二甲双胍对慢性应激大鼠抑郁行为的影响

目的:观察二甲双胍对慢性不可预测性温和应激大鼠抑郁行为的影响。方法:40只雄性SD大鼠随机分为4组(n=10):对照组(CON组)、二甲双胍组(MET组)、模型组(CUMS组)、模型+二甲双胍组(CUMS+MET组),采用慢性不可预测性温和应激(CUMS)方法,用3周时间建立大鼠抑郁模型。造模完成后,两个二甲双胍组腹腔注射二甲双胍(100mg/kg),对照组和模型组注射等量的生理盐水,每天1次,连续2周。之后检测大鼠体重增长变化、糖水嗜好、强迫游泳和悬尾不动实验、旷场实验等大鼠行为学的改变,采用尼氏染色观察大鼠海马形态结构变化。结果:与对照组比较,CUMS组大鼠体重增长明显减慢(P<0.05),糖水偏爱率明显降低(P<0.05),强迫游泳和悬尾不动实验中不动时间明显延长(P<0.05),旷场实验中自发活动明显减少(P<0.05),大鼠海马的形态结构有所变化,证实CUMS抑郁模型建立成功。与CUMS组比较,二甲双胍处理后对大鼠的体重无明显影响,但能明显改善CUMS抑郁模型大鼠的糖水摄入、不动时间和自发活动(P<0.05),并能修复CUMS大鼠海马的异常形态结构变化。结论:二甲双胍对CUMS诱导的大鼠抑郁行为具有明显的改善作用,为临床糖尿病并发抑郁症的患者提供新的治疗手段。     

杏仁核SIRT1对慢性束缚应激大鼠抑郁样行为的影响

目的:观察杏仁核沉默信息调节因子1(SIRT1)蛋白对慢性束缚应激(CRS)大鼠抑郁样行为的影响。方法:60只SD雄性大鼠随机分为6组(n=10):正常对照组(Control)、慢性束缚应激组(CRS)、CRS+氟西汀(FLU)组(CRS+FLU)、CRS+生理盐水组(CRS+NaCl)、CRS+SIRT1过表达组(CRS+AAV-SIRT1)和CRS+空载体组(CRS+AAV-EGFP)。除了正常对照组,其余各组均接受慢性束缚应激造模21 d。造模结束后,氟西汀组和生理盐水组大鼠每天分别灌胃给予氟西汀(10 mg/kg)或生理盐水(10 mg/kg),持续3周;SIRT1过表达组和空载体组大鼠分别脑立体定位,注射腺相关病毒AAV-SIRT1或AAV-EGFP于杏仁核,待病毒表达3周;正常组和抑郁症组大鼠则不给予任何药物。应用糖水偏好实验(SPT)、旷场实验(OFT)和强迫游泳实验(FST)检测各组大鼠的抑郁样行为学变化;蛋白免疫印迹实验检测大鼠杏仁核中SIRT1蛋白的表达;免疫荧光技术检测大鼠杏仁核中SIRT1阳性细胞数量。结果:与正常对照组相比,CRS抑郁大鼠杏仁核中SIRT1蛋白...     

黄酒对慢性应激大鼠肠道微生物的影响

目的 探讨黄酒对慢性应激大鼠肠道微生物的影响.方法 将45只SD大鼠制成慢性应激模型,并随机分为正常对照组、慢性应激对照组和慢性应激黄酒组.正常对照组、慢性应激对照组仅给予正常饲料喂食,慢性应激黄酒组饲料中每日添加酒精度为15.0％ (v/v)的黄酒5 mL,6周后处死大鼠,取肠道内容物做肠道乳酸菌、大肠埃希菌及真菌等微生物培养,数据采用统计学方法分析.结果 黄酒不影响大鼠的血糖变化,与正常对照组相比,慢性应激对照组乳酸菌明显减少,差异有统计学意义(P＜0.01),大肠埃希菌和真菌数量增加,差异亦有统计学意义(P＜0.05);慢性应激黄酒组乳酸菌增多,差异有统计学意义(P＜0.05),大肠埃希菌和真菌数量减少,比较差异亦有统计学意义(P＜0.05).结论 慢性应激状态下,肠道微生物发生明显的变化,适量饮用黄酒能增加肠道益生菌,减少肠道致病菌或条件致病菌,维持肠道微生态平衡,对肠道微生物有一定的调节作用.     

低聚果糖对慢性应激小鼠抑郁样行为及肠道菌群的影响

目的 探讨低聚果糖（FOS）对慢性应激小鼠的抑郁样行为及肠道菌群的影响。方法 选取8周龄健康雄性ICR小鼠随机分成3组,C组小鼠每天给予正常护理,S组和SF组小鼠每天随机给予1～2种应激源,持续8周,SF组小鼠在应激造模的同时经食物补充FOS。在造模4周和8周后,分别通过强迫游泳、蔗糖偏好试验评估各组小鼠抑郁样行为。造模结束后通过Western blot试验检测小鼠大脑皮层内糖皮质激素受体（GR）的表达,并收集结肠内容物进行16S rDNA扩增子测序分析。结果 应激造模8周后,C、S和SF三组小鼠的肠道菌群组成存在明显差异;与C组相比,S组小鼠强迫游泳的不动时间显著增加（t=3.970,P=0.0009）,蔗糖偏好率显著降低（t=3.890,P=0.0011）,脑内GR的表达显著降低（t=4.311,P=0.0125）;与S组相比,SF组小鼠强迫游泳的不动时间显著缩短（t=3.495,P=0.0026）,蔗糖偏好率和脑内GR表达有增加趋势。结论 益生元FOS可调节肠道菌群,改善慢性应激诱发的精神情绪异常。     

逍遥散对慢性束缚应激模型大鼠相关脑区CRF基因表达的影响

目的:观察慢性束缚应激大鼠相关脑区CRF mRNA(下丘脑、垂体、海马、皮层)含量变化以及逍遥散对其影响.方法:用RT-PCR和图像分析方法测定相关脑区CRF mRNA含量变化.结果:应激组较正常对照组在下丘脑CRF-1基因表达下调(P<0.01).在下丘脑逍遥散组较应激组CRF-1基因表达显著下调(P<0.01),CRF-2基因表达显著上调(P<0.01);在海马区逍遥散组CRF-2基因表达较模型组上调(P<0.05);在皮层逍遥散组CRF-1基因表达较应激组则显著上调(P<0.01).结论:逍遥散组对慢性束缚应激中枢神经肽CRF的调节位点在下丘脑、垂体、海马和皮层,充分证实逍遥散的调节靶点与下丘脑、边缘系统及皮层中枢有关.     

慢性复合应激对大鼠胰腺HAP1表达的影响

目的探讨慢性复合应激大鼠胰腺内胰岛内分泌细胞HAP1表达的变化及其意义。方法36只大鼠随机分为两组:慢性复合应激组和正常对照组。应激组动物无规律交替暴露于垂直旋转、睡眠剥夺、捆绑(6h/d)和夜间光照等慢性复合性应激,共6周;实验结束后,采用免疫组织化学和Western-blot等方法检测两组大鼠胰腺胰岛内分泌细胞内HAP1蛋白表达的变化。结果HAP1在大鼠胰腺内选择性表达于胰岛内分泌细胞中。与对照组相比,慢性复合应激组大鼠胰腺HAP1的表达明显增强(P<0.05)。结论6周慢性复合性应激可使大鼠胰腺中胰岛内分泌细胞的HAP1表达加强,提示HAP-1在慢性复合应激促进胰腺内分泌功能中可能发挥一定作用。     

天麻素对CUS大鼠抑郁样行为和海马BDNF/GDNF水平的影响

目的:探讨天麻素对慢性不可预见应激(CUS)大鼠抑郁样行为的改善作用及对海马脑源性神经营养因子(BDNF)及胶质原纤维酸性蛋白(GDNF)表达的影响。方法:将64只SD大鼠随机分为对照组(Sham),Sham+天麻素低、中、高剂量组,模型组(CUS),模型(CUS)+天麻素低、中、高剂量组,每组8只。对照组每天腹腔注射生理盐水(1 m L/kg),连续14天;Sham+天麻素低、中、高剂量组每天腹腔注射不同剂量的天麻素(50、100或者200 mg/kg),连续14天;模型组接受CUS造模,并且在造模结束后每天腹腔注射生理盐水(1 m L/kg),连续14天;模型+天麻素低、中、高剂量组在CUS造模结束后每天腹腔注射不同剂量的天麻素(50、100或者200 mg/kg),持续14天。随后,通过糖水偏好实验和强迫游泳实验检测各组大鼠的抑郁样行为,在行为学检测结束后处死大鼠,通过Elisa检测海马GFAP和BDNF的表达情况。结果:(1)慢性不可预见应激(CUS)可以导致明显的抑郁样行为,包括糖水偏好减少(P0.05)和强迫游泳不动时间增加(P0.01),CUS组大鼠海马GFAP和BDNF水平下降(P0.01)。(2)一定剂量(100和200 mg/Kg)天麻素干预可以缓解CUS大鼠的抑郁行为,CUS与CUS+GAS(M)组(P0.05)以及CUS与CUS+GAS(H)组之间(P0.01)存在显著性差异。(3)中高剂量的天麻素可以恢复CUS大鼠海马的BDNF和GDNF水平,CUS与CUS+GAS(M)组(P0.05)以及CUS与CUS+GAS(H)组之间(P0.05)的BDNF和GDNF水平存在显著性差异。结论:天麻素可以缓解CUS模型大鼠抑郁样行为,恢复CUS模型大鼠海马的BDNF和GDNF水平。     

HAP-1在慢性复合应激大鼠肾上腺的表达

目的探讨慢性复合应激大鼠肾上腺髓质细胞亨廷顿蛋白相关蛋白1(Huntingtin-associated protein 1,HAP-1)表达的变化及其意义。方法36只大鼠随机分为两组:慢性复合应激组和对照组。应激组动物进行6周的垂直旋转、睡眠剥夺、捆绑(6h/d)和夜间光照等慢性复合性应激试验;实验结束后,所有动物采用免疫组织化学、Western-blot以及RT-PCR等方法检测肾上腺髓质细胞内HAP-1蛋白和mRNA水平的变化。结果与对照组相比,慢性复合应激组的大鼠肾上腺髓质中HAP-1的表达明显增强(P<0.05),HAP-1 mRNA水平明显升高(P<0.05)。结论6周慢性复合性应激大鼠HAP-1在肾上腺髓质区的表达加强,mRNA水平提高。提示HAP-1在慢性复合应激促进肾上腺功能中可能发挥一定作用。     

不同时程束缚水浸应激对大鼠胃排空的影响

目的研究不同时程慢性束缚水浸应激对大鼠胃排空的影响。方法48只雄性150 g左右SD大鼠被随机分为6组,即实验3、72、8 d组和对照3、72、8 d组,每组8只。实验期间,每日观察大鼠体重、一般状况及行为学指标。实验组23℃水域箱内束缚水浸1 h/d,对照组自由摄食饮水。采用半固体排空实验（阿拉伯胶炭糊）来检测胃排空率,数据录入SPSS 13.0进行分析处理。结果①体重增加情况：不同组别和不同应激时间这两个因素对体重增加的影响差异均有显著性。②胃排空率：对照各组间比较均无统计学差异。3 d组间（实验3d组与对照3 d组）大鼠胃排空率无差异;而7 d组间和28 d组间比较则明显异常。随着应激时间的延长,实验组胃排空率呈现了先增高（7 d时）后降低（28 d）的变化趋势,且实验3 d组与7 d组、7 d组与28 d组间比较均有明显的统计学意义,而3 d组与28 d组比较则无统计学差异。结论不同时程的慢性束缚水浸应激可以导致大鼠胃排空率改变;随着应激时间的延长,呈现先上升后下降的规律。     

大鼠眶额叶GABA及其B型受体在应激性抑郁行为发生中的作用及其影响机制

为了探讨眶额叶(orbital frontal cortex,OFC)GABA及其B型受体在应激性抑郁行为发生中的作用及其影响机制,实验采用强迫游泳方法建立急性应激抑郁模型。在OFC区微量注射γ-氨基丁酸(γ-aminobutyric acid,GABA)及其B型受体阻断剂,通过开场实验、强迫游泳方式检测动物行为学表现,用免疫组织化学染色和Western blotting方法检测OFC区Kalirin表达,用高尔基染色法观察锥体细胞树突和树突棘。结果显示:强迫游泳应激引起动物抑郁样行为表现,同时,OFC区Kalirin阳性颗粒数及表达量显著减少,且锥体细胞树突棘密度下降;OFC区微量注射GABA具有抗抑郁效应,使OFC区Kalirin表达显著升高,锥体细胞树突棘密度增加;GABA-B型受体阻断剂CGP35348可以抑制GABA的这种效应。由此可见,通过强迫游泳应激诱发的抑郁样的行为变化与OFC区Kalirin表达减少和神经元树突棘密度降低有关,GABA可能通过GABA-B型受体增加OFC区Kalirin表达,以防止神经元退行性变化而产生抗抑郁作用。     

Age-dependent effects of chronic stress on brain plasticity and depressive behavior

Exposure to chronic mild stress (CMS) is known to induce anhedonia in adult animals, and is associated with induction of depression in humans. However, the behavioral effects of CMS in young animals have not yet been characterized, and little is known about the long-term neurochemical effects of CMS in either young or adult animals. Here, we found that CMS induces anhedonia in adult but not in young animals, as measured by a set of behavioral paradigms. Furthermore, while CMS decreased neurogenesis and levels of brain-derived neurotrophic factor (BDNF) in the hippocampus of adult animals, it increased these parameters in young animals. We also found that CMS altered alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor GluR1 subunit levels in the hippocampus and the nucleus accumbens of adult, but not young animals. Finally, no significant differences were observed between the effects of CMS on circadian corticosterone levels in the different age groups. The substantially different neurochemical effects chronic stress exerts in young and adult animals may explain the behavioral resilience to such stress young animals possess.     

慢性不可预见性应激对大鼠恐惧条件反射和躯体感觉诱发电位的影响

目的:探讨慢性不可预见性应激对大鼠恐惧条件反射以及体感诱发电位的影响并分析可能的神经电生理机制。方法:26只雄性SD大鼠(190~200 g)随机分成两组(n=13):对照组和模型组。用慢性不可预见性应激刺激模型组大鼠,用恐惧条件反射实验检测两组大鼠的恐惧反应,用躯体感觉诱发电位检测大鼠脑电活动。结果:与对照组相比,模型组大鼠在恐惧记忆阶段不动时间百分比减小(56.64%±13.78%vs69.72%±18.10%,P<0.05),躯体感觉诱发电位的第二个正向波(P2)潜伏期也明显缩短(70.54±10.13 msvs78.46±7.80 ms,P<0.05)。相关性分析显示大鼠恐惧条件反射的不动时间与躯体感觉诱发电位潜伏期存在正相关(r=0.507,P<0.05)。结论:慢性不可预见性应激抑制大鼠恐惧反应,并缩短体表感觉诱发电位的潜伏期,恐惧反应行为与体感诱发电位潜伏期存在正相关,提示大鼠恐惧反应与体表感觉诱发电位可能有共同的神经递质机制。     

慢性应激不同方式对大鼠血清皮质酮的影响

目的：比较慢性应激不同方式对生理状态大鼠血清皮质酮水平的影响,研究机体慢性应激反应的整体性适应特征。方法：采用连续4周的适宜游泳、束缚和二者复合的三种应激方式后,测定大鼠血清皮质酮基础含量,分析不同慢性应激方式对皮质酮水平的影响。结果：血清皮质酮水平与对照组比较,复合组无显著性差异;游泳组虽升高但无显著性;束缚组升高有显著性意义。结论：束缚可致大鼠血清皮质酮水平增高;初步认定游泳与束缚复合慢性应激方式可能对机体的整体适应性能具有积极意义。     

推拿对失神经骨骼肌萎缩大鼠的治疗作用及其机制*

目的:探讨推拿对失神经骨骼肌萎缩大鼠的治疗作用及其机制。方法:48只雄性SD大鼠随机分为模型组(n=24)和推拿组(n=24),通过切断右侧胫神经制备腓肠肌萎缩大鼠模型。术后第2日开始给推拿组大鼠手术侧腓肠肌给予手法干预,模型组不予干预。两组分别在0 d、7 d、14 d、21 d四个时间点各处死6只大鼠,取大鼠双侧腓肠肌,称重后计算各组大鼠腓肠肌湿重比;HE染色测定肌纤维截面积和直径,实时荧光定量PCR检测腓肠肌中miR-23a、Akt、MuRF1、MAFbx基因相对表达量。结果:与0 d比较,模型组和推拿组大鼠腓肠肌湿重比、肌纤维截面积和直径呈现进行性下降的趋势,其中7 d、14 d、21 d推拿组腓肠肌湿重比、肌纤维截面积和直径均显著高于模型组(P＜0.05,P＜0.01);与0 d比较,模型组和推拿组MuRF1、MAFbx、Akt mRNA表达均呈现先升后降的趋势,其中7 d、21 d推拿组MuRF1 mRNA表达均显著低于模型组(P＜0.05,P＜0.01),7 d、14 d、21 d推拿组MAFbx mRNA表达均显著低于模型组(P＜0.01,P＜0.05,P＜0.01),7 d、14 d、21 d推拿组Akt mRNA表达均显著高于模型组(P＜0.05,P＜0.01);与0 d比较,模型组和推拿组21 d时miR-23a mRNA表达升高,推拿组miR-23a mRNA表达显著高于模型组(P＜0.05)。结论:推拿能延缓失神经骨骼肌的萎缩,其机制可能与上调miR-23a、Akt基因的表达,下调 MuRF1、MAFbx基因的表达,使蛋白降解速度受到抑制,从而减轻骨骼肌蛋白的降解程度有关。     

Chronic stress and its effects on adrenal cortex apoptosis in pregnant rats

The model of chronic intermittent stress by immobilization during pregnancy may produce alterations in the mechanisms that maintain adrenal gland homeostasis. In earlier investigations using this model, significant variations in plasma prolactin and corticosterone levels, and adrenal gland weights were observed. We hypothesized that chronic stress causes changes in apoptosis in the adrenal glands of pregnant rats. We identified and quantified apoptotic cells in the adrenal cortex and examined their ultrastructural characteristics using transmission electron microscopy. Adrenal glands of pregnant rats at gestation days 12, 17 and 21 were studied for control and experimental (stressed) rats. Immunolabelling techniques, stereological analysis and image quantification of adrenal gland sections were combined to determine differences in apoptosis in the different cell populations of the adrenal cortex. The apoptotic index of the experimental rats showed a significant reduction at gestation day 17, while at days 12 and 21 there were no differences from controls. Moreover, the apoptotic index of the reticular zones in control and experimental animals showed a significant increase compared to the glomerular and fascicular zones at the three gestation times studied. Chronic stress by immobilization reduced the caspase-dependent apoptotic index at gestation day 17, which may be related to variations in plasma concentrations of estrogens and prolactin.     

氨基羟乙酸对慢性酒精中毒大鼠学习记忆的影响及可能的机制

目的：探究氨基羟乙酸（AOAA）对慢性酒精中毒大鼠学习记忆能力及可能机制的影响。方法：将60只SD雄性大鼠随机均分为3组（n=20）：空白对照组、模型组和治疗组。模型组和治疗组饮含6%（v/v）酒精水溶液28 d。14 d后,治疗组连续14 d腹腔注射AOAA（5 mg/kg·d）注射液,其余两组注射等量生理盐水。实验结束前5 d连续进行5 d的水迷宫实验,实验结束取大鼠海马组织检测H₂S含量、线粒体ATP酶活性及5-HT受体蛋白的表达。结果：与空白对照组比较,模型组大鼠水迷宫实验的第2~4日潜伏期、第2~4日游泳距离、H₂S含量均升高,ATP酶活性和海马CA1、CA3区5-HT受体阳性表达明显下降（P<0.01）;与模型组比较,治疗组大鼠第2~4日潜伏期、第2~4日游泳距离、H₂S含量均下降,ATP酶活性和海马CA1、CA3区5-HT受体阳性表达显著升高（P< 0.01）。结论：AOAA能够减轻慢性酒精中毒大鼠的症状,可能与AOAA影响H₂S的含量、线粒体酶活性、5-HT受体的含量有关。     

Changes in masculine sexual behavior, corticosterone and testosterone in response to acute and chronic stress in male rats

Chronic exposure to stressors increases HPA axis activity and concomitantly reduces HPG axis activity. This antagonistic relationship between both these axes has been proposed to underlie the inhibition of reproductive function due to stress. Sexual behavior in males may be the most vulnerable aspect of male reproduction to acute and chronic stress and it has been suggested that alterations in sexual behavior during stress are due to the antagonistic relationship between testosterone and corticosteroids. However, only in a few studies has a correlation between the levels of testosterone and corticosterone, and sexual behavior been made. In this study, we evaluated the effects of different stressors, applied both acute and chronically, on masculine sexual behavior and whether or not these effects on sexual behavior are accompanied by changes in plasma levels of corticosterone and testosterone. Additionally, we evaluated the effect of testosterone treatment on the effects of stress on sexual behavior. Sexually experienced male rats were exposed to one of the following stressors: immobilization (IMB), electric foot shocks (EFS) or immersion in cold water (ICW). Sexual behavior and plasma levels of testosterone and corticosterone were assessed on days 1, 5, 10, 15, and 20 of stress. In a second experiment, males were castrated, treated with 3 different doses of testosterone propionate (TP) and exposed to ICW for 20 consecutive days. Sexual behavior was assessed on days 1, 5, 10, 15, and 20 and steroids were evaluated on day 20. Parameters of masculine sexual behavior were modified depending on the characteristics of each stressor. Mount, intromission and ejaculation latencies increased significantly, the number of mounts increased, and ejaculations decreased significantly in males exposed to EFS and to ICW but not in males exposed to IMB. Associated with these effects, testosterone decreased in the EFS and ICW groups on days 1, 15, and 20. However, corticosterone increased only in males exposed to ICW. In castrated males, TP treatment failed to block the effects of stress by ICW on sexual behavior and corticosterone. These results indicate that the effects of stress on sexual behavior depend on the characteristics of each stressor, and these effects, as well as the decrease in testosterone are not necessarily associated with the increase in corticosterone. The fact that testosterone treatment did not prevent the effects of stress on sexual behavior suggests that other mediators could be involved in the alterations of sexual behavior caused by stress.     

间歇运动对心梗大鼠心肌氧化应激和炎症的影响及其机制

目的:探讨间歇运动激活心肌梗死(MI)大鼠SIRT1-Nox4-ROS通路抑制心脏氧化应激和炎症的作用.方法:选取雄性SD大鼠30只,随机分为假手术对照(C)组,心肌梗死(MI)组和心梗+间歇运动(ME)组,每组10只.MI组采用心脏左冠状动脉前降支(LAD)结扎法,建立MI模型.C组大鼠实施假手术,ME组大鼠在MI手...