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莪术油注射液对慢性低氧大鼠学习与记忆的影响

孙臣友, 胡伟, 戚双双, 戴开宇, 胡斯旺, 楼新法

解剖学教研室.浙江,温州 325035；第二附属医院药剂科.浙江,温州 325027

摘要

该文旨在探讨莪术油注射液对慢性低氧大鼠学习与记忆的影响及其可能的机制。将Sprague--Dawley大鼠随机分为5组：对照组、慢性低氧组、5 mg/kg莪术油组、10 mg/kg莪术油组、20 mg/kg莪术油组，每组各14只。慢性低氧处理采用低氧舱内吸入大约10% O_(2)、5% CO_(2)，饲养10 h/d，持续饲养28 d。莪术油处理各组入饲养舱前腹腔注射相应浓度的莪术油注射液。实验结束次日，通过Morris水迷宫测试各组动物学习和记忆成绩的变化；测定各组大鼠血清和海马组织丙二醛(malonaldehyde, MDA)含量和超氧化物歧化酶(superoxide dismutase, SOD)活性以及海马组织Ca~(2+)浓度([Ca~(2+)]_(i)）；通过免疫组织化学和Western blot检测磷酸化Ca~(2+)/钙调蛋白依赖性蛋白激酶II (phosphorated Ca~(2+)/calmodulin--dependent protein kinase II, p--CaMKII)在海马组织和胞膜上的表达。与对照组相比，慢性低氧组发生如下变化：隐蔽平台的逃避潜伏期明显延长({sl P}<0.05)；血清和海马组织MDA含量明显增高，SOD活性显著降低({sl P}<0.05, {sl P}<0.01)；海马组织[Ca~(2+)]_(i)明显增高({sl P}<0.01)；海马p--CaMKII表达量显著降低({sl P}<0.01)。与慢性低氧组比较，莪术油各组发生以下变化：10、20 mg/kg莪术油组隐蔽平台的逃避潜伏期显著缩短({sl P}<0.05)；5、10、20 mg/kg莪术油组血清和海马组织MDA含量均显著降低({sl P}<0.05，{sl P}<0.01)；10、20 mg/kg莪术油组血清SOD活性显著增加({sl P}<0.01)；5、10、20 mg/kg莪术油组海马组织[Ca~(2+)]_(i)明显降低({sl P}<0.01)；10、20 mg/kg莪术油组海马p--CaMKII表达也明显增加({sl P}<0.05, {sl P}<0.01)。以上结果提示，慢性低氧导致大鼠学习与记忆能力下降，其机制可能与降低血清和海马组织MDA含量、增加SOD活性、降低海马组织[Ca~(2+)]_(i)和(或)增加海马组织p--CaMKII表达有关。

关键词： 慢性低氧; 莪术油注射液; 学习和记忆; 海马; 磷酸化Ca~(2+)/钙调蛋白依赖性蛋白激酶II

Effect of Rhizoma curcumae oil on the learning and memory in rats exposed to chronic hypoxia and the possible mechanisms

Sun Chenyou, Hu Wei, Qi Shuangshuang, Dai Kaiyu, Hu Siwang, Lou Xinfa

Department of Anatomy, Wenzhou Medical College.Wenzhou 325035,Zhejiang；China

Abstract

The effect of Rhizoma curcumae oil on the learning and memory in rats exposed to chronic hypoxia and the possible mechanismswere investigated. The rats were divided randomly into 5 groups (14 animals in each group): control, chronic hypoxia, chronic hypoxiawith low (5 mg/kg body weight), middle (10 mg/kg body weight) and high (20 mg/kg body weight) concentrations of Rhizoma curcumaeoil injection. The animals undergoing chronic hypoxia were exposed to hypoxia in a hypoxic chamber containing 10% O_(2) and 5% CO_(2) for 10 h/d, lasting 28 d. Morris water maze (MWM) test was used to obtain the scores of leaning and memory. The superoxide dismutase(SOD) activity and malonaldehyde (MDA) content were determined in the serum and hippocampus as well as [Ca~(2+)]_(i) in the hippocampus.The expression of phosphorylated Ca~(2+)/calmodulin-dependent protein kinase Ⅱ (p-CaMKII) in the hippocampus was evaluated by usingimmunohistochemistry and Western blot. Compared with the control group, the chronic hypoxia group showed the following changes:(1) The escape latency to the hidden platform was remarkably prolonged (P<0.05); (2) The content of MDA and [Ca~(2+)]_(i) were obviouslyhigher, but the activity of SOD and the expression of p-CaMKII were significantly lower (P<0.05, P<0.01). Compared with the chronic hypoxia group, groups with Rhizoma curcumae oil injection had the following changes: (1) The escape latency to the hidden platform was remarkably shorter in 10, 20 mg/kg body weight groups (P<0.05); (2) The content of MDA and [Ca~(2+)]_(i) were markedly decreased in 5, 10, 20 mg/kg body weight groups (P<0.05, P<0.01), but the activity of SOD in the serum and the expression of p-CaMKII were significantly higher in 10, 20 mg/kg body weight groups (P<0.05, P<0.01). The results showed that the capacity of learning and memory was degraded following chronic hypoxia. The decrease in MDA content and [Ca~(2+)]_(i) and (or) the increase in SOD activity and p-CaMKII expression might participate in the enhancing effect on learning and memory induced by Rhizoma curcumae oil.

Key words: chronic hypoxia;Rhizoma curcumae oil injection;learning and memory;Hippocampus;phosphorylated Ca~(2+)/calmodulin-dependent protein kinase Ⅱ

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引用本文：

孙臣友, 胡伟, 戚双双, 戴开宇, 胡斯旺, 楼新法. 莪术油注射液对慢性低氧大鼠学习与记忆的影响[J]. 生理学报 2008; 60 (2): 228-234.

Sun Chenyou, Hu Wei, Qi Shuangshuang, Dai Kaiyu, Hu Siwang, Lou Xinfa. Effect of Rhizoma curcumae oil on the learning and memory in rats exposed to chronic hypoxia and the possible mechanisms. Acta Physiol Sin 2008; 60 (2): 228-234 (in Chinese with English abstract).