腺病毒介导的人组织型纤溶酶原激活剂过表达可预防大鼠腹膜粘连的形成/再形成。
Adenovirus-mediated overexpression of human tissue plasminogen activator prevents peritoneal adhesion formation/reformation in rats.
作者信息
Atta Hussein M, Al-Hendy Ayman, El-Rehany Mahmoud A, Dewerchin Mieke, Abdel Raheim Salama R, Abdel Ghany Hend, Fouad Rasha
机构信息
Department of Surgery, Faculty of Medicine, Minia University, El-Minia, Egypt.
出版信息
Surgery. 2009 Jul;146(1):12-7. doi: 10.1016/j.surg.2009.02.018.
BACKGROUND
Tissue-plasminogen activator (tPA) demonstrated beneficial effects on peritoneal adhesion formation; however, its short half-life limits its continual fibrinolytic effect. Therefore, we delivered adenovirus encoding tPA to prevent adhesions.
METHODS
Rats were subjected to peritoneal injury and assigned to two protocols. In de novo adhesion protocol, adenovirus encoding human tPA gene (Ad-htPA) was instilled after peritoneal injury in group 1 (n = 22), whereas group 2 received phosphate-buffered saline (PBS) (n = 24). In recurrent adhesion protocol, group 1 (n = 15) received the same Ad-htPA dose after adhesiolysis and group 2 (n = 13) received PBS. Adhesion severity was scored 1 week after ad-htPA instillation. Adhesions were analyzed for htPA mRNA by reverse transcription-polymerase chain reaction and levels of htPA, and fibrinolytic inhibitors PAI-1, TIMP-1, and TGF-beta1 were measured using enzyme-linked immunosorbent assay.
RESULTS
htPA mRNA and protein were only expressed in adhesions from treated groups. A reduction in adhesion scores (P < .01) and in fibrinolytic inhibitors (P < .001) occurred in the treatment groups. Also, negative correlation was found (r = -.69, P < .01) between adhesion scores and htPA protein, but a positive correlation was found (r = .90, P < .01) between adhesion score and fibrinolytic inhibitors. No bleeding or wound complications were encountered.
CONCLUSION
Administration of adenovector encoding htPA is safe and decreased de novo and recurrent peritoneal adhesions.
背景
组织型纤溶酶原激活剂（tPA）对腹膜粘连形成具有有益作用；然而，其短半衰期限制了其持续的纤溶作用。因此，我们递送编码tPA的腺病毒以预防粘连。
方法
将大鼠造成腹膜损伤并分为两个方案组。在新生粘连方案中，第1组（n = 22）在腹膜损伤后滴注编码人tPA基因的腺病毒（Ad-htPA），而第2组接受磷酸盐缓冲盐水（PBS）（n = 24）。在复发性粘连方案中，第1组（n = 15）在粘连松解术后接受相同剂量的Ad-htPA，第2组（n = 13）接受PBS。在滴注Ad-htPA后1周对粘连严重程度进行评分。通过逆转录-聚合酶链反应分析粘连组织中的htPA mRNA，并用酶联免疫吸附测定法测量htPA水平以及纤溶抑制剂PAI-1、TIMP-1和TGF-β1的水平。
结果
htPA mRNA和蛋白仅在治疗组的粘连组织中表达。治疗组的粘连评分（P <.01）和纤溶抑制剂水平（P <.001）降低。此外，粘连评分与htPA蛋白之间呈负相关（r = -.69，P <.01），但粘连评分与纤溶抑制剂之间呈正相关（r =.90，P <.01）。未遇到出血或伤口并发症。
结论
给予编码htPA的腺载体是安全的，可减少新生和复发性腹膜粘连。
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