Hepatoctye growth factor pretreatment reduces apoptosis and mucosal damage after intestinal ischemia-reperfusion
Hepatoctye growth factor pretreatment reduces apoptosis and mucosal damage after intestinal ischemia-reperfusion
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DOI：
10.1053/jpsu.2002.33884
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发表时间：
2002-07-01
影响因子：
2.4
通讯作者：
Schwartz, MZ
中科院分区：
文献类型：
--
作者：
Kuenzler, KA;Pearson, PY;Schwartz, MZ
背景/目的：肠道缺血再灌注（IR）损伤可导致粘膜损伤和细胞死亡。本研究旨在评估肝细胞生长因子（HGF）预处理对中度IR损伤后肠道的保护作用。方法：对照动物（n = 7）接受48小时静脉注射生理盐水，治疗动物（n = 7）接受HGF（150μg/kg/d）。肠系膜动脉闭塞35分钟和再灌注120分钟后，获得血清和空肠粘膜样本。对己糖胺酶 A (HEX A) 和 β-葡萄糖醛酸酶 (GLUC)（肠细胞坏死的酶标记物）进行荧光测定。通过TUNEL方法对细胞凋亡进行定量。通过多重逆转录聚合酶链反应 (RT-PCR) 评估肿瘤坏死因子-α (TNF-α) 和干扰素-γ (IFN-γ) 的转录，并使用 Student's t 检验进行统计分析。 结果：HGF 预处理后，HEX A 和 GLUC 活性从 543 +/- 28 降低至 343 +/- 35 nmole/h/mL (P < .01)，并且分别为 183 +/- 29 至 119 +/- 22 nmole/h/mL (P < .01)。 IR 损伤后，与未治疗的大鼠 (225 +/- 24) 相比，经过预处理的动物每 10 个隐窝的凋亡细胞数量减少 (33 +/- 11) (P < .01)。与对照组相比，经 HGF 预处理的动物的平均 IFN-gamma 带强度较低 (0.05 +/- 0.02) (0.31 +/- 0.09；P < .05)。结论：HGF 预处理可减少肠道 IR 损伤后严重的隐窝凋亡和细胞坏死。这些数据表明 HGF 可能有益于减轻 IR 损伤，因此可能具有重要的临床应用。版权所有2002，Elsevier Science（美国）。版权所有。
Background/Purpose: Ischemia-reperfusion (IR) injury to the intestine can result in mucosal damage and cellular death. This study was designed to evaluate the protective effects of pretreatment with hepatocyte growth factor (HGF) on intestine after moderate IR injury.Methods: Control animals (n = 7) received 48 hours of intravenous saline, and treatment animals (n = 7) received HGF (150 mug/kg/d). After 35 minutes of mesenteric artery occlusion and 120 minutes of reperfusion, serum and jejunal mucosa samples were obtained. Fluorometric assays were performed for hexosaminidase A (HEX A) and beta-glucuronidase (GLUC), enzyme markers of enterocyte necrosis. Apoptosis was quantified by the TUNEL method. Transcription of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) was assessed by multiplex reverse transcription polymerase chain reaction (RT-PCR) Statistical analysis was performed using the Student's t test.Results: After HGF pretreatment, HEX A and GLUC activities were reduced from 543 +/- 28 to 343 +/- 35 nmole/h/mL (P < .01) and 183 +/- 29 to 119 +/- 22 nmole/h/mL (P < .01), respectively. Pretreated animals had a reduced number of apoptotic cells per 10 crypts (33 +/- 11) compared with untreated rats (225 +/- 24) after IR injury (P < .01). Mean IFN-gamma band intensity was lower in HGF-pretreated animals (0.05 +/- 0.02) compared with controls (0.31 +/- 0.09; P < .05).Conclusions: Pretreatment with HGF reduces the severe crypt apoptosis and cellular necrosis after IR injury to the intestine. These data suggest that HGF may be beneficial in attenuating IR damage and thus may have significant clinical application. Copyright 2002, Elsevier Science (USA). All rights reserved.