噻萘普汀与碳酸锂对慢性应激抑郁模型大鼠海马pCREB表达的影响

Objective To research the effects of tianeptine and lithium on expression of pCREB in hippocampus of chronic stress depression rats. Methods All the experimental rats were divided by random into : Group of depression,Group of tianeptine,Group of lithium and Group of control. The rats of Group of depression, Group of tianeptine and Group of lithium were applied stress for 21 days,and meanwhile Group of control had no stress. The rats of Group of tianeptine were fed with tianeptine (50 mg/kg) , Group of lithium were fed with lithium (60 mg/kg) , while another groups were fed with normal sodium of the same volume. The ethology examination was performed by using method of open-field and experiment of fluid consumption. The expression of pCREB was detected by Western-blotting method. Results After the chronic stress,the horizontal crossing numbers,the erection times,the modification times and the percentage of sacchar-consumption of the rats of Group of depression were 23.2±23.0;8. 1 ±7.2; 3.6 ±3.5 and (55.4 ±11.7)% respectively, which were less than Group of control (46.0±18.9;20.3±11.3;8.4±2.7 and (68.5 ±8.2)% ; P＜0.01). The horizontal crossing numbers(28. 1 ±23.0) ,the erection times(12. 1 ± 9.4) and the modification times(5.5 ±3.2) of Group of tianeptine are less than those of Group of control (P ＜ 0. 05), but no significant difference compared with Group of depression; the percentage of sacchar-consumption(62.7 ± 10.6) % ,Group of tianeptine was more than Group of depression (P＜ 0.05 ) , but no obvious difference with Group of control. The horizontal crossing numbers, the erection times, the modification times and the percentage of sacchar-consumption of Group of lithium were less than those of Group of control (P ＜ 0.05), more than those of Group of depression but no significant difference (P ＞ 0.05). In Westernblotting method,the level of pCREB in the hippocampus of Group of depression was less than that of Group of control (P＜ 0.01); that of Group of tianeptine was more than that of Group of depression (P ＜ 0.01) but no obvious difference with Group of control; that of Group of lithium was less than that of Group of control (P＜0. 01) and more than Group of depression (P＜0.01). Conclusion Tianeptine could reverse the reduction of expression of pCREB in hippocampus of chronic stress depression rats and lithium partly did it.     

噻萘普汀对慢性应激大鼠海马体积影响的在体研究

目的 在体观察噻萘普汀对强迫游泳大鼠海马体积的影响.方法 将24只大鼠随机分成4组:对照组(n=6)、4周应激组(n=6)、4周应激生理盐水组(n=6)和4周应激噻萘普汀组(n=6),各应激组大鼠接受连续4周的强迫游泳应激.根据行为学和血清皮质酮水平评定应激效果,4周后行MRI扫描在体检测左右海马的体积.结果 4周应激组、4周应激加水组及4周应激给药组的血清皮质酮水平[(728.67±77.67)ng/ml,(765.37±250.87)ng/ml,(863.49±282.31)ng/ml],均比对照组[(191.60±116.41)ng/ml]明显升高(P＜0.01).左、右侧绝对海马体积比较,4周应激组[(59.45±5.05)mm3,(61.66±5.32)mm3]和4周应激加水组[(61.01±6.06)ng/ml,(61.43±3.12)ng/ml]均比对照组明显减小(P＜0.01);4周应激给药组大鼠均较4周应激组和4周应激加水组明显增加(P＜0.01),而与对照组之间差异无显著性(P＞0.05).大鼠双侧海马相对体积组间比较结果与绝对体积一致.应激后大鼠爬格数与海马体积呈正相关(r=0.557～0.598,P＜0.05).结论 噻萘普汀可逆转强迫游泳慢性应激导致的大鼠双侧海马体积减少.     

萱草花对抑郁模型大鼠行为学及学习记忆的影响

目的 观察萱草花提取物对抑郁模型大鼠行为学及学习记忆能力的影响,评价萱草花的抗抑郁作用及其对学习记忆的干预作用.方法 将大鼠按抽签法随机分为对照组、模型组(应激)、阳性组(应激+盐酸氟西汀),高、中、低剂量组(应激+不同剂量萱草花提取物),每组均12只;应用孤养结合慢性不可预见性应激(CUMS)复制抑郁症模型;采用体质量测定、敞箱实验、糖水消耗实验对照研究各组大鼠行为学的改变;应用Morris水迷宫对照研究大鼠的学习记忆能力.结果 与正常组比较,造模组大鼠体质量、敞箱实验的垂直运动、水平运动均减少(P＜0.01或P＜0.05),糖水消耗量及糖水偏好度降低(P＜0.01),各造模组之间比较无统计学差异(P＞0.05);经治疗后高、中、低剂量组,阳性组大鼠的抑郁样行为较模型组均有不同程度的改善(P＜0.01或P＜0.05),但体质量无明显改善(P＞0.05),垂直运动得分分别为[(41.83±17.63)分;(8.14±4.23)分;(12.73±7.21)分;(23.17±18.75)分;(8.38±3.46)分;(13.50±5.44)分];水平运动得分分别为[(69.92±34.04)分;(28.33±20.36)分;(62.25±15.72)分;(69.42±35.17)分;(49.08±32.85)分;(48.08±21.19)分];水迷宫实验中模型组大鼠目标象限时间,平台停留时间,有效区域停留时间,经过平台次数均少于正常组(P＜0.05或P＜0.01),阳性组及高中剂量组目标象限时间,平台停留时间,有效区域停留时间,经过平台次数均多于模型组(或P＜0.01).结论 萱草花可以部分改善抑郁大鼠的抑郁样行为,具有一定抗抑郁作用,同时萱草花能提高抑郁大鼠的空间学习记忆能力,且与给药剂量有一定关系.

Abstract：

Objective To observe the effects of the extract from daylily on the learning and memory in depression model rats, and to explore its possible mechanism. Methods Rats were randomly divided into control group, model group ( CUMS), the positive group (CUMS + fluoxetine) , high, medium and low dose group (stress + daylily extract in different doses), 12 rats in each group. The depression model was established by combining separation and chronic unpredictable stress. Body mass, open-field-test and sugar consumption experiment were used to evaluate the changes of behaviors in rats. And morris water Maze test was used to evaluate the ability of learning and memory. Results There was no statistically distinction between the rats of each group on weight and the behavioral indicator before modeling. Compared with the control group, the vertical movement,horizontal movement of open box test in the model group were reduced (P＜0.05 ) ,and sugar consumption and preference degree decreased (P<0.05 ).The target quadrant time, platform resident time, effective area residence time and crossing platform times in the water maze test of the model group was less than those of the control group. The daylily effect was evaluated at 0, 7, 14, 21, 28, 35, 42 days respectively post treatment. There were significant differences in depression behaviors between model group and daylily group(P＜0.05). And each indicator in the water maze test of the daylily group (high, medium dose) was more than that of model group (P ＜ 0. 05). Control group, model group, positive group, high, medium and low dose group, vertical movement scores were (41.83 ± 17.63; 8.14 ±4.23; 12.73 ±7.21; 23.17 ± 18.75; 8.38 ±3.46; 13.50 ±5.44); horizontal movement scores were (69.92 ±34.04; 28.33 ±20.36; 62.25 ± 15.72; 69.42 ±35.17 ; 49.08 ±32.85; 48.08 ±21.19). Conclusion Daylily may be partially work on the depression of rats, with some antidepressant effect, meantime,daylily can improve the ability of learning and memorizing of the depressed rats.     

慢性脑低灌注大鼠海马神经元损伤的机制研究

目的 探究慢性脑低灌注大鼠海马神经元损伤的机制.方法 双侧颈总动脉结扎(2VO)制备慢性脑低灌注大鼠模型,2VO术后8周取材,分别进行HE染色、电镜、流式细胞术以及Western Blotting检测.结果 HE结果显示2VO组的海马神经元排列稍紊乱,且数量与假手术对照相比有不同程度减少[CA2区:(34.75±3.40)个,(49.25±9.67)个,P＜0.05;DG区:(73.50±9.26)个,(90.75±4.35)个,P＜0.05];电镜观察发现2VO组大鼠海马区部分神经元胞核中略有固缩,出现异染色质边集,胞浆则出现水肿,以线粒体与内质网尤甚;流式细胞术结果表明2VO组海马神经元早期凋亡率[(9.117±2.540)%]高于假手术对照组[(4.750±3.481)%],差异有统计学意义(P＜0.05);Western Blotting检测发现procaspase-3在2VO组大鼠海马的表达与假手术对照组差异无显著性(P＞0.05).结论 慢性脑低灌注大鼠海马神经元的损伤主要由凋亡造成.

Abstract：

Objective To explore the the cellular damage of hippocampus neuron in a rat model of chronic cerebral hypoperfusion. Methods Rat model of chronic cerebral hypoperfusion was established by permanent bilateral common carotid arteries occlusion (2VO). Eight weeks after the operation,the brains were removed and examined with histological stains, electron microscope, flow cytometer and Western Blotting. Results Compared with the control group,the arrangement of hippocampus neurons in 2VO rats appeared to be more irregular, and the number of the neurons decreased partly ( CA2: ( 34.75 ± 3.40) vs (49.25 ± 9.67 ), P ＜ 0. 05; DG: ( 73.50 ± 9.26)vs ( 90.75 ± 4.35 ), P ＜ 0. 05 ). By electron microscopic study of hippocampus neurons in 2VO rats, the nuclei became smaller and the heterochromatin assembled in the border of the nuclei in some neurons, while cytoplasm swelled,especially in mitochondria and endoplasmic reticulum. The rate of apoptosis of hippocampus neurons in 2VO rats( (9. 117 ±2. 540)% ) ,detected by the flow cytometer,was higher than that of sham group( (4. 750 ±3.481 ) % ) (P ＜ 0. 05 ). The expression of pro-caspase-3 in hippocampus of 2 VO rats was not altered significantly compared with the control group(P ＞ 0. 05 ). Conclusion The cellular damage of hippocampus neuron in 2VO rats was mainly caused by apoptosis.     

Relation between plasma atrial natriuretic peptide (ANP) and glomerular ANP receptors in 5/6 nephrectomized rats.

Chronic renal failure (CRF) was induced in male wistar rats (Group I) by 5/6 nephrectomy and the sham-operated ones served as control (Group II). The results showed that in Group I, plasma atrial natriuretic peptide (ANP) levels increased progressively as the Scr was elevated. Plasma R-A rose simultaneously compared to the normal (P less than 0.001). At the 20th week after operation, urine volume and Na decreased significantly (P less than 0.05). The number of glomerular receptors decreased markedly at the 12th week (P less than 0.05) and 20th week (P less than 0.01). Our data suggest that in 5/6 nephrectomized rats, the elevation of plasma ANP level might be partly caused by the damage of glomerular ANP receptors, and the elevated plasma ANP could not play its role in diuresis, natriuresis, blood pressure depression and R-A inhibition as a result of the damage of kidney ANP receptors.

     

氟西汀和噻萘普汀对慢性应激抑郁模型大鼠海马Bcl-2表达的影响

 目的 研究抗抑郁药物氟西汀与噻萘普汀对慢性应激抑郁模型大鼠海马神经元Bcl-2蛋白表达的影响。方法 将大鼠随机分为抑郁模型组、氟西汀组、噻萘普汀组和对照组。模型组、氟西汀组和噻萘普汀组给予21 d的应激刺激,此期间对照组正常饲养,刺激期间氟西汀组每天灌胃氟西汀（10 mg/kg）,噻萘普汀组每天灌胃噻萘普汀（50 mg/kg）,模型组和对照组每天灌胃等体积的生理盐水。行为学检测应用开场法和液体消耗实验。采用Western-blot法检测各组大鼠海马神经元Bcl-2蛋白的表达情况。结果 应激后模型组水平穿越格数、竖立次数、修饰次数、糖水消耗百分比均显著低于对照组（P0.05）。在Western-blot检测中,慢性应激后模型组大鼠海马Bcl-2的表达水平显著低于对照组（P0.05）;噻萘普汀组大鼠海马Bcl-2的表达水平高于模型组（P0.05）。结论 慢性应激可能导致大鼠海马Bcl-2表达降低,氟西汀和噻奈普汀可能逆转慢性应激抑郁模型大鼠海马中Bcl-2表达的降低。     

苯并芘对断乳大鼠学习记忆能力的影响及机制研究

目的 探讨不同剂量苯并(a)芘[B(a)P]对断乳大鼠学习记忆能力的影响及其机制.方法 将40只SD断乳大鼠(28d)随机分为5组,空白对照组、溶剂对照组、3个染毒组(浓度分别为5,10和20mg/kg体质量),隔日腹腔染毒30d.染毒结束后用Morris水迷宫试验观察,免疫组化法测定海马组织中N-甲基-D天门冬氨酸受体NR2B亚基(NMDAR2B)和脑源性生长因子(BDNF)含量.结果 Morris水迷宫试验结果显示,随B(a)P染毒剂量的增加,逃避潜伏期呈递减趋势,高剂量组[(62.78 ±47.25)s]与对照组[(40.60 4-38.79)s]相比,差异有统计学意义(P<0.01);跨台次数随染毒剂量的增加逐渐减少,高剂量组[(4.33 ± 2.08)次]与对照组[(11.25 ± 2.63)次]相比.差异有统计学意义(P＜0.05);随染毒剂量增加,海马区NMDAR2B灰度值呈递减趋势,高剂量组(150.38 ± 15.34)与对照组(162.23±6.56)相比,差异有统计学意义(P＜0.05);BDNF灰度值除低剂量组外呈递减趋势,高剂量组(141.83 ±13.37)与对照组(163.13±8.09)、低剂量组(164.56±9.10)相比均差异有统计学意义(P＜0.05).结论 亚急性B(a)P暴露可降低断乳大鼠空间学习记忆能力,其机制可能与B(a)P影响海马NMDAR2B和BDNF的表达有关.

Abstract：

Objective To investigate the changes and mechanism of learning and memory in rats by different doses of benzo (a) pyrene (B(a)P). Methods Forty weaned rats (28 days) were randomly divided into control group (NS), solvent group ( vegetable oil) and three B (a) P dosage groups (the doses were 5,10 and 20 mg / kg body weight respectively ). And all rats were administrated intraperitoneally every other day to one month. The capability of learning and memory in rats were measured by Morris water maze test, and the brain-derived neurotrophic factor ( BDNF) and NMDAR2B content in hippocampus were tested by immunohistochemistry. Results In training of Morris water maze,the average escape latency was extended gradually with increasing dose, and there was a statistically significant difference between high-dose group((62. 78 ±47. 25 )s) and the control group((40.60±38.79)s)(P＜ 0.01). Compared with the control group(11.25 ±2.63), the number of crossplatform of high-dose group(4.33 ±2.08) was statistically reduced (P＜0.05). B(a)P at 10 and 20 mg/kg decreased NMDAR2B and BDNF expression in hippocampus of rats in immunohistochemistry. The level of NMDAR2B was (162.23 ±6.56) in the high-dose group and (150.38 ± 15.34) in the control group(P＜0.05);the expression level of BDNF was (163. 13 ± 8.09) in the high-dose group and (141.83 ± 13.37) in the control group(P＜ 0.05). Conclusion Subacute B(a)P exposure can reduce spatial learning and memory in weaning rats, it may be related to decreased levels of NMDAR2B and BDNF in hippocampus.     

电磁辐射对大鼠海马NMDA受体NR1亚单位蛋白及其mRNA表达的影响

目的 探讨2000 μW/cm2电磁辐射对大鼠海马N-甲基-D-门冬氨酸(NMDA)受体NR1亚单位蛋白及其mRNA水平表达的影响,揭示电磁辐射对大鼠学习记忆功能的损伤机制.方法 实验分为空白对照组,假辐射组,1 h/d、2h/d、3 h/d辐射组.将辐射组大鼠固定体位,头部接受功率密度为2000μW/cm2的近场辐射,连续辐射30d.通过Morris水迷宫检测大鼠的空间学习记忆能力,采用免疫组化法和Western-Blot法检测大鼠海马组织NR1蛋白表达的变化,RT-PCR法检测大鼠海马组织NR1 mRNA表达的变化.结果 各辐射组大鼠在水迷宫检测第4天寻找安全平台的逃避潜伏期分别为1 h/d[(12.29±1.36)s]、2 h/d[(17.99±2.25)s]、3 h/d[(24.66±5.56)s],均明显长于空白对照组[(8.8±1.66)s](P＜0.05);1 h/d、2 h/d和3 h/d辐射组大鼠海马神经元均排列紊乱,NR1阳性细胞比率明显低于空白对照组,海马组织NR1蛋白[分别为(0.122±0.026)、(0.102±0.023)、(0.060±0.009)]及其mRNA[分别为(0.46±0.07)、(0.35±0.05)、(0.12±0.02)]表达水平较空白对照组[(10.70±0.11)、(0.68±0.11)]均明显降低(P＜0.05).而假辐射组大鼠各项指标与空白对照组相比均无显著差异(P＞0.05).结论 2000μW/cm2电磁辐射可导致大鼠学习记忆功能下降,其机制可能与大鼠海马组织NR1蛋白及其mRNA的表达降低有关.

Abstract：

Objective To evaluate the effects of electromagnetic irradiation of 2000 μW/cm2 exposure on mRNA and protein expression levels of immunoreactive protein and mRNA of NMDAR1 in rats hippocampal,and to explore the impaired mechanism of electromagnetic irradiation on learning and memory.Methods Rats were randomly divided into normal control group, sham-radiated group, and 1 h/d, 2 h/d, and 3 h/d radiation groups.The rats in the radiation groups were fixed and recieved microwave exposure of 2000 μW/cm2, then their learning and memory abilities were tested by Morris water maze experiment, the change of NR1 protein in hippocampal neurons of each group of rats was measured with immunohistochmistry and western blot techniques, and the expression of NR1 mRNA in hippocampus was determined by RT-PCR.Results In the water maze test,compared with the normal control group (8.8 ± 1.66 ), the escape latency of three radiated groups rats ( 1 h/d ( 12.29 ±1.36) s,2 h/d ( 17.99 ±2.25) s,and 3 h/d (24.66 ±5.56) s) were significantly longer (P＜0.05).In the radiation group,the hippocampal neurons of rats showed evident reduction in the ratio of NR1 positive cells,irregular,and arrayed in disorder.Moreover,compared with the normal control group ( (0.70 ±0.11 ), (0.68 ±0.11 ) ) ,the expession of NR1 protein ( 1 h/d (0.122 ±0.026) ,2 h/d (0.102 ±0.023) ,and 3 h/d (0.060 ± 0.009) ) and its mRNA ( 1 h/d (0.46 ±0.07) ,2 h/d (0.35 ±0.05) ,and 3 h/d (0.12 ±0.02) ) in hippocampal neurons was significantly decreased (P＜0.05).Among the indicators, there was no significant difference between sham-radiated group and normal control group.Conclusions Electromagnetic irradiation of 2000 μW/cm2 exposure can impair the learning and memory abilities of rats possibly through a mechanism correlated with the lower expression of NR1 protein and its mRNA in hippocampus.     

萱草花对抑郁模型大鼠行为学及学习记忆的影响

Objective To observe the effects of the extract from daylily on the learning and memory in depression model rats, and to explore its possible mechanism. Methods Rats were randomly divided into control group, model group ( CUMS), the positive group (CUMS + fluoxetine) , high, medium and low dose group (stress + daylily extract in different doses), 12 rats in each group. The depression model was established by combining separation and chronic unpredictable stress. Body mass, open-field-test and sugar consumption experiment were used to evaluate the changes of behaviors in rats. And morris water Maze test was used to evaluate the ability of learning and memory. Results There was no statistically distinction between the rats of each group on weight and the behavioral indicator before modeling. Compared with the control group, the vertical movement,horizontal movement of open box test in the model group were reduced (P＜0.05 ) ,and sugar consumption and preference degree decreased (P<0.05 ).The target quadrant time, platform resident time, effective area residence time and crossing platform times in the water maze test of the model group was less than those of the control group. The daylily effect was evaluated at 0, 7, 14, 21, 28, 35, 42 days respectively post treatment. There were significant differences in depression behaviors between model group and daylily group(P＜0.05). And each indicator in the water maze test of the daylily group (high, medium dose) was more than that of model group (P ＜ 0. 05). Control group, model group, positive group, high, medium and low dose group, vertical movement scores were (41.83 ± 17.63; 8.14 ±4.23; 12.73 ±7.21; 23.17 ± 18.75; 8.38 ±3.46; 13.50 ±5.44); horizontal movement scores were (69.92 ±34.04; 28.33 ±20.36; 62.25 ± 15.72; 69.42 ±35.17 ; 49.08 ±32.85; 48.08 ±21.19). Conclusion Daylily may be partially work on the depression of rats, with some antidepressant effect, meantime,daylily can improve the ability of learning and memorizing of the depressed rats.     

Effects of Tongguan Capsule(通冠胶囊)on Post-myocardial Infarction Ventricular Remodeling and Cardiac Function in Rats

<正>Objective:To observe the effects of Tongguan Capsule(通冠胶囊,TGC) on post-myocardial infarction ventricular remodeling and heart function in rats.Methods:A rat model of acute myocardial infarction (AMI) was established by coronary ligation.Experimental rats were randomized to 4 groups including three model groups(Group A:captopril 5 mg/kg·day,n=7;Group B:TGC 10 g/kg·day,n=7;and Group C:placebo, n=8),and a sham-control group(Group D:blank control,n=6).Animals were treated for 4 weeks.The cardiac function of rats was assessed at the end of the experiment based on left ventricular ejection fraction(LVEF) and left ventricular short axis fractional shortening(LVFS) detected by colored echocardiography;meanwhile, the condition of ventricular remodeling was observed through the levels of left ventricular mass(LVM),plasma aldosterone(ALD),myocardial angiotensinⅡ(AngⅡ) and myocardial collagen measurements.Results:At the end of the experiment,LVEF and LVFS in Group A and B were improved significantly,while those in Group C were unchanged,the LVEF in Group A,B,C,and D was 0.57±0.46,0.61±0.08,0.36±0.55 and 0.76±0.02,respectively;and their LVFS was 0.31±0.52,0.34±0.04,0.23±0.57 and 0.45±0.03,respectively.The difference was statistically significant when comparing the two indexes in Group A and B with those in Group C and D(P0.05).LVM,levels of plasma ALD and myocardial AngⅡwere lower in Group A and B than in Group C,but a comparison between Group A and B showed an insignificant difference in lowering LVM and ALD,while the lowering of AngⅡwas more significant in Group B than in Group A(754.7±18.7 pg/mL vs 952.6±17.6 pg/ mL,P0.05).Morphological examination showed that in Group A and B the swollen myocardial cells had shrunk, with regularly arranged myocardial fibers and decreased collagen proliferation,but the improvements in Group B were more significant.Conclusion:TGC could markedly improve the post-infarction ventricular remodeling and cardiac function in rats,showing that the efficacy was better than or equal to that of captopril.     

抗抑郁药物对慢性应激抑郁模型大鼠海马蛋白激酶C表达的干预作用

目的探讨氟西汀与噻奈普汀对慢性应激模型大鼠海马蛋白激酶C(PKC)表达的影响。方法将60只雄性Wistar大鼠随机分为抑郁模型组、氟西汀组、噻奈普汀组和正常对照组,各15只。模型组、氟西汀组和噻奈普汀组大鼠给予21 d的应激刺激,此期间正常对照组正常饲养,刺激期间氟西汀组每天灌胃氟西汀(10 mg/kg),噻奈普汀组每天灌胃噻奈普汀(50 mg/kg),模型组和正常对照组大鼠每天灌胃等体积的0.9%氯化钠注射液。行为学检测应用开场法和液体消耗实验。采用Western-blotting法检测各组大鼠海马PKC的表达情况。结果应激后,模型组大鼠水平穿越格数、竖立次数、修饰次数、糖水消耗百分比均显著低于正常对照组(P<0.01);氟西汀组水平穿越格数、竖立次数、修饰次数和糖水消耗百分比均显著高于模型组(P<0.05);噻奈普汀组糖水消耗百分比显著高于模型组(P<0.05)。在Western-blotting法检测中,模型组大鼠海马PKC的表达水平显著低于正常对照组(P<0.01);氟西汀组大鼠海马PKC的表达水平显著高于模型组(P<0.01),与正常对照组比较差异无统计学意义(P>0.05);噻奈普汀组大鼠海马PKC的表达水平显著高于模型组(P<0.01),但仍显著低于正常对照组(P<0.01)。结论氟西汀可以逆转慢性应激抑郁模型大鼠海马中PKC表达的降低;噻奈普汀可以部分逆转慢性应激抑郁模型大鼠海马中PKC表达的降低。     

慢性应激抑郁模型大鼠海马cAMP反应元件结合蛋白的表达及氟西汀的干预作用

目的 研究慢性应激抑郁模型大鼠海马cAMP反应元件结合蛋白(CREB)的表达情况及氟西汀的干预作用.方法 将大鼠随机分为抑郁模型组、氟西汀治疗组和对照组.模型组和氟西汀组给予21d的应激刺激,此期间对照组正常饲养,刺激期间氟西汀组每天腹腔注射氟西汀(10mg/kg),模型组和对照组每天腹腔注射等体积的生理盐水.行为学检测应用open-field法和液体消耗实验.采用免疫组织化学法和Western-blotting法检测各组大鼠海马CREB的表达情况.结果 应激后,模型组水平穿越格数[(8.2 ±2.7)格、竖立次数(8.1±3.5)次、修饰次数(4.3±1.6)次]、糖水消耗百分比[(52.5 ±7.8)%]均显著低于对照组[分别为(31.3±5.8)%、(13.9 ±3.2)%、(10.6 ±2.4)%、(68.3 ±4.5)%;均P＜0.01].应激后氟西汀组水平穿越格数[(15.3±7.7)格]低于对照组(P＜0.01),但高于模型组(P＜0.05);竖立次数[(8.2±5.6)次]低于对照组(P＜0.01),与模型组差异无显著性(P＞0.05);修饰次数[(6.2 ±1.5)次]低于对照组(P＜0.01),但高于模型组(P＜0.05);糖水消耗百分比(66.7 ±5.1)%与对照组差异无显著性(P＞0.05),但高于模型组(P＜0.05).免疫组织化学检测和Western-blotting法检测中,模型组大鼠海马CREB的表达均显著低于对照组(P＜0.01);氟西汀组大鼠海马CREB的表达均显著低于对照组(P＜0.01),但高于模型组大鼠(P＜0.01).结论 慢性应激抑郁模型大鼠海马中CREB的表达降低并可以被氟西汀部分逆转.     

碳酸锂对慢性应激抑郁模型大鼠海马蛋白激酶A和蛋白激酶C表达的影响

  目的 研究碳酸锂对慢性应激抑郁模型大鼠海马蛋白激酶A（PKA）和蛋白激酶C（PKC）表达的影响。方法 将大鼠随机分为抑郁模型组、碳酸锂组和对照组。模型组和碳酸锂组给予21 d的应激刺激,此期间对照组正常饲养,刺激期间碳酸锂组每天灌胃给予碳酸锂（60 mg/kg）,模型组和对照组每天灌胃给予等体积的生理盐水。应用open-field法和液体消耗实验进行行为学检测。采用Western blot检测各组大鼠海马PKA和PKC的表达情况。结果 应激后,模型组大鼠水平穿越格数、竖立次数、修饰次数和糖水消耗百分比均显著低于对照组,碳酸锂组水平穿越格数和糖水消耗百分比低于对照组（P0.05）。Western blot结果显示,模型组大鼠海马PKA和PKC的表达水平显著低于对照组（P0.05）。结论 碳酸锂可以逆转慢性应激抑郁模型大鼠海马中PKA和PKC表达的降低,碳酸锂对PKC表达的影响大于对PKA的影响。     

氟西汀和碳酸锂对慢性应激抑郁模型大鼠海马脑源性神经营养因子表达的影响

目的探讨氟西汀与碳酸锂对慢性应激抑郁模型大鼠海马脑源性神经营养因子(BDNF)表达的影响。方法将60只雄性Wistar大鼠随机分为抑郁模型组、氟西汀组、碳酸锂组和对照组,各15只。抑郁模型组、氟西汀组和碳酸锂组大鼠给予21 d的应激刺激,此期间对照组大鼠正常饲养;刺激期间氟西汀组大鼠每天灌胃氟西汀(10mg/kg),碳酸锂组大鼠每天灌胃碳酸锂(60 mg/kg),抑郁模型组和对照组大鼠每天灌胃等体积的0.9%氯化钠注射液。行为学检测应用开场法和液体消耗实验。采用Western blot法检测各组大鼠海马BDNF的表达情况。结果应激后:抑郁模型组大鼠水平穿越格数、竖立次数、修饰次数、糖水消耗百分比均显著低于对照组(P<0.01);碳酸锂组大鼠水平穿越格数、竖立次数、修饰次数、糖水消耗百分比显著低于对照组(P<0.05);氟西汀组大鼠水平穿越格数、竖立次数、修饰次数和糖水消耗百分比均显著高于抑郁模型组(P<0.05),水平穿越格数和竖立次数显著低于对照组(P<0.05),修饰次数和糖水消耗百分比与对照组比较差异无统计学意义(P>0.05)。在Western blot法检测中,抑郁模型组大鼠海马BDNF的表达水平显著低于对照组(P<0.01);碳酸锂组大鼠海马BDNF的表达水平显著高于抑郁模型组(P<0.01),但仍显著低于对照组(P<0.01);氟西汀组大鼠海马BDNF的表达水平显著高于抑郁模型组(P<0.01),与对照组比较差异无统计学意义(P>0.05)。结论慢性应激可以导致大鼠海马BDNF表达降低,氟西汀和碳酸锂可以逆转慢性应激抑郁模型大鼠海马中BDNF表达的降低,且氟西汀的效果优于碳酸锂。     

噻奈普汀与氟西汀对应激大鼠旷场行为及血清皮质酮水平影响的比较研究

目的 比较噻奈普汀与氟西汀对应激导致大鼠行为及血清皮质酮浓度改变的影响及其抗抑郁机制.方法 将33只大鼠随机分为对照组(n ＝6)、应激给水组(n ＝6) 、应激给噻奈普汀组(n ＝6)和应激给氟西汀组(n ＝15),各应激组大鼠连续给予强迫游泳试验4周,每天持续15 min.游泳后给予灌胃,应激给药组分别按50 mg/kg给予噻奈普汀生理盐水溶液、按4 mg/kg给予氟西汀生理盐水溶液灌胃,应激给水组按相同比例给予生理盐水灌胃,采用旷场实验(Open-Field test)法评定行为,使用酶联免疫吸附测定法(ELISA)测定血清皮质酮水平,用单因素方差检验进行组间比较,两两比较采用LSD法.结果 应激给氟西汀组大鼠爬格数[(73.53±43.66)次]和直立次数[(10.00±11.14)次]明显高于应激给水组爬格数[(7.67±3.01)次,P ＜0.01]和直立次数[(0.67±0.82)次,P ＜0.05],而与对照组和应激给噻奈普汀组相比差异无显著性;应激给氟西汀组修饰次数[(3.40±2.47)次,P ＜0.01]和应激给水组[(3.17±3.19)次,P ＜0.05]明显低于对照组[(7.00±1.79)次],而与应激给噻奈普汀组[(4.67±2.34)次]相比差异无显著性.对照组血清皮质酮[(191.60±116.41)ng/ml]和应激给氟西汀组[(315.49±146.35)ng/ml]均明显低于应激给水组[(765.37±250.87)ng/ml,P ＜0.01]和应激给噻奈普汀组[(863.49±282.31)ng/ml,P ＜0.01];对照组血清皮质酮与应激给氟西汀组相比差异无显著性,应激给水组血清皮质酮与应激给噻奈普汀组相比差异无显著性.结论 噻奈普汀与氟西汀均可以有效逆转应激所致行为学改变, 且后者在改善慢性应激所致的抑郁状态更显著;氟西汀对应激大鼠皮质酮激素水平的逆转作用较噻奈普汀显著.     

噻奈普汀对慢性应激大鼠海马N-乙酰天冬氨酸和胆碱复合物代谢水平的影响

目的 探讨慢性应激对大鼠行为和在体海马代谢物浓度的影响以及噻奈普汀的药理作用.方法 将24只大鼠随机分成4组:对照组、4周应激组、4周应激加水组、4周应激用药组.采用强迫游泳试验,建立应激模型.应激后给予灌胃给药,4周应激组给予噻奈普汀50mg/kg,4周应激加水组按相同比例给予生理盐水.根据行为学和血清皮质酮水平评定应激效果,利用1H-MRS测量大鼠双侧海马N-乙酰天冬氨酸/肌酸(NAA/Cr)和胆碱复合物/肌酸(Cho/Cr)比值.结果 4周对照组皮质酮的水平明显低于其他组(P＜0.01),1H-MRS在体检测左侧海马NAA/Cr浓度4周应激用药组(1.287±0.061),对照组(1.304±0.088)明显高于4周应激组(1.035±0.039)和4周应激加水组(1.020±0.085)(P＜0.01),用药组和对照组差异无显著性,应激组和应激加水组差异无显著性.右侧海马NAA/Cr浓度4周应激用药组(1.278±0.080)和对照组(1.268±0.070)明显高于4周应激组(1.015±0.049)和4周应激加水组(1.021±0.067)(P＜0.01),用药组和对照组差异无显著性(P＞0.01),应激组和应激加水组差异无显著性(P＞0.01).双侧Cho/Cr值检测结果各组间均差异无显著性.结论 双侧海马在体NAA/Cr浓度降低提示,强迫游泳应激可以导致大鼠海马神经元生存活力的下降或结构破坏;噻奈普汀作为一种新型抗抑郁药可以对抗这一改变.     

发作间癎样放电致大鼠海马CaMKIV/CREB信号途径紊乱研究

目的 探讨癫癎性情感行为障碍与认知功能受损的神经生物学机制.方法 在海马电点燃及发作间癎样放电(IED)动物模型基础上,将64只Wistar大鼠随机分为IED、海马点燃、电极对照和正常对照4组(每组n ＝16).采用蛋白质免疫印迹法动态观测实验动物海马Ca2+/CaM依赖性蛋白激酶IV(CaMKIV)与核转录因子cAMP反应元件结合蛋白(CREB) 介导的核转录途径的变化规律.结果 电点燃后1 d,IED组与海马点燃组大鼠海马CaMKIV [2组值分别为(2.97±0.88)和(3.06±0.92)]与CREB[(4.23±1.25)和(3.09±0.93)]、磷酸化CREB[pCREB,(3.39±0.97)和(2.92±0.86)]及CREB结合蛋白[CBP,(2.82±0.82)和(3.35±0.98)]表达均较电极对照及正常对照组增高[电极对照组CaMKIV、CREB、pCREB与CBP表达分别为(0.92±0.27)、(1.15±0.34)、(1.07±0.32)与(0.96±0.28);正常对照组分别为(0.89±0.26)、(1.06±0.31)、(1.24±0.35)与(1.04±0.31)],差异具有显著性(P＜0.01).14 d时IED组大鼠再次明显增高[CaMKIV、CREB、pCREB及CBP分别为(2.65±0.78)、(3.96±1.15)、(3.95±1.15)及(4.59±1.34)],与海马点燃组及两对照组相比,差异具有显著性(P＜0.05).结论 IED所致海马CaMKIV/CREB信号途径较长时间的激活,在痫样放电引发的长时程情感行为异常与学习和记忆能力受损中可能有重要意义.     

γ-氨基丁酸联合舍曲林对慢性应激抑郁大鼠认知功能及海马神经元形态的影响

目的 探讨γ-氨基丁酸联合舍曲林对慢性应激抑郁大鼠认知功能及海马神经元形态的影响.方法 采用慢性轻度不可预见性应激建立慢性应激抑郁大鼠模型;模型组、舍曲林组、GABA组及研究组大鼠分别给予腹腔注射生理盐水、舍曲林、GABA、GABA+舍曲林21 d,对照组不予任何刺激和药物;采用敞箱试验和电迷宫试验测定大鼠的行为和记忆能力;Nissl染色观察各组大鼠海马CA1、CA3区锥体细胞神经元形态.结果 应激后,接受应激的4组的水平运动、垂直运动、修饰运动较对照组相比显著减少(P＜0.05或0.01).用药后研究组和舍曲林组的水平运动[分别为(57.25±18.79)格,(39.00±13.69)格]、垂直运动[分别为(23.25±7.01)次,(16.75±4.71)次]、修饰运动[分别为(2.25±0.46)次,(2.25±1.04)次]以及电迷宫的正确反应次数[分别为(17.00±1.93)次,(16.88±2.64)次]、潜伏期时间[分别为(172.88±26.91)s,(206.00±33.54)s]均明显好于模型组(P＜0.05或0.01),GABA组潜伏期时间较模型组显著缩短(P＜0.05).与对照组相比,舍曲林组、GABA组和研究组的CA1、CA3区锥体细胞神经元在形态、密集度、排列方面均有不同程度的改善,其中研究组的改善最明显.结论 GABA联合舍曲林能保护慢性应激抑郁大鼠的海马神经元,从而改善其认知功能.