Slijper Nadav, Sukhotnik Igor, Chemodanov Elena, Bashenko Yulia, Shaoul Ron, Coran Arnold G, Mogilner Jorge
Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Pediatr Surg Int. 2010 Jan;26(1):105-10. doi: 10.1007/s00383-009-2508-6.
Pleiotropic (lipid lowering-independent) effects of statins are attributed to their antiinflammatory, antioxidant, and/or vascular actions. Extensive studies in various experimental models have established that pretreatment with simvastatin significantly protects heart and kidney injured by ischemia-reperfusion (IR). The purpose of the present study was to examine the effect of simvastatin on intestinal recovery and enterocyte turnover after intestinal IR injury in rats.
Male Sprague-Dawley rats were divided into three experimental groups: (1) sham rats underwent laparotomy, (2) IR-rats underwent occlusion of both superior mesenteric artery and portal vein for 30 min followed by 48 h of reperfusion, and (3) IR-SIM rats underwent IR and were treated with oral simvastatin (10 mg/kg) given by gavage immediately before and 24 h after operation. Intestinal structural changes, Park's injury score, enterocyte proliferation and enterocyte apoptosis were determined 24 h following IR. A non-parametric Kruskal-Wallis ANOVA test was used for statistical analysis with P less than 0.05 considered statistically significant.
Treatment with simvastatin resulted in a significant increase in bowel and mucosal weight in ileum, villus height and crypt depth in jejunum and ileum compared to IR animals. IR-SIM rats had also a significantly lower intestinal injury score as well as lower apoptotic index in jejunum and ileum compared to IR animals.
Treatment with simvastatin prevents gut mucosal damage and inhibits programmed cell death following intestinal IR in a rat.
他汀类药物的多效性（不依赖降脂作用）归因于其抗炎、抗氧化和/或血管作用。在各种实验模型中的广泛研究已证实，辛伐他汀预处理可显著保护受缺血再灌注（IR）损伤的心脏和肾脏。本研究的目的是探讨辛伐他汀对大鼠肠道IR损伤后肠道恢复和肠上皮细胞更新的影响。
雄性Sprague-Dawley大鼠分为三个实验组：（1）假手术组大鼠接受剖腹手术；（2）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；（3）IR-SIM组大鼠接受IR处理，并在手术前和术后24小时经口灌胃给予辛伐他汀（10mg/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。采用非参数Kruskal-Wallis方差分析进行统计分析，P<0.05认为具有统计学意义。
与IR组动物相比，辛伐他汀治疗导致回肠肠管和黏膜重量显著增加，空肠和回肠绒毛高度和隐窝深度增加。与IR组动物相比，IR-SIM组大鼠的肠道损伤评分也显著降低，空肠和回肠的凋亡指数也较低。
辛伐他汀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。
