针刺对快速老化小鼠海马神经干细胞增殖、分化的影响

目的研究针刺疗法对快速老化小鼠（SAMP8）海马神经干细胞（NSCs）增殖、分化的影响。 方法将24只SAMP8小鼠随机分为模型组与针刺组,12只抗快速老化模型小鼠（SAMR1）作为正常对照组(正常组),针刺组选百会穴进行针刺治疗,每天治疗1次,7 d为1个疗程,共治疗3个疗程。处死前1周开始给予小鼠腹腔注射5-溴-2′-脱氧尿苷（BrdU）,50 mg/kg体重,每日1次。动物处死后取海马组织,用免疫荧光双标方法检测NSCs的增殖、分化。 结果各组小鼠海马区都存在BrdU/nestin阳性细胞表达,与正常组比较,模型组小鼠阳性细胞数减少,差异有统计学意义（P<0.01）;与模型组比较,针刺组小鼠阳性细胞数增多,差异有统计学意义（P<0.05）。各组小鼠海马区都存在NSCs分化的新生神经细胞阳性表达,与模型组比较,针刺组NSCs向成熟神经元及未成熟神经元的分化不明显（P&rt;0.05）。针刺能使SAMP8增多的成熟星形胶质细胞表达下降,减少的未成熟星形胶质细胞表达增多,但针刺组与模型组比较,差异均无统计学意义（P&rt;0.05）。与正常组比较,模型组少突胶质细胞明显增多（P<0.05）;针刺能抑制少突胶质细胞的表达,针刺组与模型组比较差异有统计学意义（P<0.05）。 结论针刺治疗能促进SAMP8海马NSCs增殖,抑制其向少突胶质细胞分化,但对向神经元、未成熟星形胶质细胞分化的影响不明显。     

远志皂苷元对新生大鼠海马神经干细胞分化的影响

目的观察远志皂苷元对体外培养的胎鼠海马神经干细胞(NSCs)增殖分化的影响。方法利用无血清DMEM/F12 体外培养技术从新生Wistar 大鼠大脑海马中培养NSCs,添加不同浓度(0、1、2、4 μg/ml)远志皂苷元。应用免疫荧光技术对NSCs及其分化后的细胞进行鉴定。结果培养的NSCs能够表达Nestin,并具有分化为神经元、星形胶质细胞及少突胶质细胞的能力。在同一接种密度条件下,远志皂苷元干预组的Nestin 阳性细胞数较对照组减少(P<0.05),神经元特异性烯醇化酶(NSE)和胶质纤维酸性蛋白(GFAP)阳性细胞数较对照组增加(P<0.05)。结论远志皂苷元能促进新生大鼠大脑海马NSCs的分化。     

脑康Ⅱ号对新生大鼠海马神经干细胞增殖分化的影响

目的 探讨脑康Ⅱ号含药血清对体外培养大鼠海马神经干细胞(NSCs)增殖分化作用的影响.方法 用无血清DMEM/F12[含20 μg/L碱性成纤维细胞生长因子(bFGF)和表皮生长因子(EGF)及B27]体外培养新生Wistar大鼠海马NSCs,在NSCs分化过程中添加大、中、小剂量(分别为2.0、1.0、0.5 kg/L)脑康Ⅱ号含药血清进行干预,以免疫荧光及细胞化学方法对NSCs及其分化后的细胞进行鉴定.结果 从新生大鼠海马分离培养的NSCs能够表达巢蛋白,并具有分化为神经元和星形胶质细胞的能力;5 d时,脑康Ⅱ号各剂量组神经球突起长度均显著长于对照组(P<0.05或P<0.01);与对照组比较,脑康Ⅱ号各剂量组细胞分化为神经元或星形胶质细胞率均明显升高(P<0.05或P<0.01).结论 脑康Ⅱ号可促进NSCs向神经元方向分化,并对所分化的神经元样细胞有促生长、发育作用.     

人颞叶内侧癫痫海马组织星形胶质细胞Syntrophin的表达变化

目的观察人颞叶内侧癫痫(MTLE)海马组织星形胶质细胞syntrophin的表达变化。方法 2015年4月至2016年7月,17例癫痫患者手术切除的海马组织,依据苏木素-伊红(HE)染色及胶质原纤维酸性蛋白、神经元核抗原免疫组织化学染色结果,分为MTLE组13例和非MTLE组4例。免疫荧光双重组织化学法及免疫荧光组织化学法观察syntrophin的表达。结果 MTLE组星形胶质细胞大量增生,神经元明显减少。syntrophin在星形胶质细胞膜及足突处表达。与非MTLE组相比,MTLE组syntrophin在血管周围星形胶质细胞足突处分布减少,在其他部位分布增加。图像分析显示,与非MTLE组相比,MTLE组syntrophin蛋白量显著增多(t=5.421,P0.001)。结论海马组织syntrophin在星形胶质细胞上的分布及其整体表达变化可能与MTLE发生相关。     

电针百会、大椎、肾俞穴对SAMP8小鼠学习记忆与海马CA1区神经元突触的影响

目的观察电针百会、大椎、肾俞穴对SAMP8小鼠学习记忆与海马CA1区神经元突触的影响,探讨电针治疗阿尔茨海默病(AD)的机制。方法 7月龄SAMP8小鼠24只随机分为模型组和电针组,同龄正常老化SAMR1小鼠12只为对照组。电针组电针百会、大椎、肾俞穴30 d。Morris水迷宫检测小鼠学习记忆能力,免疫组织化学观察小鼠海马CA1区突触素(SYN)及突触后致密区蛋白95(PSD95)的表达,透射电镜观察小鼠海马CA1区突触超微结构的变化。结果与模型组相比,电针组逃避潜伏期缩短(P0.05),原平台象限停留时间延长(P0.05),穿越原平台次数增加(P0.05),海马CA1区SYN与PSD95表达显著提高(P0.001),突触结构较完整,数量增加。结论电针能提高小鼠海马CA1区神经元突触蛋白的表达,改善突触的超微结构,从而有效改善SAMP8小鼠的学习记忆能力。     

pEGFP/A_2M(FP_6)转染神经干细胞海马移植治疗APP/PS1双转基因AD小鼠的实验观察

目的:携带pEGFP/A2M(FP6)的神经干细胞(NSCs)定向移植到APP/PS1双转基因AD小鼠海马内,观察移植细胞的分化、迁移,脑内Aβ沉积的变化,以及对AD小鼠学习记忆功能的影响。方法:APP/PS1转基因AD小鼠分为假手术(SO)组、人工脑脊液(ACSF)组、转染pEGFP的NSCs(pEGFP-NSCs)组及转染pEGFP/A2M(FP6)的NSCs(pEGFP/A2M(FP6)-NSCs)组,移植物小鼠海马CA1区定位注射,水迷宫实验检测小鼠认知功能,免疫组化观察小鼠脑内移植细胞的分化、迁移及Aβ病理变化。结果:pEGFP/A2M(FP6)-NSCs组和pEGFP-NSCs组转基因小鼠逃避潜伏期较SO组及ACSF组显著缩短(P<0.05);pEGFP/A2M(FP6)-NSCs组转基因小鼠逃避潜伏期较pEGFP-NSCs组缩短(P<0.05)。pEGFP/A2M(FP6)-NSCs组和pEGFP-NSCs组转基因小鼠海马及皮质内,部分Aβ染色阳性斑块周围可见表达EGFP的移植细胞。pEGFP/A2M(FP6)-NSCs组转基因小鼠额叶、海马区域,Aβ染色阳性斑块数量和平均面积均较其他3组显著减少(P<0.05)。移植的NSCs,部分细胞Nestin染色呈阳性,部分细胞GFAP染色呈阳性,少数细胞MAP-2染色呈阳性。结论:移植pEGFP/A2M(FP6)NSCs到APP/PS1双转基因AD小鼠海马,可减少AD小鼠脑内Aβ斑块沉积,部分移植的NSCs分化为神经元及星形胶质细胞,小鼠的学习记忆功能显著改善。     

姜黄素早期干预对孤独症模型鼠海马神经元和星形胶质细胞的影响

摘要 目的：研究孤独症模型鼠海马神经元和星形胶质细胞的变化以及姜黄素早期干预对二者表达的影响。 方法：根据Schneider的方法,对孕12.5天Wistar大鼠腹腔注射丙戊酸钠600mg/kg建立子代孤独症模型,正常组注射同等剂量的生理盐水（正常组）,分别对两组仔鼠进行模型鉴定。随机选取7日龄模型仔鼠20只,正常组仔鼠10只。模型组仔鼠随机分为模型组10只和姜黄素组10只。姜黄素组于7日龄连续3周腹腔注射姜黄素50mg/kg[姜黄素用含1ml/L二甲基亚砜（dimethyl sulfoxide, DMSO）的PBS液配成10g/L的溶液],正常组、模型组于7日龄连续三周腹腔注射同等剂量的含1ml/L DMSO的PBS液。利用尼氏染色、免疫荧光染色观察比较28日龄三组仔鼠海马神经元和星形胶质细胞的形态和数量。 结果：发育方面：与正常组相比,模型组体重明显降低;行为学方面：模型组社会交往和交流次数减少,重复性刻板行为增加,并且学习记忆能力下降;尼氏染色：正常组神经元排列紧密规则,面积大小无明显差别,数量较多;模型组神经元排列稀疏且不规则,面积较小,数量减少;姜黄素组神经元排列较规则,数量有所增加;免疫荧光染色：姜黄素干预后神经元数量增加（P＜0.05）,星形胶质细胞数量降低（P＜0.05）。 结论：孤独症模型仔鼠海马神经元和星形胶质细胞表达异常;姜黄素早期干预后上调了神经元的表达,抑制了星形胶质细胞的表达。     

神经干细胞联合神经生长因子纳米粒海马移植对APP/PS1转基因小鼠行为学及海马突触素的影响

目的 观察神经干细胞（NSCs）联合神经生长因子（NGF）纳米粒海马移植对APP/PS1双转基因小鼠行为学及海马突触素（SYP）的影响。 方法 体外分离培养增强型绿色荧光蛋白（EGFP）转基因小鼠胎脑来源NSCs,24只12月龄雄性APP/PS1双转基因AD小鼠随机分入NSCs联合NGF纳米粒移植组（NSCs+NGF-NP组）、NSCs移植组（NSCs组）和AD对照组（AD组）,每组8只,另选8只同月龄雄性野生型小鼠作为健康对照组（WT组）。NSCs+NGF-NP组和NSCs组分别行NSCs联合NGF纳米粒移植和NSCs移植,其余两组均行等量磷酸盐缓冲液（PBS）注射,移植部位为双侧海马区。移植4周后,采用Morris水迷宫检测4组小鼠学习记忆功能,用免疫荧光组化法检测移植细胞的迁移与分化,Western blot检测SYP蛋白水平。 结果 体外悬浮培养的神经球表达EGFP阳性,免疫荧光显示NSCs特异性标志物Nestin阳性。移植4周后,可见EGFP示踪的NSCs在海马注射移植部位存活并向胼胝体,海马深部和齿状回迁移,可分化为双皮质素（DCX）阳性神经元及胶质纤维酸性蛋白（GFAP）阳性胶质细胞,并可见NSCs+NGF-NP组存活细胞数量较多,突起较长,穿越海马颗粒层。海马突触相关蛋白SYP检测显示, WT组、NSCs组和NSCs+NGF-NP组海马SYP蛋白水平较AD组明显增高（P＜0.05）,NSCs+NGF-NP组SYP蛋白水平明显高于NSCs组（P＜0.05）,且与WT组比较,差异无统计学意义（P＞0.05）。水迷宫检测显示,与AD组比较,WT组、NSCs组和NSCs+NGF-NP组在平台象限停留时间及穿越平台次数均增加（P＜0.05）,NSCs+NGF-NP组穿越平台的次数大于NSCs组（P＜0.05）,且与WT组比较,差异无统计学意义（P＞0.05）。 结论 NSCs联合NGF纳米粒海马移植治疗可能促进移植细胞在体内存活及成熟,增加海马突触,从而改善AD小鼠学习记忆功能。     

电针百会、大椎、肾俞穴对SAMP8小鼠学习记忆与海马CA1区神经元突触的影响北大核心CSCD

目的观察电针百会、大椎、肾俞穴对SAMP8小鼠学习记忆与海马CA1区神经元突触的影响,探讨电针治疗阿尔茨海默病(AD)的机制。方法 7月龄SAMP8小鼠24只随机分为模型组和电针组,同龄正常老化SAMR1小鼠12只为对照组。电针组电针百会、大椎、肾俞穴30 d。Morris水迷宫检测小鼠学习记忆能力,免疫组织化学观察小鼠海马CA1区突触素(SYN)及突触后致密区蛋白95(PSD95)的表达,透射电镜观察小鼠海马CA1区突触超微结构的变化。结果与模型组相比,电针组逃避潜伏期缩短(P<0.05),原平台象限停留时间延长(P<0.05),穿越原平台次数增加(P<0.05),海马CA1区SYN与PSD95表达显著提高(P<0.001),突触结构较完整,数量增加。结论电针能提高小鼠海马CA1区神经元突触蛋白的表达,改善突触的超微结构,从而有效改善SAMP8小鼠的学习记忆能力。     

GFP+小鼠胚胎干细胞移植入脑出血大鼠脑内后存活与分化的研究

目的:研究小鼠胚胎干细胞(mESCs)移植入脑出血大鼠脑内后的存活与分化.方法:将小鼠胚胎干细胞用绿色荧光蛋白(GFP)标记,经G418筛选1个月使其稳定表达,制作大鼠脑出血模型(脑出血组),3 d后移植GFP 小鼠胚胎干细胞至出血灶对侧侧脑室内及健康大鼠(对照组)侧脑室内;4周后处死大鼠,免疫荧光染色后显微镜观察小鼠胚胎干细胞的生长分化情况.结果:小鼠胚胎干细胞脑内移植至大鼠侧脑室后能有效穿透脑室壁进入脑组织,向病灶方向迁徙,脑出血组移植入侧脑室的小鼠胚胎干细胞进入脑实质的数量明显多于对照组(P＜0.05),移植细胞向神经元与胶质细胞分化.结论:小鼠胚胎干细胞无论在健康大鼠或脑出血大鼠脑内都能存活,且能穿越脑室壁,进入脑实质内;同时细胞有能力向神经细胞(包括神经元与胶质细胞)分化,具有治疗脑卒中乃至脑变性疾病的巨大前景.     

Modulation of infection-induced inflammation and locomotive deficit and longevity in senescence-accelerated mice-prone (SAMP8) model by the oligomerized polyphenol Oligonol.

Oligonol is produced from the oligomerization of polyphenols (typically proanthocyanidin from a variety of fruits such as lychees, grapes, apples, persimmons, etc.) and contains catechin-type monomers and oligomers of proanthocyanidins. The ability of Oligonol to affect infection-dependent eye inflammation, locomotion and longevity in senescence-accelerated prone mice (SAMP8) (a model of senescence acceleration and geriatric disorders with increased oxidative stress and neuronal deficit) was investigated. Oligonol (60mg/kg) significantly modulated the extent of inflammation scores in the eye of SAMP8 mice. Examination of the mice indicated infection with mouse hepatitis virus and pinworm (Syphacia obvelata) in both males and females and with the intestinal protozoa (trichomonad) in males. A comparison of the two groups (using log-rank test) and the difference in the mean life span between groups (using Student's t-test) indicated significant differences in survival (p=0.043) and the mean life span (p=0.033) in male SAMP8 mice. Oligonol increased the mean life span and this was statistically significant. In the open-field locomotive test, the 7-week-old SAMP8 mice crossed more than 40 partitioned lines in 1min. At 48-week-old control untreated male SAMP8 crossed 2 lines. The Oligonol-treated 48-week-old male SAMP8 mice crossed 17 lines however. The improved locomotive activity was statistically significant even after 36weeks in the Oligonol-treated male SAMP8 but this was not the case throughout the time course of the study in the Oligonol-treated female SAMP8. Thus Oligonol treatment to SAMP8 mice modulated the severity of infection-dependent inflammation, prolonged life-span and significantly improved locomotive activity indicating potential benefit to aging-associated diseases such as Alzheimer's or Parkinson's diseases. This presents potential for further research to define infection-dependent inflammation associated with degenerative conditions and the molecular mechanism of dietary antioxidant protection.     

环境对雄性快速老化小鼠P8血促肾上腺皮质激素、皮质醇与睾酮浓度的影响

目的 不同环境对雄性快速老化小鼠P8（SAMP8）血促肾上腺皮质激素（ACTH）、皮质醇和睾酮水平的影响。 方法 将雄性SAMP8小鼠30只随机分为丰富环境组、贫瘠环境组和标准环境组，每组10只，均在对应环境中生活8周。8周后采用放射免疫方法测定血ACTH、皮质醇和睾酮水平。 结果 饲养8周后，贫瘠组、丰富组和标准组血ACTH浓度分别为（60.54±16.22）pg/ml、（48.98±15.30）pg/ml和（28.49±8.24）pg/ml；血皮质醇浓度分别为（5.37±0.81）ng/ml、（4.09±0.92）ng/ml、（3.19±0.88）ng/ml；血睾酮浓度分别为（2.35±0.90）ng/ml、（7.07±1.57）ng/ml、（3.16±1.10）ng/ml。标准环境组小鼠的血ACTH水平和血皮质醇水平与贫瘠环境组比较，差异均有统计学意义(P<0.05)，标准环境组的血ACTH水平和血睾酮水平与丰富环境组比较，差异有统计学意义(P<0.05)，丰富环境组小鼠的血皮质醇水平和血睾酮水平与贫瘠环境组比较，差异有统计学意义(P<0.05)。 结论 贫瘠环境可促进SAMP8小鼠血ACTH分泌，皮质醇增多，并激活下丘脑-垂体-肾上腺（HPA）轴。丰富环境对SAMP8小鼠血ACTH的产生和血睾酮浓度的升高有促进作用，但对皮质醇的促进作用不明显。     

Drinking Hydrogen Water Ameliorated Cognitive Impairment in Senescence-Accelerated Mice

Hydrogen has been reported to have neuron protective effects due to its antioxidant properties, but the effects of hydrogen on cognitive impairment due to senescence-related brain alterations and the underlying mechanisms have not been characterized. In this study, we investigated the efficacies of drinking hydrogen water for prevention of spatial memory decline and age-related brain alterations using senescence-accelerated prone mouse 8 (SAMP8), which exhibits early aging syndromes including declining learning ability and memory. However, treatment with hydrogen water for 30 days prevented age-related declines in cognitive ability seen in SAMP8 as assessed by a water maze test and was associated with increased brain serotonin levels and elevated serum antioxidant activity. In addition, drinking hydrogen water for 18 weeks inhibited neurodegeneration in hippocampus, while marked loss of neurons was noted in control, aged brains of mice receiving regular water. On the basis of our results, hydrogen water merits further investigation for possible therapeutic/preventative use for age-related cognitive disorders.     

Telomere length, telomerase activity and osteogenic differentiation are maintained in adipose-derived stromal cells from senile osteoporotic SAMP6 mice

Adipose tissue provides for a rich and easily accessible source of multipotent stromal cells and thus offers the potential for autologous cell-based therapy for a number of degenerative diseases. Senile osteoporosis is characterized by a reduction in bone quality, which is associated with inadequacies in bone marrow stromal cell (BMSC) differentiation. In the present study, we have characterized adipose-derived stromal cells (ASCs) isolated from aged osteoporotic mice and evaluated their suitability as a source of osteogenic precursor cells. Significant reductions in both tibia bone quality and telomere length in liver tissue were observed in the senescence-accelerated mouse prone 6 strain (SAMP6), as compared to the control age-matched senescence-accelerated mouse resistant 1 strain (SAMR1), thus confirming osteoporosis and accelerated ageing traits in this model. ASCs isolated from inguinal fat expressed mesenchymal surface markers and were capable of differentiating along the osteoblast, adipocyte and chondrocyte lineages. Telomere length was not compromised in ASCs from SAMP6 mice but was actually found to be significantly increased as compared to control SAMR1 mice. Furthermore, ASCs from both strains were comparable in terms of telomerase activity, p21 mRNA expression, SA-β-gal activity and proliferative capacity. The overall osteogenic and adipogenic potential of ASCs was comparable between SAMP6 and SAMR1 strains, as determined by quantitative molecular, biochemical and histological analyses. In conclusion, adipose tissue may represent a promising autologous cell source for the development of novel bone regenerative therapeutic strategies in the treatment of age-related osteoporosis.     

Effects of chronic cigarette smoke inhalation on the development of senile lung in senescence-accelerated mouse

The senescence-accelerated mouse (SAM) manifests most of the features of function and morphology in the senile lung with aging. However, little is known about the effects of age and cigarette smoke on alterations of the lung in SAM. In the present study, we examined the effects of chronic cigarette smoke inhalation and age on the function and morphology of lungs in two strains of SAM, SAMP2 (senescence-prone strain) and SAMR1 (senescence-resistant strain), from 6 months of age (young) and 18 months of age (aged). After 4 weeks of cigarette smoke inhalation, a small but significant airspace along with a leftward shift of the pressure-volume (P-V) curve was observed in young SAMP2, but not in SAMR1. However, the airspace size of young SAMP2 with cigarette inhalation was smaller than that in aged SAM with air inhalation, suggesting that the effect of age may be greater than that of the small burder of tobacco smoke on the lung alterations in SAMP2. In the aged SAM, there were no differences in function and structure between tobacco-exposed and air-exposed mice. Because the changes in the lungs of young SAMP2 exposed to cigarette smoke were partly simulated with age-related alterations in human lung, and because age-dependent changes of lungs were clearly investigated in SAMP2, this strain may be an interesting animal model for investigating the effects of age and/or cigarette smoke on alterations in lung structure and function.     

嗅三针对SAMP8小鼠海马磷酸化PI3K/Akt蛋白表达和突触可塑性的影响

目的:观察嗅三针对SAMP8小鼠海马磷酸化PI3K、Akt蛋白表达和海马突触可塑性损伤的影响,探讨嗅三针治疗阿尔茨海默病(AD)模型小鼠的作用机制。方法:将40只SAMP8小鼠随机分为模型组(Model)、嗅三针组(XSZ)、嗅神经切断嗅三针组(XSZ+XSJ)和盐酸多奈哌齐组(Donepezil),每组10只,10只SAMR1小鼠作为正常组(Control)。XSZ组和XSZ+XSJ组采用电针刺激印堂穴和双侧迎香穴,Donepezil组采用盐酸多奈哌齐灌胃,Control组和Model组不干预。采用Morris水迷宫实验评价小鼠学习记忆能力,新物体识别实验评价小鼠新物体识别能力,Western Blot和免疫组化检测小鼠海马区p-PI3K和p-Akt蛋白表达,透射电镜观测小鼠海马突触超微结构。结果:与Model组比较,XSZ和Donepezil干预均可以明显降低SAMP8小鼠4d平均逃避潜伏期,增加其靶象限停留时间、穿越平台次数和新物体偏爱指数,明显升高其海马p-PI3K和p-Akt蛋白表达(P<0.05),改善其海马神经元突触结构;XSZ+XSJ对于SAMP8小鼠学习记忆能力、新物体识别能力指标及p-PI3K、p-Akt蛋白表达无显著影响(P>0.05),对其突触结构损伤无明显改善;对于上述指标的影响,XSZ组与Donepezil组比较无显著差异(P>0.05)。结论:嗅三针可能基于嗅觉通路完整性,调节海马PI3K/Akt磷酸化表达,修复海马突触形态结构损伤,改善海马突触可塑性,从而发挥提高SAMP8小鼠学习记忆能力的效应。     

Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence.

Bone marrow is the principal site for osteoclastogenesis and osteoblastogenesis; and an increase in the former has been linked with bone loss caused by acute loss of gonadal steroids. We have now used an established murine model of accelerated senescence and osteopenia (SAMP6) to test the hypothesis that reduced osteoblastogenesis is linked with decreased bone mass. At 1 mo of age, the number of osteoblast progenitors in SAMP6 marrow was indistinguishable from controls; however a threefold decrease was found at 3-4 mo of age. Impaired osteoblast formation was temporally associated with decreased bone formation and decreased bone mineral density, as determined by histomorphometric analysis of tetracycline-labeled cancellous bone and dual-energy x-ray absorptiometry, respectively. Osteoclastogenesis determined in ex vivo bone marrow cultures was also decreased in these mice, as was the number of osteoclasts in histologic sections. Moreover, unlike controls, senescence-accelerated mice failed to increase osteoclast development after gonadectomy. The osteoclastogenesis defeat was secondary to impaired osteoblast formation as evidenced by the fact that osteoclastogenesis could be restored by addition of osteoblastic cells from normal mice. These findings provide the first demonstration of a link between low bone mineral density and decreased osteoblastogenesis in the bone marrow and validate the senescence-accelerated mouse as a model of involutional osteopenia.     

纳洛酮对三氯化铝致急性衰老小鼠记忆障碍的保护作用及其机制

背景老年性痴呆患者脑细胞中铝的含量普遍增高.大脑铝中毒与老年性痴呆有一定内在联系.纳洛酮是阿片受体特异性拮抗剂,国外有用于老年性痴呆治疗的报道.目的探讨纳洛酮对三氯化铝所致急性衰老小鼠记忆障碍的保护作用及其机制.设计随机对照观察.单位吉林医药学院.材料实验于2001-02/2003-02在吉林医药学院(原吉林军医学院)药理学实验室完成,选择健康成年昆明种小鼠100只,随机分为5组,每组20只,即对照组,模型组,纳洛酮0.1,0.3,0.9mg/kg组,除对照组外,每组小鼠每天皮下注射1次氯化铝70 mg/kg,连续注射7 d;纳洛酮组每只鼠除皮下注射氯化铝外,腹腔分别注射纳洛酮0.1,0.3,0.9 mg,/kg,对照组皮下注射等量的生理盐水.方法用跳台、避暗等实验方法测定小鼠学习记忆能力,同时测定小鼠肝丙二醛、脑B型单胺氧化酶的含量.主要观察指标①三氯化铝所致衰老模型跳台实验结果.②三氯化铝所致急性衰老模型避暗法实验结果.③各组丙二醛和B型单胺氧化酶的比较.结果①三氯化铝所致衰老模型跳台实验结果与模型组相比较,对照组及纳洛酮0.1,0.3,0.9 mg/kg剂量组能够明显减少三氯化铝小鼠5 min内受电击次数和受电击的动物数,24 h重复实验,纳洛酮能够明显延长小鼠第1次跳下平台潜伏期(P＜0.01),同时,纳洛酮能够降低三氯化铝小鼠3 min内错误总数和错误频率(P＜0.01).②三氯化铝所致急性衰老模型避暗法实验结果与模型组相比,对照组及纳洛酮0.1,0.3,0.9 mg/kg剂量组能够明显延长三氯化铝小鼠进入暗箱的潜伏期及小鼠5 min内受电击次数(P＜0.01).③各组丙二醛和B型单胺氧化酶的比较模型组丙二醛明显高于对照组和纳洛酮各剂量组(P＜0.01).模型组B型单胺氧化酶活性明显高于其他各组(P＜0.01).结论纳洛酮对三氯化铝所致急性衰老小鼠记忆障碍具有保护作用,能增强学习记忆能力.其作用机制可能和降低B型单胺氧化酶、清除过氧化脂质作用有关.     

NOD2 drives early IL-33–dependent expansion of group 2 innate lymphoid cells during Crohn’s disease–like ileitis

Innate lymphoid cells (ILCs) are enriched at barrier surfaces, including the gastrointestinal tract. While most studies have focused on the balance between pathogenic group 1 ILCs (ILC1s) and protective ILC3s in maintaining gut homeostasis and during chronic intestinal inflammation, such as Crohn’s disease (CD), less is known regarding ILC2s. Using an established murine model of CD-like ileitis, i.e., the SAMP1/YitFc (SAMP) mouse strain, we showed that ILC2s, compared with ILC1s and ILC3s, were increased within draining mesenteric lymph nodes and ilea of SAMP versus AKR (parental control) mice early, during the onset of disease. Gut-derived ILC2s from CD patients versus healthy controls were also increased and expanded, similarly to ILC1s, in greater proportion compared with ILC3s. Importantly, we report that the intracellular bacteria–sensing protein, nucleotide-binding oligomerization domaining–containing protein 2, encoded by Nod2, the first and strongest susceptibility gene identified for CD, promoted ILC2 expansion, which was dramatically reduced in SAMP mice lacking NOD2 and in SAMP mice raised under germ-free conditions. Furthermore, these effects occurred through a mechanism involving the IL-33/ST2 ligand-receptor pair. Collectively, our results indicate a functional link between NOD2 and ILC2s, regulated by the IL-33/ST2 axis, that mechanistically may contribute to early events leading to CD pathogenesis.     

Fish oil changes the lifespan of Caenorhabditis elegans via lipid peroxidation

Recently, we administered fish oil containing eicosapentaenoic acid and docosahexaenoic acid (DHA) to senescence-accelerated mice P8 (SAMP8), in order to investigate the effects on lifespan. Surprisingly, the lifespan of SAMP8 that were fed fish oil was shortened significantly, through a mechanism that likely involved lipid peroxidation. In this study, we investigated this phenomenon in further detail. To examine whether this phenomenon occurs only in SAMP8, we investigated the effect of fish oil on the lifespan of another organism species, Caenorhabditis elegans (C. elegans). C. elegans fed fish oil were cultured and the lifespan monitored. As a consequence of the provision of large amounts of fish oil the lifespan of C. elegans was shortened significantly, whereas an appropriate amount of fish oil extended their lifespan significantly. Lipid peroxide levels in C. elegans that were fed fish oil increased significantly in a dose-dependent manner. However, lipid peroxide levels in C. elegans were inhibited by the addition of fish oil and an antioxidant, α-tocopherol, and completely abrogated the changes in the lifespan. To further confirm whether the oxidation of n-3 polyunsaturated fatty acid in fish oil would change the lifespan of C. elegans, the effect of oxidized DHA was examined. Large amounts of oxidized DHA were found to shorten their lifespan significantly. Thus, fish oil changes the lifespan of C. elegans through lipid peroxidation.