在粘连形成的大鼠模型中，神经激肽1受体拮抗剂可减少腹腔镜粘连松解术后粘连的重新形成。
A neurokinin 1 receptor antagonist decreases adhesion reformation after laparoscopic lysis of adhesions in a rat model of adhesion formation.
作者信息
Prushik S G, Aarons C B, Matteotti R, Reed K L, Gower A C, Leeman S E, Stucchi A F, Becker J M
机构信息
Department of Surgery, Boston University School of Medicine, 88 East Newton street, C500, Boston, MA 02118, USA.
出版信息
Surg Endosc. 2007 Oct;21(10):1790-5. doi: 10.1007/s00464-007-9248-2. Epub 2007 Mar 14.
BACKGROUND
Up to 94% of patients experience fibrous adhesions after abdominal surgery, and a significant number of these patients require a second operation for open or laparoscopic lysis of adhesions (LOA). The authors have previously shown that inhibition of the binding of tachykinin ligands to the neurokinin 1 receptor (NK-1R) using the neurokinin 1 receptor antagonist (NK-1RA) CJ-12,255 decreases primary adhesion formation and upregulates the peritoneal fibrinolytic system in a rat model. Whereas most studies have focused on the prevention of primary adhesions, few have addressed adhesion reformation after LOA. This study aimed to determine the effects of NK-1RA administration on adhesion reformation and peritoneal fibrinolytic activity after laparoscopic LOA.
METHODS
Adhesions were induced in 31 rats using our previously described ischemic button model. The rats underwent laparoscopy 7 days later, during which adhesions were scored and lysed followed by administration of the NK-1RA or saline. Then 7 days after LOA, 23 rats were killed and adhesions were scored. Eight rats also were killed 24 h after the LOA to obtain peritoneal tissue and fluid, which were analyzed for tissue plasminogen activator (tPA) mRNA expression and peritoneal fibrinolytic activity by reverse transcriptase-polymerase chain reaction (RT-PCR) and bioassay, respectively.
RESULTS
At laparoscopy, 79% +/- 3% of the buttons formed adhesions. In the saline-administered control animals, 42% +/- 3.2% of the buttons reformed adhesions after LOA (p < 0.05), whereas in the animals that received the NK-1RA, 18.2% +/- 3.5% of the buttons reformed adhesions (p < 0.05). As compared with control animals, NK-1RA administration increased tPA mRNA levels by 38% and fibrinolytic activity sixfold (p < 0.05; 7.0 +/- 2.1 U/ml vs 1.2 +/- 0.54 U/ml).
CONCLUSIONS
When administered during laparoscopic LOA, an NK-1RA significantly upregulates peritoneal fibrinolytic activity and decreases adhesion reformation.
背景
高达94%的患者在腹部手术后会出现纤维性粘连，其中相当一部分患者需要进行二次手术以进行开放性或腹腔镜粘连松解术（LOA）。作者之前已经表明，使用神经激肽1受体拮抗剂（NK-1RA）CJ-12,255抑制速激肽配体与神经激肽1受体（NK-1R）的结合，可减少大鼠模型中的原发性粘连形成并上调腹膜纤维蛋白溶解系统。虽然大多数研究都集中在预防原发性粘连上，但很少有研究涉及LOA后的粘连再形成。本研究旨在确定腹腔镜LOA后给予NK-1RA对粘连再形成和腹膜纤维蛋白溶解活性的影响。
方法
使用我们之前描述的缺血纽扣模型在31只大鼠中诱导粘连。7天后，大鼠接受腹腔镜检查，在此期间对粘连进行评分并松解，然后给予NK-1RA或生理盐水。然后在LOA后7天，处死23只大鼠并对粘连进行评分。另外8只大鼠在LOA后24小时也被处死，以获取腹膜组织和液体，分别通过逆转录聚合酶链反应（RT-PCR）和生物测定法分析组织纤溶酶原激活物（tPA）mRNA表达和腹膜纤维蛋白溶解活性。
结果
在腹腔镜检查时，79%±3%的纽扣形成了粘连。在给予生理盐水的对照动物中，42%±3.2%的纽扣在LOA后重新形成粘连（p<0.05），而在接受NK-1RA的动物中，18.2%±3.5%的纽扣重新形成粘连（p<0.05）。与对照动物相比，给予NK-1RA使tPA mRNA水平增加了38%，纤维蛋白溶解活性增加了六倍（p<0.05；7.0±2.1 U/ml对1.2±0.54 U/ml）。
结论
在腹腔镜LOA期间给予NK-1RA可显著上调腹膜纤维蛋白溶解活性并减少粘连再形成。
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