帕罗西汀对应激抑郁模型大鼠脑区蛋白激酶PKA、PKC和CaMKII活力的影响  

Effects of paroxetine on protein kinase PKA, PKC and CaMKII activity in different brain regions in a rat depression model

作　　者：郑晖[1] 马光瑜[2] 付晓春[1] 杜红光[1] 

机构地区：[1]广东食品药品职业学院,广东广州510520 [2]广东省食品药品监督管理局,广东广州510080

出　　处：《南方医科大学学报》2008年第7期1223-1225,共3页Journal of Southern Medical University

基　　金：广东省自然科学基金(06300495);广东省医学科学技术研究基金(B2005101)~~

摘　　要：目的探讨帕罗西汀对应激抑郁模型大鼠脑区蛋白激酶PKA、PKC和CaMKII活力的影响。方法将成年雄性SD大鼠随机分为6组:对照组(I)、抑郁模型组(II)、抑郁模型+给药1次组(III)、抑郁模型+给药1周组(IV)、抑郁模型+给药2周组(V)和抑郁模型+给药4周组(VI)。抑郁模型为强迫大鼠游泳4周。采用同位素法检测蛋白激酶PKA、PKC和CaMKII的活力。结果(1)在海马,II、III、IV及V组大鼠PKA[分别为(3.92±0.23)×10-2,(3.68±0.092)×10-2,(3.56±0.11)×10-2,和(3.52±0.18)×10-2]和CaMKII[分别为(12.89±0.31)×10-2,(15.08±2.07)×10-2,(16.32±2.87)×10-2,和(17.00±1.52)×10-2]活力明显低于I组[PKA(5.63±0.41)×10-2;CaMKII(48.91±1.86)×10-2]和VI组[PKA(4.92±0.36)×10-2;CaMKII(46.74±1.34)×10-2](P<0.01或P<0.05);II组大鼠PKC的活力[(0.55±0.017)×10-2]明显低于对照组[(1.48±0.27)×10-2](P<0.01),各用药组大鼠海马PKC活力与对照组比较差异无统计学意义(P>0.05)(2)在前额叶皮质,II、III、IV组大鼠PKA活力[分别为(0.9±0.027)×10-2,(0.92±0.081)×10-2,(0.92±0.028)×10-2]与对照组[(0.99±0.072)×10-2]比较差异无统计学意义(P>0.05);而V[(1.14±0.045)×10-2]和VI[(1.27±0.040)×10-2]组的PKA活性则显著高于其它四组(P<0.01);II和III组的PKC活性[分别为(0.15±0.013)×10-2,(0.14±0.007)×10-2)]均显著高于对照组[(0.099±0.0007)×10-2]和其它用药组(P<0.01),IV组PKC活性[(0.11±0.0006)×10-2]与I组比较差异无统计学意义(P>0.05),V和VI组PKC活性[分别为(0.077±0.0005)×10-2,(0.03±0.00017)×10-2]显著低于I组(P<0.01);模型组[(6.84±0.22)×10-2]和各用药组[分别为(6.68±0.23)×10-2,(6.89±0.15)×10-2,(6.55±0.14)×10-2,(6.53±0.13)×10-2]的CaMKII活性显著低于对照组[(16.57±0.19)×10-2](P<0.01)。结论帕罗西汀长期用药逆转慢性应激所致大鼠海马PKA、PKC和CaMKII活力降低,而对前额叶皮质PKA、PKC和CaMKII活力改变的作用复杂。Objective To evaluate the effects of paroxetine on protein kinase PKA, PKC and CaMKII activities in different brain regions in a rat model of depression. Methods Thirty-six adult male SD rats were randomized into 6 groups, including one control group （Ⅰ） and 5 groups of depression model established by forcing the rats to swim for 4 weeks. The 5 depression groups received no treatment （Ⅱ） or were treated with paroxetine at a single dose （Ⅲ）, for a Week （Ⅳ）, 2 weeks （Ⅴ） or 4 weeks （Ⅵ）. The radioactivity of PKA, PKC and CaMKⅡ in the hippocampus and prefrontal cortex was quant-tatively measured using a liquid scintillation counter. Results In the rat hippocampus, PKA and CaMKII activities were significantly lower in groups Ⅱ, Ⅲ, Ⅳ, and V than in groups Ⅰ and Ⅵ （P〈0.01 or P〈0.05）, but comparable between groups Ⅵ and Ⅰ （P〉0.05）. PKC activity was significantly lower in group Ⅱ than in group I （P〈0.01）, but showed no significant difference between the paroxetine-treated groups and group Ⅰ （P〉0.05）. In the prefrontal cortex, the activity of PKA in groups Ⅰ, Ⅱ, Ⅲ, and Ⅳ was similar （P〉0.05）, but all significantly lower than that in groups Ⅴand Ⅵ （P〈0.01）. PKC activity was significantly higher in groups Ⅱ and Ⅲ than that in group Ⅰ and other paroxetine-treated groups （P〈0.01）, and similar between groups Ⅳ and Ⅰ （P〉0.05）; groups Ⅴ and Ⅵ had significantly lower PKC activity than group I （P〈0.01）. Group I had the highest CaMKⅡ activity among the groups （P〈0.01）. Conclusion Chronic administration of paroxetine can reverse chronic stress-induced inhibition of PKA, PKC and CaMKⅡ activity in rat hippocampus, while the effects of paroxetine on the protein kinases can be more complex in prefrontal cortex.

关 键 词：帕罗西汀 抑郁 脑区 PKA PKC CaMKⅡ 

分 类 号：R749.4[医药卫生—神经病学与精神病学]