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首页> 外文期刊>Current therapeutic research, clinical and experimental. >The Effects of Sirolimus on Target Organs During Mesenteric Ischemia and Reperfusion Damage in an Experimental Rat Model
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The Effects of Sirolimus on Target Organs During Mesenteric Ischemia and Reperfusion Damage in an Experimental Rat Model

机译：西罗莫司对实验性大鼠模型肠系膜缺血再灌注损伤中靶器官的影响

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BACKGROUND: Mesenteric ischemia and reperfusion (I/R) syndrome (MIRS) has been considered a clinicopathologic entity associated with a variety of clinically severe conditions with decreased intestinal blood flow and has been known to induce I/R damage in various organs. Sirolimus (SRL), a macrolide antibiotic isolated from a strain of Streptomyces hygroscopicus, is a potent and nonnephrotoxic immunosuppressant.OBJECTIVE: This study was designed to investigate the potential impact of sirolimus on MIRS-induced I/R damage in renal, intestinal, pulmonary, and hepatic tissues in an experimental rat model.METHODS: Twenty-four male Sprague-Dawley rats, aged 6 to 8 weeks and weighing 280 (+-20 g), were studied. Using computer-generated random numbers, rats were assigned to 1 of the following 3 groups: group 1 (I/R group, n = 8), group 2 (I/R + sirolimus group, n = 8), and group 3 (control group, n = 8). Sirolimus, in a 1 mg/mL (60 mL) solution, was administered intraperitoneally in a dose of 1.5 mg/kg/d to the rats assigned to group 2 starting from 3 days before the surgical procedure. In surgery, a laparotomy was performed to clamp the superior mesenteric artery and, thus, induce bowel ischemia in groups 1 and 2. After 60 minutes of ischemia, the microvascular clamp on the superior mesenteric artery was removed for 3 hours of reperfusion. Soon after experimental induction of MIRS, bowel, lung, kidney, and liver specimens from each animal were harvested for both biochemical and histopathologic analysis.RESULTS: There were statistically significant differences between groups 1 and 3 with regard to degrees of intestinal (P < 0.001), hepatic (P = 0.001), renal (P < 0.001), and pulmonary (P = 0.01) I/R damage. The lung specimens from group 2 had less inflammation and perivascular edema formation compared with specimens from group 1, but no statistical significance was observed between the groups (P < 0.33). There were statistically significant differences between groups 1 ...
机译：背景：肠系膜缺血和再灌注（I / R）综合征（MIRS）被认为是与各种临床严重疾病，肠血流量减少相关的临床病理实体，并且已知会在各种器官中引起I / R损伤。西罗莫司（SRL）是从吸水链霉菌菌株中分离出来的一种大环内酯类抗生素，是一种有效且无肾毒性的免疫抑制剂。方法：研究了24只6至8周龄，体重为280（+-20 g）的雄性Sprague-Dawley大鼠。使用计算机生成的随机数，将大鼠分为以下3组中的1组：第1组（I / R组，n = 8），第2组（I / R +西罗莫司组，n = 8）和第3组（对照组，n = 8）。从外科手术开始前三天开始，以1 mg / mL（60 mL）溶液的西罗莫司腹膜内以1.5 mg / kg / d的剂量腹膜内给予第2组的大鼠。在手术中，进行剖腹手术以夹住肠系膜上动脉，从而在第1组和第2组中引起肠缺血。缺血60分钟后，将肠系膜上动脉上的微血管钳移除，进行3小时的再灌注。实验诱导MIRS后不久，收集每只动物的肠，肺，肾和肝标本进行生化和组织病理学分析。结果：第1组和第3组之间在肠道程度方面有统计学差异（P <0.001 ），肝脏（P = 0.001），肾脏（P <0.001）和肺部（P = 0.01）I / R损伤。与第1组相比，第2组的肺标本的炎症和血管周围水肿形成较少，但各组之间没有统计学意义（P <0.33）。第1组之间存在统计学上的显着差异...

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