gatifloxacin and histological examination. RESULTS AND CONCLUSION： The blank group were infected in two weeks and the incisions were red and edema after the operation; There were no incision pus in experiment group and control group. Leukocyte count at different postoperative time points in experiment group was lower than that in blank group （P 0.01）, the control group was significantly higher than experiment group at 7 and 14 days, lower than blank group （P 0.01 or P 0.05）. The plasma level of gatifloxacin and the level of gatifloxacin of 1.5 cm muscular tissues were gradually reduced at 3, 7, 14 days （P 0.05）; Histological examination revealed there were a lot of inflammatory cells in the muscular tissues of blank group. There were less inflammatory cells in control groups at 3 and 7 days, and no inflammatory cells at 14 days. Less inflammatory cells were found in experiment group at 3 days and no at 7, 14 days. The fibrin tissue adhesive is one kind of good biological carriers in anti-infection drug delivery system, its combination with gatifloxacin can reduce blooding and reduce infection rate.