摘要
目的观察l-四氢巴马汀(l-THP)对氯胺酮依赖大鼠条件位置偏爱(CPP)、海马CA1区神经胶质纤维酸性蛋白(GFAP)以及伏隔核ERK磷酸化蛋白表达的影响。方法随机将40只大鼠分为空白对照组、氯胺酮模型组(10 mg/kg)、l-THP低剂量(10 mg/kg)干预组、l-THP高剂量干预(20 mg/kg)组,每天大鼠给药及训练,建立条件位置偏爱模型。采用免疫组化法检测海马CA1区GFAP蛋白,Western blot法检测大鼠伏隔核ERK磷酸化蛋白。结果与空白对照组比较,氯胺酮模型组大鼠在伴药箱时间明显增加(P<0.05),成功建立氯胺酮依赖大鼠条件位置偏爱模型。与模型组比较,l-THP高剂量干预组可明显减少大鼠在伴药箱中的时间(P<0.05)。免疫组化结果显示,与空白对照组比较,氯胺酮模型组GFAP阳性细胞数量明显增多(P<0.05);与模型组比较,l-THP低剂量、高剂量干预组GFAP阳性细胞数量明显减少(P<0.05)。Western blot结果显示,与空白对照组比较,模型组ERK磷酸化蛋白表达明显增加(P<0.05);与模型组比较,l-THP低剂量、高剂量干预组ERK磷酸化蛋白明显降低(P<0.05)。结论 l-THP拮抗氯胺酮依赖与伏隔核p-ERK蛋白表达有关,并且l-THP对氯胺酮依赖大鼠神经元损伤具有保护作用。l-THP对氯胺酮成瘾具有调制作用。
Objective To investigate the effect of 1-tetrahydroplmatine （l-THP） on ERK phosphorylation in nucleus accumbens and GFAP in hippocampus of ketamine-induced conditioned place preference （CPP） rats. Methods Rats were randomly divided into control group, ketamine model group, ketamine with/-THP （10 mg/kg） goup, and ketamine with I-THP （20 mg/kg） group. The rats were adeministered witthdrug and were trained every day to establish the model of conditioned place preference. The immunohistochemistry technique was used to detect the expression of GFAP protein and the western blot was used to detect the expression of ERK phosphorylation in nucleus accumbens. Results Compared with the control group, tthe time that the rats in ketamine model group remaining in non-preferred compartment increased significantly （P 〈 0. 05 ）, indicating in that ketamine place preference model was established successfully. Compared with ketamine model group, the time that the rats in I-THP （20） group spent on white compartment reduced significantly （ P 〈 0. 05 ）. Immunohistochemistry resuts showed that the number of GFAP positive cells in hippocampus CA1 increased in the ketamine model group （ P 〈 0. 05 ）, while in the low and high dosage l-THP group, the number of GFAP positive cells deceased （P 〈 0. 05 ）. Western blot showed that the expression of ERK phosphorylation was significantly increased in the ketamine model group （ P 〈 0. 05 ）, while in the low and high dosage l-THP group were significantly decreased （ P 〈 0. 05 ）. Conclusion The inhibition of ERK phosphorylation may be involved in the effects of l-THP on the modulation of ketamine dependent. l-THP has a protective effect on the neuron damage of ketamine dependent rats. l-THP has a modulate effect on ketamine dependent.
作者
杜艳
王浩江
苏红亮
曹洁
王玉瑾
Du Yan;Wang Haojiang;Su Hongliang;Cao Jie;Wang Yujin(School of Pharmacy,Shanxi Medical University,Taiyuan,030001,China;School of Basic Medical Science,Shanxi Medical University,Taiyuan,030001,China;School of Forensic Medicine,Shanxi Medical University,Taiyuan,030001,China)
出处
《中国法医学杂志》
CSCD
2018年第3期258-262,共5页
Chinese Journal of Forensic Medicine
基金
国家自然科学基金资助项目(81601655)
山西省高等学校科技创新基金资助项目(2017145)
山西省研究生教育创新基金资助项目(2017BY074)
