腹腔连续注射低剂量氯胺酮后大鼠海马LC3和Beclin1的表达

Expression of LC3 and Beclin1 in rat hippocampus after repeated intraperitoneal administration of low dose of ketamine

目的研究腹腔连续注射低剂量氯胺酮后大鼠海马自噬相关蛋白LC3、Beclin1的表达及其意义。方法 SD大鼠30只随机分为用药组和对照组,用药组大鼠以5mg/kg的剂量腹腔注射氯胺酮,每间隔30min 1次,共5次。对照组予以等量生理盐水。用药组大鼠按用药后时间不同分为6小组,分别于末次给药后1,3,6,12,24,48h后取海马组织备用,用免疫荧光技术和Western blot技术检测大鼠海马组织中LC3、Beclin1的表达,应用统计学处理,比较用药组与对照组的蛋白表达差异。结果与对照组比较,用药组大鼠海马组织中LC3Ⅱ/LC3Ⅰ值在1h表达开始增多,6h呈强表达,Beclinl的表达在6h开始增多,12,24,48h都呈强表达(P<0.05)。结论腹腔连续注射低剂量氯胺酮能促进海马组织发生自噬,自噬增强是对氯胺酮毒性的反应。

Objective To investigate expression of autophagic protein LC3 and Beclinl in the rat hippoeampus after repeated intraperitoneal injection of low dose of ketamine （Ket）. Methods 30 SD rats were randomly divided into ket group and control group. Ketamine was administered intraperitoneally at 5mg/kg every 30 min for 5 times in Ket group. Equal volume of 0. 9% saline was given intraperitoneally to the control rats. Rat hippocampuses were collected at 1,3, 6, 12, 24 and 48h after last administration. LC3 and Beclinl were examined by immunofluorescent staining and Western blot. The ratio of LC3 Ⅱ/LC3 Ⅰ was evaluated. Expression difference was analyzed between ketamine group and control group by statistical analysis. Results The ratio of LC311/LC3Istarted to increase lh after Ket administration and peaked at 6h. The level of Beclinl was elevated at 6h after Ket administration, which was strongly expressed up to 48h. Conclusion It is suggested that upgraded autophagy may occur in rat hippoeampus after repeated administration of low dose of ketarnine, presenting a toxic reaction to ketamine.