St. Joseph Translational Research Institute, St. Joseph Hospital of Atlanta, Atlanta, GA, USA,
Dig Dis Sci. 2014 Sep;59(9):2118-25. doi: 10.1007/s10620-014-3139-x. Epub 2014 Apr 8.
Intraperitoneal adenosine reduces abdominal adhesions. However, because of the ultra-short half-life and low solubility of adenosine, optimal efficacy requires multiple dosing.
Here, we compared the ability of potential adenosine prodrugs to inhibit post-surgical abdominal adhesions after a single intraperitoneal dose.
Abdominal adhesions were induced in mice using an electric toothbrush to damage the cecum. Also, 20 μL of 95 % ethanol was applied to the cecum to cause chemically induced injury. After injury, mice received intraperitoneally either saline (n = 18) or near-solubility limit of adenosine (23 mmol/L; n = 12); 5'-adenosine monophosphate (75 mmol/L; n = 11); 3'-adenosine monophosphate (75 mmol/L; n = 12); 2'-adenosine monophosphate (75 mmol/L; n = 12); 3',5'-cyclic adenosine monophosphate (75 mmol/L; n = 19); or 2',3'-cyclic adenosine monophosphate (75 mmol/L; n = 20). After 2 weeks, adhesion formation was scored by an observer blinded to the treatments. In a second study, intraperitoneal adenosine levels were measured using tandem mass spectrometry for 3 h after instillation of 2',3'-cyclic adenosine monophosphate (75 mmol/L) into the abdomen.
The order of efficacy for attenuating adhesion formation was: 2',3'-cyclic adenosine monophosphate > 3',5'-cyclic adenosine monophosphate ≈ adenosine > 5'-adenosine monophosphate ≈ 3'-adenosine monophosphate ≈ 2'-adenosine monophosphate. The groups were compared using a one-factor analysis of variance, and the overall p value for differences between groups was p < 0.000001. Intraperitoneal administration of 2',3'-cAMP yielded pharmacologically relevant levels of adenosine in the abdominal cavity for >3 h.
Administration of 2',3'-cyclic adenosine monophosphate into the surgical field is a unique, convenient and effective method of preventing post-surgical adhesions by acting as an adenosine prodrug.
腹腔内给予腺苷可减少腹部粘连。然而，由于腺苷的超短半衰期和低溶解度，为了达到最佳疗效需要多次给药。
本研究比较了潜在的腺苷前体药物在单次腹腔内给药后抑制术后腹部粘连的能力。
使用电动牙刷损伤盲肠诱导小鼠腹部粘连；此外，将 20 μL 95%乙醇应用于盲肠以造成化学诱导损伤。损伤后，小鼠腹腔内分别给予生理盐水（n=18）或接近溶解度极限的腺苷（23 mmol/L；n=12）；5'-单磷酸腺苷（75 mmol/L；n=11）；3'-单磷酸腺苷（75 mmol/L；n=12）；2'-单磷酸腺苷（75 mmol/L；n=12）；3'，5'-环单磷酸腺苷（75 mmol/L；n=19）；或 2'，3'-环单磷酸腺苷（75 mmol/L；n=20）。2 周后，观察者对治疗方法进行盲法评分。在第二项研究中，使用串联质谱法测量了腹腔内给予 2'，3'-环单磷酸腺苷（75 mmol/L）后 3 h 内的腹腔内腺苷水平。
减轻粘连形成的疗效顺序为：2'，3'-环单磷酸腺苷>3'，5'-环单磷酸腺苷≈腺苷>5'-单磷酸腺苷≈3'-单磷酸腺苷≈2'-单磷酸腺苷。采用单因素方差分析比较各组，组间总体 p 值<0.000001。腹腔内给予 2'，3'-cAMP 可在腹腔内产生>3 h 的具有药理相关性的腺苷水平。
将 2'，3'-环单磷酸腺苷施用于手术部位是一种独特、方便、有效的方法，可通过作为腺苷前体药物来预防术后粘连。
