高压氧对递增负荷训练大鼠腓肠肌P53、Bcl-2蛋白表达的影响

背景：研究显示高压氧疗法在运动损伤与疲劳恢复方面具有较好的应用效果,但其机制尚不清楚。 目的：观察高压氧对递增负荷跑台运动后大鼠腓肠肌P53、Bcl-2蛋白表达及细胞凋亡的影响。 设计、时间及地点：随机对照动物实验,于2008-03/05在苏州大学运动人体科学实验室完成。 材料：2个月龄雄性SD大鼠24只,随机分为3组,安静对照组、递增负荷训练组、高压氧恢复组,每组8只。 方法：递增负荷训练组：坡度10%,递增负荷训练,第1~4周,每天20 m/min运动10 min,25 m/min运动10 min,30 m/min运动10 min,35 m/min运动10 min。第5~8周,每天20 m/min运动10 min,25 m/min运动10 min,30 m/min运动20 min,35 m/min运动20 min。高压氧恢复组：运动方案相同,运动后即刻用0.2 MPa压力的高压氧恢复60 min。安静对照组自由喂养,不进行训练。递增负荷训练组末次运动后1 h、高压氧舱恢复组恢复1 h及相应安静对照组分批麻醉处死,快速取腓肠肌立即用体积分数为0.1甲醛固定,制作切片。 主要观察指标：①苏木精-伊红染色观察各组大鼠骨骼肌细胞凋亡情况。②免疫组织化学检测各组大鼠骨骼肌细胞P53与Bcl-2蛋白表达情况。 结果：24只大鼠进入结果分析。①递增负荷训练组大鼠骨骼肌细胞凋亡数量增多,经高压氧恢复后细胞凋亡数量减少。②递增负荷训练组大鼠骨骼肌细胞P53蛋白表达增多,经高压氧恢复后表达显著减少。③递增负荷训练组大鼠骨骼肌细胞Bcl-2蛋白表达增多,高压氧恢复后未见减少。 结论：高压氧能够抑制递增负荷训练大鼠骨骼肌P53蛋白的表达,减少运动导致的大鼠骨骼肌细胞凋亡的发生。     

铁对大鼠黑质神经递质影响的初步研究

目的:探讨Fe3+/Fe2+对大鼠黑质神经递质影响。方法:黑质内分别注射:FeCl3、FeCl2和6-羟多巴胺(6-OHDA),四周后应用阿朴吗啡诱发旋转行为、高压液相色谱分析检测黑质内多巴胺、去甲肾上腺素、肾上腺素和5-羟色胺水平。结果:注射FeCl3的大鼠出现向损毁同侧的旋转行为;注射FeCl3和FeCl2侧黑质内多巴胺水平显著降低,去甲肾上腺素、肾上腺素和5-羟色胺水平不受影响。结论:Fe3+/Fe2+对大鼠黑质多巴胺能神经元具有特异性的毒性作用。     

不同训练负荷条件下SD大鼠运动模型的构建与评价

背景：目前对运动训练中机体能量代谢的研究多集中于骨骼肌线粒体生物发生及线粒体氧自由基等各指标的变化,不同训练负荷条件下身体能量代谢的系统的机制研究较少。 目的：建立SD大鼠有氧、无氧及有氧无氧代谢交叉训练运动模型,评价各组SD大鼠能量代谢水平指标的变化。 方法：实验建立有氧、无氧、有氧和无氧交替运动SD大鼠跑台运动训练模型,有氧运动时采用递增负荷训练,无氧运动时采用高速间歇训练,并设立正常对照组。测量运动后大鼠体质量减轻程度的变化,检测运动后大鼠血清中乳酸、乳酸脱氢酶、肌酐、尿素氮、肌酸激酶、丙酮酸激酶和琥珀酸脱氢酶的活性。 结果与结论：实验结果显示无氧组体质量减轻程度明显(P < 0.05),乳酸水平增高(P < 0.05),琥珀酸脱氢酶水平低于有氧组(P < 0.05);无氧组和交替运动组乳酸脱氢酶水平均增高(P < 0.05);运动后大鼠尿素氮水平增高非常显著(P < 0.001);交替组肌酸激酶、肌酐水平显著增高(P < 0.01),丙酮酸激酶水平增高(P < 0.05)。结果表明运动后大鼠代谢水平符合有氧、无氧、有氧和无氧交替运动的代谢评价,运动模型构建成功。     

无氧间歇训练对大鼠骨骼肌、心肌、肝脏自由基代谢的影响

背景：无氧间歇训练法是一种被广泛应用的重要训练方法，有关此训练对机体自由基代谢及其抗氧化酶活性影响的系统性研究较少。 目的：观察无氧间歇训练对大鼠体内自由基代谢的影响。 设计、时间及地点：随机对照动物实验，于2008-03/05在徐州师范大学运动生理实验室完成。 材料：健康雄性SD大鼠32只，体质量230~270 g，随机分为安静对照组，间歇训练对照组，间歇运动即刻组，间歇训练即刻组，每组8只。 方法：安静对照组不进行训练，间歇训练对照组和间歇训练即刻组进行跑步运动，以坡度10°，速度26.8 m/min运动1 min，后以坡度为0，速度5 m/min休息3 min，每天连续20次不间断，5 d/周，运动6周。间歇运动即刻组只在第6周最后一天进行一次运动。 主要观察指标：6周运动结束后即刻麻醉下处死各组大鼠，测定其骨骼肌，心肌，肝脏超氧化物歧化化酶，谷胱甘肽过氧化物酶，过氧化氢酶，丙二醛。 结果：①训练组运动后即刻各组织超氧化物歧化酶活性均显著高于间歇运动即刻组(P < 0.05)。②间歇运动即刻组股四头肌、心肌谷胱甘肽过氧化物酶活性显著低于安静对照组(P < 0.05)，丙二醛含量显著高于安静对照组(P < 0.05)，股四头肌和肝脏过氧化氢酶活性显著高于安静对照组(P < 0.05)。③间歇训练即刻组股四头肌、心肌谷胱甘肽过氧化物酶活性显著高于间歇运动即刻组(P < 0.05)，丙二醛含量明显低于间歇运动即刻组(P < 0.05)，股四头肌和心肌过氧化氢酶活性显著高于间歇运动即刻组(P < 0.05)。 结论：无氧间歇训练可以使机体抗氧化酶活性发生适应性变化，自由基清除能力增强。     

雌性大鼠雌激素和骨密度变化对长期中小强度游泳运动的影响

背景：有研究表明长期进行有氧运动可以引起女性雌激素和骨质成分的改变，但其机制不明。 目的：观察长期中小强度游泳运动对SD雌性大鼠雌激素及骨密度的影响。 方法：将SD大鼠随机分成对照组，游泳组Ⅰ和Ⅱ，两个游泳组从第1周开始均采用递增负荷游泳运动模式，游泳组Ⅰ以每次运动60 min的负荷游泳4周；游泳组Ⅱ以每次运动60 min的负荷游泳7周。对照组不做任何训练干预。两个游泳组每次游泳1 h后，均用电子显微镜动态观察大鼠阴道脱落细胞的数量和形态变化。训练结束后，用放射免疫法测定各组大鼠的雌激素水平，用双能X射线骨密度吸收仪测骨密度。 结果与结论：与对照组比较，游泳组Ⅱ大鼠阴道底层细胞的数量逐周增多，第7周最多(P < 0.01)。游泳组Ⅱ大鼠血清雌二醇、孕酮和血睾酮明显升高 (P < 0.01)。游泳组Ⅰ腰椎及股骨的骨密度均高于对照组 (P < 0.05)。游泳组Ⅱ的腰椎及股骨的骨密度均高于游泳组Ⅰ(P < 0.05，P < 0.01)。结果提示，长期中小负荷游泳运动可提高大鼠的骨密度和雌激素水平。     

骨量及骨代谢中胰岛素生长因子1、转化生长因子β和白细胞介素6在长期递增负荷运动状态下的变化*☆

背景：研究表明,合理的适量运动能够促进骨量,相反过量运动会影响骨量的蓄积,但负荷过量的运动对骨代谢的影响作用机制目前仍不清楚。 目的：探讨长期递增负荷运动对骨量的影响效应,以及对骨代谢的影响作用机制。 方法：将SD大鼠分别进行4,9,11,13,15,17周的递增负荷运动,并设置对照组,以放射免疫分析法测定各组大鼠雌二醇水平,以酶联免疫法测定各组血清胰岛素生长因子1,转化生长因子β及白细胞介素6的浓度,以双能X射线骨密度仪测定各组骨密度水平。 结果与结论：和同期对照组相比,胰岛素生长因子1和转化生长因子β在运动后9和17周显著降低(P < 0.05),转化生长因子β在运动第4周显著升高(P < 0.05),白细胞介素6在运动第9,15,17周均显著升高(P < 0.05)。雌二醇水平在运动第13,15和17周降低(P < 0.05或P < 0.01),全身骨密度值在运动第15,17周显著降低(P < 0.01)。结果证实,长期递增负荷运动导致大鼠机体骨代谢发生改变,由骨形成占优势过渡为骨吸收占优势,最终出现骨密度值降低,骨代谢平衡向破骨方向倾斜的重要致因与过量运动所造成的性腺轴功能受抑,雌二醇水平降低有关。     

帕金森氏病患者丘脑腹外侧核毁损术后脑脊液中单胺类递质含量的变化

目的：观察帕金森氏病患者脑立体定向术前、后脑脊液中神经递质水平的变化，这种变化的作用机理如何。方法：对１５例帕金森氏病患者丘脑腹外侧核毁损术前及术后一周脑脊液中单胺类递质水平检测及手术疗效观察。结果：患者术后脑脊液中多巴胺水平与术前无显著差异，而５－羟色胺、去甲肾上腺素、５－羟吲哚乙酸显著减少，术后毁损区对侧上下肢体震颤、肌强直消失，但运动不能症状未能改善。结论：帕金森氏病术后中枢多种神经递质发生改变并在低水平下暂时获得平衡。从中枢神经递质生化变化，脑立体定向术不能彻底治愈帕金森氏病     

耐力运动大鼠跟腱胶原、基质金属蛋白酶1及其抑制剂1的表达

背景：胶原是肌腱细胞外基质中的主要成分,基质金属蛋白酶是降解肌腱细胞外基质蛋白的重要蛋白酶。 目的：观察12周跑台运动对大鼠跟腱胶原、胶原Ⅰ、基质金属蛋白酶1及其抑制剂1表达的影响。 方法：将20只雄性SD大鼠随机分为对照组和运动组。第1周每天运动20 min,速度由12 m/min递增至20 m/min;以后跑台速度均为20 m/min,第2周坡度为5%,时间为30 min,第3~12周坡度为10%,时间为40 min,共运动12周。对照组正常饲养。 结果与结论：末次运动后24 h取大鼠跟腱。与对照组比较,运动组大鼠跟腱前胶原Ⅰα1、基质金属蛋白酶1及其抑制剂1 mRNA的表达明显升高(P < 0.05或P < 0.01),羟脯氨酸的含量也有所增多,但与对照组比较差异无显著性意义(P > 0.05)。表明长期耐力运动可以提高跟腱中胶原的合成和降解能力。     

降钙素基因相关肽神经生长因子与失神经支配兔骨折愈合

背景：骨折不愈合严重影响患者生活质量,神经生长因子用于骨不连的防治是重建外科领域研究的重点和方向。 目的：观察神经生长因子降钙素基因相关肽对失神经支配兔骨折愈合的影响。 方法：构建大白兔失神经支配腓骨骨折模型后,实验组骨折端局部注射降钙素基因相关肽10 μg,每2 d一次;对照组骨折端局部注射等量生理盐水。术后2,4,6周分别测定静脉血中肾上腺素和去甲肾上腺素的水平,并进行生物力学和组织学分析。 结果与结论：术后两组血清肾上腺素和去甲肾上腺素水平均有显著增高,在术后第4周达到最高峰,比术前高出1倍以上,第6周时出现下降,但仍然显著高于术前;术后2,4,6周,实验组肾上腺素和去甲肾上腺素血清水平较对照组显著增高,差异具有显著性意义(P < 0.05~0.01)。在三点弯曲实验中,实验组骨痂的抗弯强度明显高于对照组(P < 0.05~0.001);术后第6周时苏木精-伊红染色可见实验组骨痂中的透明软骨细胞已被成骨细胞替代,对照组骨痂中的软骨细胞仍没有完全成骨细胞化。提示神经生长因子降钙素基因相关肽对失神经支配兔骨折愈合具有明显的促进作用。 关键词：神经生长因子;降钙素基因相关肽;骨折愈合;生物力学;生物化学     

大网膜脊髓移植治疗急性脊髓损伤的神经生化和运动功能实验研究

带蒂大网膜移植于兔损伤的脊髓,观察脊髓组织中5-羟色胺、去甲肾上腺素和多巴胺含量的改变,并观察脊髓运动功能恢复情况。实验显示大网膜脊髓移植可以早期吸收脊髓损伤后异常升高的五羟色胺和去甲肾上腺素。大网膜移植组动物运动功能恢复显著优于损伤组。作者认为大网膜的吸收功能在治疗急性脊髓损伤中可能有一定的作用。     

Indoleamine and catecholamine concentrations in the mid-term human fetal brain

Because of the likelihood that androgen-induced sex specific brain differentiation is mediated by various neurotransmitters, their concentrations were measured in the mid-term human fetal hypothalamus, cortex and cerebrospinal fluid (CSF). Tissue was collected from 32 hysterotomy specimens aged from 10 to 23 weeks, immediately frozen in liquid nitrogen, and stored at -20 degrees C. 5-Hydroxytryptamine (5-HT), 5-hydroxy indole acetic acid (5-HIAA), norepinephrine (NE) and dopamine (DA) levels were measured by a fluorometric assay. Cord serum testosterone levels were measured by radioimmunoassay. In the male fetuses, hypothalamic concentrations of 5-HT, 5-HIAA and NE were all significantly increased in comparison to those in the cortex. Because the number of female fetuses was small, only the 5-HIAA levels were seen to be significantly higher in the hypothalamus than in the cortex. In the CSF from fetuses of both sexes, the DA levels were greatly raised. Concentrations of NE were significantly higher in male fetuses aged from 14-16 weeks, a time when plasma testosterone levels are also elevated. It is hypothesized that the raised plasma testosterone and hypothalamic NE concentrations are inter-related.     

The effect of S. pneumoniae bacteremia on cerebral blood flow autoregulation in rats.

In the present study, we studied the effect of bacteremia on cerebral blood flow (CBF) autoregulation in a rat model of pneumococcal bacteremia and meningitis. Anesthetized rats were divided into five groups (A to E) and inoculated with pneumococci intravenously and normal saline intracisternally (group A, N=10); saline intravenously and pneumococci intracisternally (group B, N=10); pneumococci intravenously and pneumococci intracisternally (group C, N=5); saline intravenously, antipneumococcal antibody intravenously (to prevent bacteremia), and pneumococci intracisternally (group D, N=10); or saline intravenously and saline intracisternally (group E, N=10), respectively. Positive cultures occurred in the blood for all rats in groups A, B, and C, and in the cerebrospinal fluid for all rats in groups D and E. Twenty-four hours after inoculation, CBF was measured with laser-Doppler ultrasound during incremental reductions in cerebral perfusion pressure (CPP) by controlled hemorrhage. Autoregulation was preserved in all rats without meningitis (groups A and E) and was lost in 24 of 25 meningitis rats (groups B, C, and D) (P<0.01). In group A, the lower limit was higher than that of group E (P<0.05). The slope of the CBF/CPP regression line differed between the meningitis groups (P<0.001), being steeper for group B than groups C and D, with no difference between these two groups. The results suggest that pneumococcal bacteremia in rats triggers cerebral vasodilation, which right shifts the lower limit of, but does not entirely abolish, CBF autoregulation in the absence of meningitis, and which may further aggravate the vasoparalysis induced by concomitant pneumococcal meningitis.     

Effects of blinding and pinealectomy on regional brain monoamine concentrations

The effects of blinding with or without pineal ablation on brain monoamine levels were studied in male rats. Brain dopamine (DA), norepinephrine (NE), epinephrine (E), and serotonin (5-HT) were measured by radioenzymatic assays. Four weeks following pinealectomy, E levels were significantly enhanced in the frontal cortex. Chronic blinding decreased striatal DA levels and increased striatal 5-HT levels in both sham-operated and pinealectomized (Px) animals. In a second experiment Px animals were sacrificed 1 or 7 d after pinealectomy in order to examine the short-term effects of pinealectomy. There were no differences between controls and Px animals in their cortical levels of DA, NE, and E and their hippocampal and hypothalamic 5-HT levels. However, the E concentrations measured 1 d after surgery were significantly greater than after 7 d. The implications of these findings with regard to the reported role of the pineal and melatonin in brain homeostasis and endocrine regulation are discussed.     

Effect of treadmill exercise on 5-HT, 5-HT1A receptor and brain derived neurophic factor in rats after permanent middle cerebral artery occlusion

It has been well documented that exercise promotes neurological rehabilitation in patients with cerebral ischemia. However, the exact mechanisms have not been fully elucidated. This study aimed to discuss the effect of treadmill exercise on expression levels of 5-HT, 5-HT1A receptor (5-HT1AR) and brain derived neurophic factor (BDNF) in rat brains after permanent middle cerebral artery occlusion (pMCAO). A total of 55 rats were randomly divided into 3 groups: pMCAO group, pMCAO and treadmill exercise (pMCAO + Ex) group, and sham-operated group. Rats in pMCAO + Ex group underwent treadmill exercise for 16 days. Neurological function was evaluated by modified Neurological Severity Scores (mNSS). High-performance liquid chromatography-electrochemical detection system was used to determine the content of 5-HT in cortex tissues. The protein levels of 5-HT1AR, BDNF and synaptophysin were measured by Western blot. The mNSS in pMCAO + Ex group was lower than that in pMCAO group on day 19 post-MCAO (p < 0.001). The content of 5-HT dropped to 3.81 ± 1.86 ng/ml in pMCAO group (43.84 ± 2.05 ng/ml in sham-operated group), but increased in pMCAO + Ex group (10.06 ± 1.80 ng/ml). The protein expressions levels of synaptophysin, 5-HT1AR and BDNF were downregulated after cerebral ischemia (p < 0.05), and upregulated after treadmill exercise (p < 0.05). These results indicate that treadmill exercise improves neurologic function, enhances neuronal plasticity and upregulates the levels of 5-HT, 5-HT1AR and BDNF in rats with pMCAO.     

帕金森病外科治疗的综合评价与相关基础研究

目的通过综合研究对帕金森病(PD)外科治疗的价值和疗效进行全面评价。方法采用医学心理学测验(WAISRC)、临床记忆量表(MMPI)、神经生理学检测(听觉P300地形图)、神经电生理学(体感诱发电位SEP)和神经生化检查的脑脊液中多巴胺(DA)、5羟色胺(5HT)、去甲肾上腺素(NE)及其代谢产物)等对手术前后患者进行综合研究,并设对照组。结果手术前后智能和精神症状无显著性差异(P>0.05);手术后SEP的N20波峰潜伏期较术前缩短,统计学处理有差异(P左<0.005,P右<0.05),手术侧较非手术侧峰潜伏期缩短(P<0.05)。伴发抑郁患者组CSF中单胺类神经递质5HT的代谢产物5羟吲哚乙酸(5HIAA)和NE的代谢产物3甲氧基4羟基苯乙二醇(MHPG)低于对照组(P<0.01),患者组DA、高香草酸(HVA),5HT,5HIAA、NE、MPHG低于正常对照组(P<0.001),手术组上述各项均高于手术前组(P<0.001);结论手术不会加重智能和精神障碍;听觉P300地形图可作为诊断和疗效判定的客观指标之一;帕金森病及伴发抑郁症状均具有相应生化病理学基础。     

Influences of cholecystokinin antiserum on the dopamine,norepinephrine and serotonin contents of different brain regions in rats

The effects of intraventricular administration of cholecystokinin antiserum on the dopamine (DA), norepinephrine (NE) and serotonin (5-HT) contents of the hypothalamus, mesencephalon, amygdala, septum, striatum and cerebral cortex were tested 24 hr following injection in rats.Cholecystokinin antiserum decreased the DA and NE contents of the hypothalamus, mesencephalon, amygdala and septum, while it increased the DA and decreased the NE content of the striatum. In the cerebral cortex the NE content was decreased. The 5-HT contents decreased in the mesencephalon, amygdala and septum, and increased in the striatum.     

人工脑脊液冲洗治疗对实验性大鼠脑外伤后低氧诱导因子表达的影响

目的探讨人工脑脊液局灶冲洗治疗对实验性大鼠创伤性脑损伤后脑水肿及低氧诱导因子-1α(HIF-1α)表达的影响。方法采用自由落体打击装置制备大鼠创伤性脑损伤模型,分正常对照组、外伤对照组、生理盐水冲洗治疗组及人工脑脊液冲洗治疗组。于伤后30min开始分别以37℃的生理盐水和人工脑脊液进行局灶冲洗治疗维持3h。伤后4h、1、3、5、7d处死留取脑组织标本,采用干湿重法测伤灶脑组织含水量,RT-PCR方法检测HIF-1αmRNA的表达。结果与外伤对照组相比,生理盐水和人工脑脊液治疗组伤灶脑组织水含量明显降低(P<0.05);脑外伤后4h伤灶脑组织中HIF-1αmRNA表达即明显上升,1d达到高峰,持续至3d,5d开始下降,7d降至正常水平;局灶冲洗治疗后,伤后4h、1d、3d和5d各组脑组织HIF-1αmRNA表达均低于外伤对照组相应各时间点(P<0.05);其中以局灶人工脑脊液冲洗治疗效果最佳。结论局灶人工脑脊液冲洗治疗能明显减轻大鼠伤灶脑水肿,有良好的治疗作用;调节HIF-1α的表达是其脑保护作用的机制之一。     

Increased 5-HT2C receptor binding in the brain stem and cerebral cortex during liver regeneration and hepatic neoplasia in rats

In the present study, serotonin 2C (5-HT(2C)) receptor binding parameters in the brainstem and cerebral cortex were investigated during liver generation after partial hepatectomy (PH) and N-nitrosodiethylamine (NDEA) induced hepatic neoplasia in male Wistar rats. The serotonin content increased significantly (p<0.01) in the cerebral cortex after PH and in NDEA induced hepatic neoplasia. Brain stem serotonin content increased significantly (p<0.05) after PH and (p<0.001) in NDEA induced hepatic neoplasia. The number and affinity of the 5-HT(2C) receptors in the crude synaptic membrane preparations of the brain stem showed a significant (p<0.001) increase after PH and in NDEA induced hepatic neoplasia. The number and affinity of 5-HT(2C) receptors increased significantly (p<0.001) in NDEA induced hepatic neoplasia in the crude synaptic membrane preparations of the cerebral cortex. There was a significant (p<0.01) increase in plasma norepinephrine in PH and (p<0.001) in NDEA induced hepatic neoplasia, indicating sympathetic stimulation. Thus, our results suggest that during active hepatocyte proliferation 5-HT(2C) receptor in the brain stem and cerebral cortex are up-regulated which in turn induce hepatocyte proliferation mediated through sympathetic stimulation.     

帕罗西汀与阿米替林联用对卒中后抑郁大鼠额前皮质区与海马区的单胺类递质、脑源性神经营养因子水平的改变

目的探究帕罗西汀与阿米替林联用对脑卒中后抑郁(post-stroke depression,PSD)大鼠额前皮质区与海马区的单胺类递质、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)水平的影响.方法SD大鼠被分为4组,即对照组、PSD组、帕罗西汀(Par)组和帕罗西汀+阿米替林(Par+Ami)组.通过"线栓法"和慢性不可预见性温和刺激建立PSD大鼠模型.Par组灌胃给予帕罗西汀1.8 mg·kg^-1,Par+Ami组在Par基础上腹腔注射阿米替林10 mg·kg^-1,干预3w.分别在干预前、PSD建模后和干预后检测大鼠体质量、停止游泳的时间和蔗糖偏爱度.在干预后分别通过酶联免疫吸附实验、qPCR和Western blot检测额叶皮质和海马体5-羟色胺(5-hydroxytryptamine,5-HT)、去甲肾上腺素(norepinephrine,NE)、多巴胺(dopamine,DA)以及BDNF mRNA和蛋白的水平.结果建模前各组大鼠体质量、行为学指标、皮质和海马体5-HT、NE、DA以及BDNF mRNA和蛋白的水平比较差异均无统计学意义(P>0.05).建模后大鼠的体质量和蔗糖偏爱度显著降低,停止游泳的时间显著升高(P<0.05).干预后PSD组大鼠的体质量、蔗糖偏爱度、质和海马体5-HT、NE、DA以及BDNF mRNA和蛋白的水平显著低于对照组,停止游泳的时间显著高于对照组(P<0.05).Par组和Par+Ami组的大鼠的体质量、蔗糖偏爱度、质和海马体5-HT、NE、DA以及BDNF mRNA和蛋白的水平显著高于PSD组,停止游泳的时间显著低于PSD组(P<0.05).并且Par+Ami组的大鼠的体质量、蔗糖偏爱度、质和海马体5-HT、NE、DA以及BDNF mRNA和蛋白的水平显著高于Par组,停止游泳的时间显著低于Par组(P<0.05).结论帕罗西汀联合阿米替林可更有效的提高皮质和海马体中5-HT等单胺类神经递质的水平,缓解PSD大鼠模型的抑郁程度,并且可促进BDNF的水平,改善神经功能,提高对PSD的疗效和预后.     

A distinct neurochemical profile in WKY rats at baseline and in response to acute stress: implications for animal models of anxiety and depression

Wistar-Kyoto (WKY) rats exhibit hyperresponsive neuroendocrine and behavioral responses to stress that exceed normal controls and are especially prone to develop stress-induced depressive disorder. Pharmacological studies indicate altered serotonin (5-HT), norepinephrine (NE) and dopamine (DA) systems functioning in WKY rats, yet no attempt has been made to provide a comprehensive assessment of the neurochemical profile for WKY rats as compared to the outbred progenitor controls, Wistar rats. To this end, male, WKY and Wistar rats (N=6/group) were exposed to an acute forced-swim stress or were left untreated as controls. The prefrontal cortex (PFCtx), striatum, nucleus accumbens (NAS), and amygdala were assayed for levels of NE, DA and 5-HT, as well as major metabolites, by high-pressure liquid chromatography (HPLC) with electrochemical detection. In a separate experiment, designed to assess baseline and stress-induced neuroendocrine activation, male, Wistar and WKY rats (N=6/group) were exposed to an acute forced-swim stress of 15 min or were left untreated as controls. Animals were killed immediately after the test (T=0), 30 min after the test (T=30) or 60 min after the test (T=60), and control animals were killed immediately after weighing. After decapitation, trunk blood was collected and plasma was isolated by centrifugation and analyzed for corticosterone by immunoassay. The neurochemical results demonstrate distinct patterns of baseline and stress-induced monoamine turnover in WKY rats, including alterations to DA and 5-HT turnovers in prefrontal cortex and nucleus accumbens, two critical brain areas implicated in anxiety, depression and drug reward. The neuroendocrine results indicate that WKY rats exhibited a sustained corticosterone response to acute stress, as compared to Wistar controls. Overall, these data are predicted to be useful for understanding the anxiety- and depressive-like behavioral phenotype exhibited by these animals and for increased understanding of the role genetic background in altering neurochemical function.