N-乙酰-L-半胱氨酸减轻大鼠胃缺血/再灌注损伤的机制  

The protective mechanism of N-acetylcysteine against ischemia/reperfusion induced gastric injury in rats

作　　者：周晓燕[1,2] 杜东书[1] 马小波[1] 张建福[1] 

机构地区：[1]徐州医学院生理学教研室,徐州221002 [2]徐州医学院形态学实验室,徐州221002

出　　处：《生理学报》2010年第1期69-72,共4页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China(No.30570671)

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(150mg/kg),夹闭大鼠腹腔动脉30min,再灌注1h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 subtype1,VR1)拮抗剂(capsaizepin,CPZ)400mg/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。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 30 min 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 cellular apoptosis.Furthermore,NAC increased the protein expression of p-ERK,while inhibited protein expression of p-JNK,NF-κB in gastric 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 rats against 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.

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：R363[医药卫生—病理学]