花椒多酚类化合物对慢性应激抑郁大鼠的治疗作用机制研究

目的探讨花椒多酚类化合物(ZPPC)对慢性应激抑郁大鼠的治疗作用及可能机制。方法将40只慢性应激模型大鼠随机均分为应激模型组,低、中、高剂量ZPPC(50,100,200 mg/kg)组和丙咪嗪(10 mg/kg)组,另设正常对照组(n=8),测定各组大鼠的开野和强迫游泳行为,酶联免疫吸附试验双抗体夹心法测定大鼠血清皮质酮质量浓度和白细胞介素1β(IL-1β)水平,并测定各组大鼠肾上腺皮质厚度。结果与应激模型组比较,低、中、高剂量的ZPPC能明显增加应激大鼠在开野箱中的活动性和探究次数,剂量依赖性地减少其在强迫游泳中的行为绝望时间,并且还能降低血清皮质酮质量浓度和IL-1β水平(均P<0.05,P<0.01,P<0.001),同时降低肾上腺皮质厚度(均P<0.01)。结论 ZPPC可以改善慢性应激引起的抑郁样行为,作用机制可能与其增强免疫功能、保护肾上腺结构和功能有关。     

山奈酚对乳腺癌抑郁模型大鼠的抗抑郁作用研究

目的 探讨山奈酚对实验性乳腺癌抑郁大鼠的抗抑郁作用。方法 90只大鼠随机分为对照组、乳腺癌组、抑郁组、复合模型组、氟西汀组、山奈酚组,每组15只。通过慢性不可预知性轻度应激方法建立大鼠抑郁模型,以二甲基苯蒽为诱导剂建立乳腺癌大鼠模型。采用旷场实验垂直运动次数及水平活动总路程观察各组大鼠自主活动;液质联检分析各组大鼠脑内海马及前额叶皮质单胺类神经递质,包括去甲肾上腺素(norepinephrine,NE)、多巴胺(dopamine,DA)和5-羟色胺(5-hydroxytryptamine,5-HT)含量的变化。结果 乳腺癌组自主活动均减少,但与对照组比较无显著性差异;抑郁组和复合模型组自主活动减少,与对照组比较差异均有显著性(P<0.01);与复合模型组相比,山奈酚组与氟西汀组垂直运动次数及水平活动总路程均显著增加(P<0.05或P<0.01)。与复合模型组比较,氟西汀组海马区DA、5-HT含量显著增高(P<0.01),前额叶皮质DA、NE、5-HT浓度均显著性增高(P<0.05);山奈酚组与复合模型组比较,海马部位NE含量明显增高(P<0.05),前额叶皮质部位DA、NE、5-HT浓度均显著性增高(P <0.05或P <0.01)。结论 山奈酚具有显著抗大鼠抑郁作用,可能通过提高前额叶皮质部位NE、DA、5-HT递质水平达到抗抑郁作用。     

漆黄素与胡椒碱联合应用的抗抑郁作用及机制研究

目的 研究低剂量漆黄素与阈下剂量胡椒碱急性给药的抗抑郁作用,初步探讨抗抑郁的作用机制。方法 采用经典的行为绝望抑郁模型,即小鼠强迫游泳实验和悬尾游泳实验,观察低剂量漆黄素与阈下剂量胡椒碱急性给药对小鼠绝望模型不动时间的影响,同时观察两药联用对小鼠自主活动的影响。应用神经化学检测方法,观察漆黄素与阈下剂量胡椒碱急性给药对单胺氧化酶活性的影响。结果 漆黄素(1.25mg·kg-1,2.5mg·kg-1,5mg·kg-1,口服(P.O)与阈下剂量胡椒碱(2.5mg·kg-1,腹腔注射(i.p.))联合应用能显著减少小鼠强迫游泳和悬尾实验中的不动时间,且实验剂量范围内药物不影响小鼠的自主活动。进一步深入研究发现造成这种结果的原因是低剂量漆黄素与阈下剂量胡椒碱合用能剂量依赖性地抑制脑内MAO-A的活性。结论 低剂量漆黄素与阈下剂量胡椒碱联合用药具有抗抑郁作用,其机制可能与抑制脑内单胺氧化酶活性,进而增加脑内胺类神经递质有关。     

咖啡酸对慢性应激大鼠的抗抑郁作用

目的探讨咖啡酸对慢性应激大鼠的抗抑郁作用。方法采用各种慢性不可预见轻微刺激建立大鼠抑郁模型。21 d后,ig给予大鼠咖啡酸10,30和50 mg.kg-1,连续21 d。通过旷场实验检测中央格停留时间、水平活动和垂直活动情况,通过强迫游泳实验检测大鼠静止不动行为百分比(PI);检测海马超氧化物歧化酶(SOD)活性与丙二醛(MDA)含量。结果与正常对照组相比,模型组大鼠在旷场实验中央格停留时间增长,水平活动和垂直活动减少,强迫游泳静止不动状态增加,SOD活性显著降低,MDA含量显著升高(P<0.01)。与模型组相比,咖啡酸10～50 mg.kg-1组能够显著缩短停留时间(P<0.05)、增加垂直活动(P<0.01),但对水平活动无明显影响。模型组PI为(79.69±15.84)%,咖啡酸10～50 mg.kg-1组PI显著降低,分别为(16.00±2.11)%,(10.33±2.92)%和(7.33±2.63)%。与正常对照组相比,模型组SOD酶活性显著降低,MDA含量显著增加(P<0.01),与模型组相比,咖啡酸10～50 mg.kg-1能够显著增加SOD酶活性,分别为模型组的1.50,2.46和2.59倍(r=0.915,P<0.01);MDA含量显著降低,分别为模型组的18.64%,11.37%和6.35%(P<0.01),且呈剂量依赖性(r=0.982,P<0.01)。咖啡酸与舍曲林5 mg.kg-1的作用相似。结论咖啡酸对慢性应激大鼠有一定的抗抑郁作用。     

解郁汤对慢性应激抑郁模型小鼠的抗抑郁作用及机制研究

目的：探讨解郁汤的抗抑郁作用及可能机制。方法：以慢性轻度不可预见性应激方法建立小鼠抑郁症模型,以糖水消耗、悬尾实验、强迫游泳实验、开野实验进行行为学评分,并通过UPLC—T—QMS系统检测其脑内单胺类神经递质的含量,观察模型小鼠给药前后的变化。通过免疫组化检测小鼠海马区BDNF以及5-Brdu表达。结果：与空白组相比．模型组的小鼠蔗糖水消耗量明显下降,强迫游泳不动时间、悬尾不动时间均显著增加,交叉次数、直立次数显著减少,脑内的去甲肾上腺素、5-羟色胺、5-羟色胺吲哚乙酸含量降低（P〈0．05）。与模型组相比,解郁汤组小鼠蔗糖水消耗量显著升高,强迫游泳不动时间、悬尾不动时间均显著减少（P〈0．05）。解郁汤能显著增加大鼠脑内去甲肾上腺素、5-羟色胺、5-羟色胺吲哚乙酸含量（P〈0．05）。解郁汤能增加小鼠脑内海马区BDNF以及5-Brdu表达。结论：解郁汤具有抗抑郁作用,其作用机制可能与调节中枢单胺类神经递质的调节以及促进海马神经元再生有关。     

原花青素对慢性不可预知性应激小鼠脑内单胺递质的影响

目的 研究原花青素在慢性不可预知性应激（unpredictable chronic mild stress,UCMS）小鼠中的抗抑郁样作用以及对小鼠脑内单胺递质含量的影响。方法 随机将ICR小鼠分为6组：空白对照组,UCMS组,原花青素低、中、高剂量组（UCMS+原花青素12.5,25,50 mg·kg^-1）,氟西汀组（UCMS+氟西汀10 mg·kg^-1）。采用UCMS建立模型组评估小鼠的抑郁和焦虑样行为,采用HPLC测定小鼠海马、额叶皮层和下丘脑中单胺递质的含量。结果 与空白对照组比较,UCMS组小鼠悬尾的不动时间明显增加（P<0.05）,大理石掩埋数目显著增加（P<0.01）;小鼠海马、额叶皮层和下丘脑中的去甲肾上腺素、5-羟色胺和多巴胺的含量均减少;与UCMS组比较,原花青素组能明显逆转上述行为学以及脑内单胺递质含量的改变。结论 UCMS小鼠存在抑郁焦虑样行为学的改变,海马、额叶皮层和下丘脑中单胺递质含量表达异常。原花青素可以改善UCMS小鼠行为学的改变,并调节海马、额叶皮层和下丘脑中单胺递质的表达。     

苦参碱对腺嘌呤诱导大鼠慢性肾小管-间质纤维化的作用

目的为探讨苦参碱对腺嘌呤诱导大鼠肾小管-间质纤维化的防治作用及其机制。方法60只雄性Wistar大鼠被随机分为3组①正常对照组(NCG)8只;②腺嘌呤处理组(ATG)28只;③苦参碱治疗组(MTG)24只。按250mg·kg-·1d-1体重给ATG和MTG的大鼠灌服腺嘌呤,连续21天,而灌服腺嘌呤1周后,MTG的大鼠每天还按20mg·kg-·1d-1的剂量用苦参碱腹腔注射,分别观察苦参碱治疗的大鼠在14天、21天和28天的血清尿素氮、肌酐、IL-6和肾组织病理改变等指标的变化,用放射免疫法检测血清IL-6的水平,免疫组化法检测肾组织TGF-β1蛋白的表达,并对免疫组化染色阳性信号进行半定量分析,用HE染色对各组肾小管-间质损伤进行半定量分析。结果在相同时间点上,MTG大鼠的血清肌酐、尿素氮与ATG大鼠比较,有明显的改善(P<0.05);MTG大鼠的血清IL-6水平、肾小管间质的TGF-β1蛋白表达显著低于ATG大鼠(P<0.05),但均高于NCG大鼠(P<0.01),MTG的大鼠肾小管间质损伤指数低于ATG大鼠(P<0.05)。结论在腺嘌呤诱导的大鼠肾间质纤维化过程中,苦参碱能降低其血清BUN、Scr、IL-6水平和TGF-β1蛋白在肾小管间质中的表达,阻抑肾间质纤维化的进展。     

单胺递质对皮质酮所致的PC12细胞损伤的保护作用

目的　观察单胺递质在抗抑郁剂产生的效应中所起的作用。方法　单胺递质 (5 HT、DA、NE)、去甲丙咪嗪(DIM)及MK80 1与皮质酮 0 2mmol·L-1共孵PC12细胞48h ,并用MTT比色法判断细胞损伤程度。采用Fura 2 /AM荧光标记法测定胞内Ca2 + 浓度。结果　高浓度皮质酮处理PC12细胞后 ,细胞存活率比正常组降低 ,胞内 [Ca2 + ]i升高 ,表明细胞受到损伤或部分死亡。当给予 5 HT ,DA ,NE ,DIM及MK80 1后 ,细胞存活率增高 ,而胞内 [Ca2 + ]i降低 ,细胞损伤减少或已接近正常。结论　与抗抑郁剂一样 ,单胺递质对皮质酮损伤的PC12细胞有明显的保护作用 ,并且能够明显降低皮质酮诱发的PC12细胞胞内Ca2 + 超载。提示单胺递质可能参与或介导了抗抑郁剂的神经元保护作用 ,这可能是抗抑郁剂的作用机制之一     

反式虾青素对慢性应激小鼠的抗抑郁作用及其炎症相关机制

目的 探讨反式虾青素对慢性应激小鼠的抗抑郁作用及其炎症相关机制.方法 50只雄性ICR小鼠,随机分为对照组、模型组和反式虾青素20、40和80 mg/kg给药组,每组10只.建立小鼠慢性应激模型,应激过程共计21 d,每天1次.造模期间给药组口服相应剂量的反式虾青素,对照组和模型组给予0.5％羧甲基纤维素钠,连续给药2...     

四逆散有效组分拮抗空瓶刺激所致大鼠慢性情绪应激的作用

目的:探讨四逆散有效组分拮抗慢性情绪应激大鼠的作用。方法:利用连续21 d空瓶刺激所致大鼠慢性情绪应激模型,观察四逆散有效组分(450 mg/kg/day,连续21 d)对模型大鼠的体重、行为学、血清皮质酮含量及大鼠海马组织病变的影响。结果:四逆散有效组分能够有效拮抗空瓶刺激诱导的大鼠慢性情绪应激反应,表现为大鼠体重明显升高、攻击和探究行为减少、修饰行为增加、皮质酮含量降低、改善情绪应激导致的海马损伤。结论:四逆散有效组分可能是通过抑制皮质酮的含量升高,减少海马损伤而发挥其拮抗慢性情绪应激的作用。     

Effects of montelukast, a cysteinyl-leukotriene type 1 receptor antagonist, on the pathogenesis of bleomycin-induced pulmonary fibrosis in mice

Cysteinyl-leukotrienes are potent mediators involved in various inflammatory diseases and lung disorders such as asthma. However, their precise role in the pathogenesis of pulmonary fibrosis is unknown. In the present study, we investigated the effect of montelukast, a cysteinyl-leukotriene type 1 receptor antagonist, on bleomycin-induced pulmonary fibrosis in mice. Montelukast (10 mg/kg/day) was orally administered to the bleomycin-induced pulmonary fibrosis mice for 3 days before and 14 days after intratracheal instillation of bleomycin. We evaluated the effects of montelukast on the development of pulmonary fibrosis in these mice and investigated the expression of various cytokines and two cysteinyl-leukotriene receptors. Treatment with montelukast significantly attenuated the increased fibrotic area and hydroxyproline content in the fibrotic lungs of bleomycin-instilled mice. Montelukast treatment also decreased mRNA levels of IL-6, IL-10, IL-13, and TGF-β1, all of which were elevated in fibrotic lungs. In fibrotic lungs, TNF-α and IL-1β mRNA levels were increased and IFN-γ mRNA levels were decreased, but montelukast did not affect these mRNA levels. Furthermore, cysteinyl-leukotriene type 1 receptor mRNA levels were increased, whereas cysteinyl-leukotriene type 2 receptor mRNA levels were decreased in fibrotic lungs. Montelukast treatment induced the recovery of cysteinyl-leukotriene type 2 receptor mRNA levels to normal control levels but did not change cysteinyl-leukotriene type 1 receptor mRNA levels. These results suggest that montelukast exhibits its beneficial effects by inhibiting the overexpression of IL-6, IL-10, IL-13, and TGF-β1 and by modulating the homeostatic balance between the cysteinyl-leukotriene type 1 and type 2 receptors.     

多西环素对单侧输尿管结扎大鼠肾组织的影响及可能机制

目的：探讨多西环素对肾间质纤维化的影响及可能机制。方法采用单侧输尿管结扎术（ UUO ）致肾小管间质纤维化大鼠模型。将72只SD大鼠随机分为假手术组、模型组、多西环素治疗组[8 mg/（ kg·d ）]。手术后7,14,21 d时分别处死各组中6只大鼠,用免疫组化方法观察大鼠肾组织中转化生长因子-β1（ TGF-β1）、基质金属蛋白酶2（ MMP-2）表达情况。行HE及Masson染色评定大鼠肾脏的病理情况。结果模型组各时间点MMP-2表达明显低于同期假手术组（ P〈0.05）,多西环素组各时间点MMP-2表达明显低于同期模型组（ P〈0.05）,多西环素组术后14 d及术后21 d低于术后7 d。模型组各时间点TGF-β1表达明显高于同期假手术组（ P〈0.05）,而多西环素组术后7 d TGF-β1表达明显低于同期模型组,多西环素组术后14 d及术后21 d高于术后7 d。结论多西环素在肾小管间质纤维化的早期对肾脏有保护作用。     

The Effect of Antidepressant Medication Treatment on Serum Levels of Inflammatory Cytokines: A Meta-Analysis

Serum levels of inflammatory cytokines, for example, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1 beta (IL-1β), are elevated in subjects with major depressive disorder (MDD). The reason why this occurs is unclear. Elevated levels of inflammatory cytokines could be a result of brain dysfunction in MDD. It is also possible that inflammatory cytokines contribute to depressive symptoms in MDD. If the first assumption is correct, one would expect levels to normalize with resolution of the depressive episode after treatment. Several studies have measured changes in cytokine levels during antidepressant treatment; however, the results vary. The purpose of this study was to pool all available data on changes in serum levels of TNFα, IL-6, and IL-1β during antidepressant treatment to determine whether these levels change. Studies were included if they used an approved pharmacological treatment for depression, patients had a diagnosis of MDD, and serum levels of TNFα, IL-6, and/or IL-1β were measured before and after treatment. Twenty-two studies fulfilled these criteria. Meta-analysis of these studies showed that, overall, while pharmacological antidepressant treatment reduced depressive symptoms, it did not reduce serum levels of TNFα. On the other hand, antidepressant treatment did reduce levels of IL-1β and possibly those of IL-6. Stratified subgroup analysis by class of antidepressant indicated that serotonin reuptake inhibitors may reduce levels of IL-6 and TNFα. Other antidepressants, while efficacious for depressive symptoms, did not appear to reduce cytokine levels. These results argue against the notion that resolution of a depressive episode is associated with normalization of levels of circulating inflammatory cytokines; however, the results are consistent with the possibility that inflammatory cytokines contribute to depressive symptoms and that antidepressants block the effects of inflammatory cytokines on the brain.     

苡仁六妙颗粒对混合菌液所致大鼠慢性盆腔炎的治疗作用

目的:研究苡仁六妙颗粒对大鼠慢性盆腔炎的作用.方法:采用混合菌液造模法制备慢性盆腔炎大鼠模型,测定大鼠血清白介素-2(IL-2)、白介素-6(IL-6)的浓度变化及胸腺指数.结果:治疗组大鼠血清IL-2、IL-6、胸腺指数值与模型组相比有显著性差异(P＜0.05),其中治疗高剂量组与模型组相比有极显著性差异(P＜0.0...     

云南红药对类风湿性关节炎模型大鼠足肿胀的抑制作用及对大鼠血清中致炎因子水平的影响

目的：研究云南红药对类风湿性关节炎模型大鼠足肿胀的抑制作用以及对大鼠血清IL-1β和TNF-α含量的影响,并探讨其作用机制。方法：将60只SD大鼠随机分成空白组、模型组、阳性对照组以及云南红药高、中、低剂量组。除空白组外,用Ⅱ型胶原蛋白诱导其余各组大鼠建立类风湿性关节炎模型。阳性对照组灌胃给予地塞米松磷酸钠2 mg.kg-1,云南红药高、中、低剂量组分别灌胃给予云南红药0.4、0.2和0.1 g.kg-1,空白组、模型组灌胃给予生理盐水0.01 mL.g-1,所有大鼠均为每日给药1次,连续28天。记录各组大鼠右后足肿胀程度变化情况,并于第28天处死大鼠,检测其血清IL-1β和TNF-α的含量。结果：模型组大鼠在注射Ⅱ型胶原蛋白后的第15天,云南红药高、中、低3个剂量组的大鼠分别在注射Ⅱ型胶原蛋白后的第22、20、18天右足肿胀率达100%;与模型组相比,云南红药高、中剂量在给药16天后即能显著抑制大鼠足肿胀（P〈0.05）,而云南红药低剂量组在给药24天后才产生显著抑制作用（P〈0.05）;云南红药高、中剂量组大鼠的血清IL-1β和TNF-α的含量明显低于模型组（P〈0.01）,模型组大鼠血清中IL-1β和TNF-α的含量分别为152.34 ng.L-1和31.76μg.L-1,高剂量组分别为69.64 ng.L-1和15.37μg.L-1,中剂量组分别为82.21 ng.L-1和19.44μg.L-1。结论：云南红药能够有效阻止类风湿性关节炎的发生、发展,其作用机制可能与下调致炎因子IL-1β和TNF-α的水平有关。     

糖代谢异常对急性心肌梗死患者血清炎性细胞因子TNF-α和IL-6的影响

目的 了解糖代谢异常对急性心肌梗死患者血清炎性细胞因子TNF-α和IL-6的影响.方法 急性心肌梗死患者根据OGTF检测结果将其分为糖耐量正常(NGT)、糖耐量异常(IGT)和糖尿病(DM)三组.应用ELISA方法测定三组患者血清TNF-α和IL-6的含量.结果 AMI合并DM患者血清TNF-α和IL-6的浓度高于NGT和IGT患者,P<0.05.心功能killip3～4级患者血清TNF-α和IL-6的浓度也高于killip1～2级患者,P<0.05.结论 糖尿病加剧了急性心肌梗死时的炎症反应.     

Possible Mechanisms Underlying Statin-Induced Skeletal Muscle Toxicity in L6 Fibroblasts and in Rats

3-Hydroxy-3-methylglutaryl CoA reductase inhibitors (statins) are safe and well-tolerated therapeutic drugs. However, they occasionally induce myotoxicity such as myopathy and rhabdomyolysis. Here, we investigated the mechanism of statin-induced myotoxicity in L6 fibroblasts and in rats in vivo. L6 fibroblasts were differentiated and then treated with pravastatin, simvastatin, or fluvastatin for 72 h. Hydrophobic simvastatin and fluvastatin decreased cell viability in a dose-dependent manner via apoptosis characterized by typical nuclear fragmentation and condensation and caspase-3 activation. Both hydrophobic statins transferred RhoA localization from the cell membrane to the cytosol. These changes induced by both hydrophobic statins were completely abolished by the co-application of geranylgeranylpyrophosphate (GGPP). Y27632, a Rho-kinase inhibitor, mimicked the hydrophobic statin-induced apoptosis. Hydrophilic pravastatin did not affect the viability of the cells. Fluvastatin was continuously infused (2.08 mg/kg at an infusion rate of 0.5 mL/h) into the right internal jugular vein of the rats in vivo for 72 h. Fluvastatin infusion significantly elevated the plasma CPK level and transferred RhoA localization in the skeletal muscle from the cell membrane to the cytosol. In conclusion, RhoA dysfunction due to loss of lipid modification with GGPP is involved in the mechanisms of statin-induced skeletal muscle toxicity.     

结肠清颗粒对溃疡性结肠炎模型大鼠血清IL-1、ICAM-1含量的影响

目的：探讨结肠清颗粒对溃疡性结肠炎模型大鼠血清白细胞介素1（IL-1）、细胞黏附因子（ICAM-1）的影响。方法：用家兔结肠加弗氏佐剂复制大鼠溃疡性结肠炎模型,检测模型大鼠血清IL-1、ICAM—1含量。结果：结肠清颗粒能显著增加溃疡性结肠炎模型大鼠血清IL-1及ICAM-1的含量;显著降低溃疡性结肠炎模型大鼠结肠的病理改变,对模型大鼠结肠有显著的修复作用。结论：结肠清颗粒治疗溃疡性结肠炎的作用可能与其升高血清IL-1及ICAM-1的含量,从而改善免疫功能。减轻炎症损伤有关。