摘要
目的:观察纳洛酮对脑缺血再灌注损伤后海马区c-jun氨基末端激酶3(JNK3)表达的影响,探讨纳洛酮的脑保护作用机制。方法:采用线栓法制造大鼠局灶性脑缺血再灌注模型,将SD大鼠随机分为假手术组、缺血再灌注对照组、小剂量纳洛酮给药组、高剂量纳洛酮给药组、SP600125(JNK3抑制剂)给药组及其溶剂组;采用氯化三苯基四氮唑(TTC)染色法检测大鼠缺血再灌注后脑梗死范围;采用免疫印迹法检测海马区JNK3的磷酸化水平。结果:高剂量纳洛酮干预组、SP600125干预组与缺血再灌注组相比脑梗死范围缩小,蛋白JNK3磷酸化水平显著降低;随着干预剂量增加,纳洛酮抑制蛋白JNK3磷酸化水平作用增强。结论:纳洛酮通过抑制脑缺血再灌注损伤后JNK3的磷酸化激活参与了对脑组织的部分保护性作用,其作用呈剂量依赖性。
AIM： To investigate the effect of naloxone on the expression of JNK3 protein in Hippocampus during transient focal cerebral is- chemia reperfusion, and to discuss the probable mechanism of its protective effect. METHODS： The model of focal cerebral ischemia-reperfusion injury was established in rats by suture-occluded method. Rats were randomly divided into several groups, including Sham-operation, ischemia- reperfusion, low dose naloxone treated isehemia- reperfusion, high dose naloxone treated schemia- reperfusion, SP600125 treated ischemia-reperfu- sion and respective Vehicle treated ischemia- reperfusion. The infarction volume was detected by TTC staining. Western Blot was operated to detect expression of p-JNK3 in Hippocampus. RESULTS： Both groups of high dose naloxonetreated ischemia-reperfusion and SP600125 trea- ted ischemia-reperfusion, not only ischemia- reperfusion infarction volume was reduced, but also expression of p-JNK3 was down-regulated, compared with ischemia-reperfusion only group. As the dose increase, the effect of naloxone on inhibiting expression of p-JNK3 was obviously improved. CONCLUSION. Naloxone inhibits the expression of p-JNK3 in a dose-dependent man- ner during focal ischemia reperfusion which may be one of the mechanisms of its neuroprotective function.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2013年第3期258-262,共5页
Chinese Journal of Clinical Pharmacology and Therapeutics
