Ben Shahar Yoav, Sukhotnik Igor, Bitterman Nir, Pollak Yulia, Bejar Jacob, Chepurov Dmitriy, Coran Arnold, Bitterman Arie
Department of Surgery, Carmel Medical Center, Haifa, Israel.
Department of Pediatric Surgery, Bnai Zion Medical Center, Haifa, Israel.
Eur J Pediatr Surg. 2016 Feb;26(1):47-53. doi: 10.1055/s-0035-1559886. Epub 2015 Sep 17.
N-acetylserotonin (NAS) is a naturally occurring chemical intermediate in the biosynthesis of melatonin. Extensive studies in various experimental models have established that treatment with NAS significantly protects heart and kidney injury from ischemia-reperfusion (IR). The purpose of the present study was to examine the effect of NAS on intestinal recovery and enterocyte turnover after intestinal IR injury in rats.
Male Sprague-Dawley rats were divided into four experimental groups: (1) Sham rats underwent laparotomy, (2) sham-NAS rats underwent laparotomy and were treated with intraperitoneal (IP) NAS (20 mg/kg); (3) IR rats underwent occlusion of both superior mesenteric artery and portal vein for 30 minutes, followed by 48 hours of reperfusion, and (4) IR-NAS rats underwent IR and were treated with IP NAS (20 mg/kg) immediately before abdominal closure. Intestinal structural changes, Park injury score, enterocyte proliferation, and enterocyte apoptosis were determined 24 hours following IR. The expression of Bax, Bcl-2, p-ERK, and caspase-3 in the intestinal mucosa was determined using real-time polymerase chain reaction, Western blot, and immunohistochemistry. A nonparametric Kruskal-Wallis analysis of variance test was used for statistical analysis with p less than 0.05 considered statistically significant.
Treatment with NAS resulted in a significant increase in mucosal weight in jejunum and ileum, villus height in the ileum, and crypt depth in jejunum and ileum compared with IR animals. IR-NAS rats also had a significantly proliferation rates as well as a lower apoptotic index in jejunum and ileum which was accompanied by higher Bcl-2 levels compared with IR animals.
Treatment with NAS prevents gut mucosal damage and inhibits programmed cell death following intestinal IR in a rat.
N-乙酰血清素（NAS）是褪黑素生物合成过程中一种天然存在的化学中间体。在各种实验模型中的广泛研究表明，NAS治疗可显著保护心脏和肾脏免受缺血再灌注（IR）损伤。本研究的目的是探讨NAS对大鼠肠道缺血再灌注损伤后肠道恢复和肠上皮细胞更新的影响。
将雄性Sprague-Dawley大鼠分为四个实验组：（1）假手术组大鼠接受剖腹手术；（2）假手术-NAS组大鼠接受剖腹手术并腹腔注射（IP）NAS（20mg/kg）；（3）IR组大鼠肠系膜上动脉和门静脉均阻断30分钟，随后再灌注48小时；（4）IR-NAS组大鼠接受IR处理，并在腹部缝合前立即腹腔注射NAS（20mg/kg）。在IR后24小时测定肠道结构变化、帕克损伤评分、肠上皮细胞增殖和肠上皮细胞凋亡。采用实时聚合酶链反应、蛋白质免疫印迹法和免疫组织化学法测定肠黏膜中Bax、Bcl-2、p-ERK和caspase-3的表达。采用非参数Kruskal-Wallis方差分析进行统计分析，P<0.05认为差异有统计学意义。
与IR组动物相比，NAS治疗导致空肠和回肠黏膜重量显著增加、回肠绒毛高度增加以及空肠和回肠隐窝深度增加。与IR组动物相比，IR-NAS组大鼠空肠和回肠的增殖率显著提高，凋亡指数降低，同时Bcl-2水平升高。
NAS治疗可预防大鼠肠道IR后的肠黏膜损伤并抑制程序性细胞死亡。
