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N-乙酰-L-半胱氨酸减轻大鼠胃缺血/ 再灌注损伤的机制

周晓燕, 杜东书, 马小波, 张建福

徐州医学院 生理学教研室； 形态学实验室，徐州 221002

摘要

为研究N- 乙酰-L- 半胱氨酸(N-acetylcysteine, NAC)减轻大鼠胃缺血/ 再灌注(gastric ischemia/reperfusion, GI/R)损伤的机制，在大鼠股静脉注射NAC (150 mg/kg)，夹闭大鼠腹腔动脉30 min，再灌注1 h 制备GI/R 模型。取胃后计数胃黏膜损伤指数(gastric mucosal damage index, GMDI)，用原位检测 (TUNEL)法观察胃黏膜细胞的凋亡，用免疫印迹法测定胃黏膜组织中p-ERK，p-JNK 和NF-κB 的表达，用RT-PCR 法检测TNF-α, Caspase-3 的mRNA 表达。结果显示，NAC 可以减轻GI/R 损伤大鼠胃黏膜细胞的凋亡；促进大鼠I/R 损伤的胃黏膜组织中p-ERK 蛋白的表达，抑制p-JNK 和NF-κB 的蛋白表达，同时也抑制TNF-α mRNA 和Caspase-3 mRNA 的表达。股静脉给予辣椒素受体(vanilloid receptor subtype 1,VR1)拮抗剂(capsaizepin, CPZ) 400 mg/kg，能逆转NAC 对大鼠GI/R 损伤的保护作用。以上结果提示：NAC 对大鼠GI/R 损伤具有减轻作用，其保护机制可能是通过上调胃黏膜组织中p-ERK，下调p-JNK 和NF-κB 实现的，且这种保护作用可能与VR1有关。

关键词： N - 乙酰- L - 半胱氨酸; 胃缺血/ 再灌注; 凋亡; 辣椒素受体; 大鼠

分类号：Q426；Q482；R322.81

[The protective mechanism of N-acetylcysteine against ischemia/reperfusioninduced gastric injury in rats.] [Ariticle in Chinese]

ZHOU Xiao-Yan, DU Dong-Shu, MA Xiao-Bo, ZHANG Jian-Fu

Department of Physiology； Laboratory of Morphological Experiments, Xuzhou Medical College, Xuzhou 221002, China

Abstract

The present study aimed to investigate the protective mechanism of N-acetylcysteine (NAC) against gastric ischemia /reperfusion (GI/R) injury in rats. After intravenous injection (IV) of NAC (150 mg/kg) into femoral vein, the rats were subjected to 30min of ischemia induced by clamping the celiac artery followed by 60 min of reperfusion. After the gastric mucosal damage index(GMDI) had been calculated, gastric mucosal cell in situ apoptosis was detected by TUNEL method. The protein expression of p-ERK,p-JNK and NF-κB, and mRNA expression of TNF-α and Caspase-3 in gastric mucosa were evaluated by using Western-blot or RTPCR,respectively. The results showed that NAC not only attenuated the GI-R injury, but also decreased gastric mucosal cellularapoptosis. Furthermore, NAC increased the protein expression of p-ERK, while inhibited protein expression of p-JNK, NF-κB ingastric mucosa. NAC also decreased the expression of TNF-α mRNA and Caspase-3 mRNA in gastric mucosa. Capsazepine (CPZ)(400 mg/kg, IV) reversed the protective effect of NAC against GI/R injury in rats. These results suggest that NAC can protect ratsagainst GI/R injury. This protective effect is possibly mediated by the up-regulation of p-ERK and down-regulation of p-JNK and NF-κB.In addition, vanilloid receptor subtype 1 may be involved in the protective mechanism of NAC against GI/R injury.

Key words: N-acetylcysteine; gastric ischemia/reperfusion; apoptosis; vanilloid receptor subtype 1; rats

收稿日期：2009-09-30　　录用日期：2009-11-26

通讯作者：张建福　　E-mail: jfzhang@xzmc.edu.cn

引用本文：

周晓燕, 杜东书, 马小波, 张建福. N-乙酰-L-半胱氨酸减轻大鼠胃缺血/ 再灌注损伤的机制 [J]. 生理学报 2010; 62 (1): 69-72.

ZHOU Xiao-Yan, DU Dong-Shu, MA Xiao-Bo, ZHANG Jian-Fu. [The protective mechanism of N-acetylcysteine against ischemia/reperfusioninduced gastric injury in rats.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (1): 69-72 (in Chinese with English abstract).