Puglisi R N, Strande L, Santos M, Doolin E J, Hewitt C W, Whalen T V
Division of Pediatric Surgery, Cooper Hospital, Camden, NJ, USA.
J Pediatr Surg. 1996 Feb;31(2):319-22. doi: 10.1016/s0022-3468(96)90026-3.
Gut ischemia has been implicated in the pathogenesis of necrotizing enterocolitis. Cyclosporine A (CSA), a potent immunosuppressant, attenuates immune/inflammatory cellular reactions. CSA also might be useful for inhibiting cellular immune responses involved in tissue ischemia/reperfusion injury. The authors hypothesized that CSA would attenuate inflammatory cellular changes associated with gut ischemic injury and that these effects could be quantified by computerized morphometry.
Twenty Sprague-Dawley rats underwent 60 minutes of gut ischemia by vascular occlusion of the superior mesenteric vessels. After 1 hour of reperfusion, the ischemic small bowel was harvested for histopathological examination and computerized morphometry, as well as xanthine oxidase (XO, U/mg protein) and maltase (MALT, mmol/L substrate degraded/min/mg protein) assays. CSA (5 mg/kg/d subcutaneously) was given to experimental animals (CSA, n = 10) for 5 days before ischemia, and vehicle was given to controls (CON, n = 10). The computer morphometric parameters studied were: surface index (SI, mucosal surface length per linear unit of intestine), average villous thickness (AVT), and average villous height (AVH).
Results are provided in Table 1.
The results of this study show that CSA may play a role in attenuating ischemia/reperfusion injury in the gut. Enzymatic analysis showed a beneficial role in the preservation of mucosal cell function after gut ischemia/reperfusion injury, as demonstrated by an elevated maltose level. Computerized morphometry demonstrated significant differences in all parameters in the experimental group, showing that CSA does confer gut mucosal protection during ischemia.
肠道缺血与坏死性小肠结肠炎的发病机制有关。环孢素A（CSA）是一种强效免疫抑制剂，可减轻免疫/炎症细胞反应。CSA也可能有助于抑制参与组织缺血/再灌注损伤的细胞免疫反应。作者推测CSA可减轻与肠道缺血性损伤相关的炎症细胞变化，并且这些作用可以通过计算机形态计量学进行量化。
20只Sprague-Dawley大鼠通过肠系膜上血管闭塞进行60分钟的肠道缺血。再灌注1小时后，采集缺血小肠进行组织病理学检查、计算机形态计量学分析，以及黄嘌呤氧化酶（XO，U/mg蛋白）和麦芽糖酶（MALT，mmol/L底物降解量/分钟/mg蛋白）检测。在缺血前5天，给实验动物（CSA组，n = 10）皮下注射CSA（5 mg/kg/d），给对照组（CON组，n = 10）注射赋形剂。所研究的计算机形态计量学参数包括：表面指数（SI，每单位长度肠道的黏膜表面长度）、平均绒毛厚度（AVT）和平均绒毛高度（AVH）。
结果见表1。
本研究结果表明，CSA可能在减轻肠道缺血/再灌注损伤中发挥作用。酶分析显示，在肠道缺血/再灌注损伤后，对黏膜细胞功能的保存有有益作用，麦芽糖水平升高证明了这一点。计算机形态计量学显示实验组所有参数均有显著差异，表明CSA在缺血期间确实能提供肠道黏膜保护。
