复方地黄对阿尔次海默大鼠学习记忆及海马细胞凋亡的影响

目的观察复方地黄对阿尔海默病(Alzheimer'sdisease,AD)模型大鼠学习记忆的影响并探讨其与海马细胞凋亡的关系。方法用立体定位技术对大鼠海马CA1区微量注射喹啉酸(QA)造成AD模型,Morris水迷宫检测大鼠学习记忆水平,电子显微镜、Tunnel和流式细胞仪检测海马细胞凋亡。结果复方地黄可明显提高QA所致痴呆大鼠学习记忆水平,显著降低海马细胞的凋亡率。结论复方地黄对AD大鼠的保护作用可能与降低海马细胞凋亡有关。     

3-甲基腺嘌呤对Aβ(25-35)引起的海马神经元凋亡的影响

目的: 探讨阿尔茨海默病(AD)大鼠海马神经元自噬对凋亡的影响。方法: SD大鼠随机分成模型组、自噬抑制剂3-甲基腺嘌呤(3-MA)预处理组和对照组。模型组大鼠用立体定位技术对海马CA1区微量注射Aβ(25-35)造成AD模型;3-MA预处理组大鼠在注射Aβ(25-35)之前对海马CA1区微量注射3-MA。Morris水迷宫检测大鼠记忆水平;行为学测试后,观察海马神经元超微结构变化、自噬泡的形成、beclin-1的表达以及细胞凋亡情况。结果: 3-MA预处理组与模型组比较,大鼠学习记忆能力显著下降(P<0.05),海马神经元凋亡率显著增加(P<0.05),而beclin-1的表达量减少;模型组海马神经元可见双层膜包裹形成的自噬泡,神经元破坏程度明显轻于3-MA预处理组。结论: 抑制神经元自噬水平增加神经元凋亡;诱导神经元自噬可能是防治阿尔茨海默病的一个潜在方法。     

灵芝多糖对阿尔茨海默病大鼠海马组织形态学及抗氧化能力的影响

目的观察灵芝多糖（GLP）对阿尔茨海默病（AD）大鼠海马组织超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量以及空间学习记忆能力等的影响。方法双侧海马内一次性注射β-淀粉样多肽25～35片段（Aβ25-35）制作大鼠AD模型,腹腔注射灵芝多糖水溶液,1周后进行Morris水迷宫检测大鼠空间学习记忆能力变化。采用分光光度法测定大鼠海马组织SOD活性和MDA含量。采用透射电镜观察海马神经元的超微结构变化。以及灵芝多糖对上述各指标的影响。结果灵芝多糖能明显改善AD模型大鼠低下的空间学习记忆能力。显著提高模型大鼠海马组织SOD活性及降低MDA含量,而且灵芝多糖能明显改善模型大鼠脑组织海马CA1区神经元的退行性变化。结论灵芝多糖能提高海马内抗氧化酶SOD活性,降低丙二醛MDA含量,改善海马CA1区神经元的退行性变化。对老年性痴呆大鼠学习记忆能力可能有增强和提高作用。     

促红细胞生成素对β淀粉样蛋白诱导大鼠海马损伤的保护作用以及对大鼠学习记忆的影响

目的:探讨促红细胞生成素(erythropoietin,EPO)对阿尔茨海默病(Alzheimer disease,AD)大鼠脑损伤的保护机制。方法:采用大鼠海马内注射β淀粉样蛋白制作AD模型。将SD大鼠随机分为正常对照组、生理盐水对照组及EPO处理组。Aβ1-40大鼠海马内注射造模,在生理盐水对照组大鼠行脑室立体定向注射生理盐水,EPO处理组则行脑室立体定向注射重组人促红细胞生成素(rHu-EPO)。观察手术后7 d海马CA1区细胞凋亡变化,及缺血造模后4周大鼠学习和记忆力的变化。结果:EPO处理组大鼠海马CA1区凋亡细胞较生理盐水对照组减少(P<0.01),EPO处理组大鼠学习记忆能力明显高于生理盐水对照组(P<0.05)。结论:EPO可以抑制Aβ1-40诱导海马CA1区细胞凋亡,保护AD大鼠学习记忆功能。     

外源性硫化氢对阿尔茨海默病大鼠学习能力及海马形态学的影响

目的:观察外源性硫化氢对阿尔茨海默病大鼠的空间学习记忆功能及海马组织形态学的影响。方法:通过双侧海马内注射Aβ25-35制作大鼠AD模型,再连续7 d脑室内给予硫氢化钠。采用Morris水迷宫测试大鼠认知功能,断头取脑行HE染色、透射电镜等方法观察海马神经元的结构变化。结果:海马内注射Aβ25-35后大鼠学习记忆能力明显下降,可见海马细胞排列紊乱,核边聚、碎裂。脑室内给予硫氢化钠可显著改善大鼠认知功能,减轻海马神经元病变。结论:外源性硫化氢对Aβ25-35诱导的阿尔茨海默病模型大鼠脑组织内海马退行性变神经元有保护作用,并能改善大鼠学习记忆能力。     

β-淀粉样蛋白诱导大鼠行为学改变及星形胶质细胞变化

为了探讨不同剂量β-淀粉样蛋白 2 5 -3 5片段 ( Aβ2 5- 35)诱导老年性痴呆 ( AD)大鼠动物模型中星形胶质细胞变化与大鼠行为学改变之间的关系 ,在大鼠双侧海马内注射不同剂量 Aβ2 5- 35( 2 .5、5、10和 2 0 μg)制作大鼠 AD模型 ,注射一周后采用胶质原纤维酸性蛋白 ( GFAP)免疫组化染色、NOS组化染色及 NOS组化和 GFAP双重染色分析大鼠海马 GFAP与 NOS的表达。结果发现海马内注射 Aβ2 5- 35剂量≥ 10 μg时 ,模型组大鼠出现学习记忆减退 ,海马星形胶质细胞增生、肥大 ,数目明显多于对照组 ( P<0 .0 5 ) ;海马 NOS阳性神经元数较对照组显著减少 ( P<0 .0 5 ) ;并出现 NOS阳性星形胶质细胞。结论 :星形胶质细胞参与Aβ神经毒性导致 NOS阳性神经元损伤 ,间接导致大鼠学习记忆能力下降 ,在 AD模型大鼠早期学习记忆功能减退中起重要作用     

白花丹参根制剂对AD大鼠学习记忆和海马CA1区神经元凋亡的影响

目的:探讨白花丹参根制剂对Aβ1-40诱导的AD模型大鼠学习记忆能力及海马CA1区神经元凋亡的影响。方法:采用双侧海马微量注射凝聚状态Aβ1-40诱导AD大鼠模型。测定白花丹参根制剂干预前后AD模型大鼠学习记忆能力,海马CA1区Ach含量、Ch AT和Ach E活性,海马神经元凋亡率以及海马区Bax和Bcl-2蛋白表达的变化。结果:与正常组比较,模型组大鼠逃避潜伏期延长,穿越站台次数和第三象限游泳时间减少,大鼠海马CA1区神经内Ach含量减少,而Ch AT和Ach E活性升高,同时海马CA1区神经元凋亡率增加,Bax蛋白表达水平上调,Bcl-2蛋白表达水平下调,Bcl-2/Bax比值降低。与模型组比较,治疗组大鼠逃避潜伏期缩短,穿越站台次数明显和第三象限活动时间增加,大鼠海马CA1区神经内Ach含量升高,而Ch AT和Ach E活性降低,同时海马CA1区神经元凋亡率降低,Bax蛋白表达水平下调,Bcl-2蛋白表达水平上调,Bcl-2/Bax比值升高。结论:白花丹参根制剂可有效提高AD模型大鼠学习记忆能力,其机制可能与改善胆碱能系统的功能、上调Bcl-2和下调Bax蛋白表达水平有关。     

Aβ25-35伤害大鼠空间学习记忆和在体海马长时程增强的联合研究

目的:探讨海马内注射β-amyloid protein 25-35(Aβ25-35)所致Alzheizer’s病(AD)模型大鼠空间学习记忆功能障碍的海马突触可塑性长时程增强(LTP)机制,为联合开展AD动物行为学和在体电生理学研究提供实验证据。方法:在脑立体定位仪上给予大鼠双侧海马分别注射4 nmol/L Aβ25-35或等体积生理盐水每侧2μl,手术后恢复2周,每只大鼠依次进行行为学和电生理两部分实验。首先,利用Morris水迷宫进行空间学习、记忆功能测试;之后,进行在体海马CA1区场兴奋性突触后电位(fEPSP)引导记录实验,观察突触可塑性指标长时程增强(LTP)的改变。结果:与对照组相比,海马内注射Aβ25-35大鼠的空间学习记忆功能和在体海马突触可塑性LTP均有改变,其中:逃避潜伏期和逃避距离明显增加(P<0.01);目标象限内游泳时间和距离明显缩短(P<0.01);在体海马LTP幅度显著降低(P<0.01)。结论:海马内注射Aβ25-35可导致大鼠空间学习记忆功能障碍;联合实验中Aβ25-35同样可引起在体海马LTP改变。提示同批动物先后进行行为学和电生理学测试的方法是可行的,行为学实验不会影响后续LTP的实验结果。因此,本实验为行为学改变后进行在体LTP机制探讨提供了实验依据,为有效开展行为学和电生理学实验提供了思路。     

反式转录激活因子-X连锁凋亡抵制蛋白融合蛋白对阿尔茨海默病模型大鼠Caspase-3表达与活性的抑制

目的:探讨β-淀粉样蛋白25-35(Aβ25-35)海马内注射所致的阿尔茨海默病(AD)模型大鼠脑内Caspase-3表达与活性变化及反式转录激活因子-X连锁凋亡抵制蛋白(TAT-XIAP)融合蛋白的干预作用.方法:SD大鼠随机分为盐水对照组、AD模型组及治疗组,采用双侧海马内注射Aβ25-35建立AD模型,造模后6周尾静脉注射TAT-XIAP融合蛋白,连续给药4周后处死动物,通过RT-PCR和免疫组织化学研究AD大鼠大脑皮质与海马Caspase-3 mRNA表达及蛋白的活性变化,TATXIAP融合蛋白对上述作用的干预.结果:AD模型组大鼠大脑皮质与海马Caspase-3 mRNA表达上调,模型组大脑皮质和海马Caspase-3表达分别是对照组的2.03倍和1.72倍;活化的Caspase-3位于细胞核,AD模型组大鼠大脑皮质与海马Caspase-3蛋白活性增强,模型组大脑皮质和海马Caspase-3活性分别是对照组的1.62倍和1.64倍.应用TAT-XIAP融合蛋白后,大鼠皮质与海马Caspase-3表达与活性均降低;治疗组与模型组比较大脑皮质和海马Caspase-3表达分别下降了9％和44％,Caspase-3活性分别下降了36％和28％.结论:本实验结果表明Aβ25-35可上调Caspase-3 mRNA表达,活化Caspase-3;TAT-XIAP融合蛋白可抑制AD模型大鼠Caspase-3 mRNA的表达和活性.     

S14G-Humanin对Aβ_(31-35)所致大鼠行为学及神经元凋亡的影响

目的:研究S14G-Humanin对Aβ31-35所致大鼠行为学及神经元凋亡的影响。方法:SD大鼠60只随机分为5组,经侧脑室分别注入生理盐水(对照组)、Aβ31-35(Aβ31-35组),Aβ31-35+HNG(0.01 mmol/L),Aβ31-35+HNG(0.1 mmol/L)和Aβ31-35+HNG(1 mmol/L)。注射第7 d行Morris水迷宫实验观察各组大鼠的行为学改变;注射12 d后处死大鼠,应用TUNEL法检测各组海马神经元的凋亡情况,应用免疫组化法检测神经元caspase-3的表达。结果:与对照组相比,Aβ31-35组大鼠的学习、记忆能力明显下降(P<0.05),Aβ31-35+HNG(0.1,1 mmol/L)组大鼠的学习、记忆能力有所改善,与Aβ31-35组相比差异有统计学意义(P<0.05)。Aβ31-35组海马神经元的凋亡指数及caspase-3阳性细胞数均高于正常对照组,Aβ31-35能引起大鼠海马神经元的凋亡及学习、记忆能力的下降;Aβ31-35+HNG(1,0.1,0.01 mmol/L)组凋亡指数及caspase-3阳性细胞数均明显下降,与Aβ31-35组相比差异有统计学意义(P<0.05)。结论:S14G-Humanin对Aβ31-35诱导的大鼠海马神经元凋亡及行为学改变具有保护作用。     

纳米水平分子成像与诊疗一体化研究进展与挑战

分子成像能以非侵入性的方式重现活体细胞的生理功能和生物学过程,提高疾病的早期和特异性诊断水平。纳米颗粒/材料具有物理性质可控性高、易于表面修饰、血液循环时间长和可功能化等优点,在疾病诊断与治疗中显示出巨大潜力。但如何阐明纳米材料多功能间的内在联系、解决其代谢及安全性等关键机制难题、实现纳米颗粒/材料多功能性到临床多功能...     

Alterations of regular and mature monocytes are distinct,and dependent of intensity and duration of exercise

Circulating monocytes comprise functionally distinct regular (CD14^bright+) and mature (CD141^low+) cells. Cell surface receptors were determined by three colour flow cytometry in 8 healthy control subjects. Compared to regular monocytes, mature monocytes had lower levels of the high affinity Fcy receptor 1 (CD64), complement receptor 3 (CDllb), CD45RO and higher levels for HLA-DR, LFA-1 (CD11a/CD18), interleukin-2 receptor (CD25), CD45RA and the Fc receptor 3 (CD16). Both regular and mature monocytes were measured before and up to three hours after four different types of exercise (Ex) in endurance trained athletes (n=9-16). Immediately after anaerobic exercise of I min with a maximal lactate concentration (la_max) of I2.3 (SD I.4) mmol · l^–1 and exhaustive exercise of 24 (SD 8) min with a maximal lactate concentration (la_max) of 7.4 (SD 2.6) mmol· l^–1 mature monocytes increased more than regular monocytes. Exhaustive endurance exercise of 87 (SD 21) min [la_max 3.7 (SD I.0)] led to a similar increase of regular and mature monocytes. 15–33 min after a 100km run regular monocytes increased significantly, whereas mature monocytes decreased. Up to three hours after the end of all exercises mature monocytes fell below pre-exercise values. In conclusion, duration and intensity of exercise alter distinct maturation stages of monocytes differently. It is probable that the avidity of adhesion molecules like LFA-1 to their endothelial ligands is increased to enable the firm attachment to the endothelium.     

Association between functional alterations of senescence and senility and disorders of gait and balance

OBJECTIVES:

Declines in cognition and mobility are frequently observed in the elderly, and it has been suggested that the appearance of gait disorders in older individuals may constitute a marker of cognitive decline that precedes significant findings in functional performance screening tests. This study sought to evaluate the relationship between functional capacities and gait and balance in an elderly community monitored by the Preventive and Integrated Care Unit of the Hospital Adventista Silvestre in Rio de Janeiro, RJ, Brazil.

METHODS:

Elderly individuals (193 females and 90 males) were submitted to a broad geriatric evaluation, which included the following tests: 1) a performance-oriented mobility assessment (POMA) to evaluate gait; 2) a mini-mental state examination (MMSE); 3) the use of Katz and Lawton scales to assess functional capacity; 4) the application of the geriatric depression scale (GDS); and 5) a mini-nutritional assessment (MNA) scale.

RESULTS:

Reductions in MMSE, Katz and Lawton scores were associated with reductions in POMA scores, and we also observed that significant reductions in POMA scores were present in persons for whom the MMSE and Katz scores did not clearly indicate cognitive dysfunction. We also demonstrated that a decline in the scores obtained with the GDS and MNA scales was associated with a decline in the POMA scores.

CONCLUSIONS:

Considering that significant alterations in the POMA scores were observed prior to the identification of significant alterations in cognitive capacity using either the MMSE or the Katz systems, a prospective study seems warranted to assess the predictive capacity of POMA scores regarding the associated decline in functional capacity.     

Triptorelin and cetrorelix induce immune responses and affect uterine development and expressions of genes and proteins of ESR1, LHR,and FSHR of mice

Context: GnRH immunity can reduce the expression of pituitary GnRH levels, and cause the changes in reproductive behaviors. It is unclear whether triptorelin (TRI) and cetrorelix (CET) immunity influences uterine development and expression of follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), and estradiol receptor 1 (ERS1) in the uterus.

Objective: The study investigated the effects of active immunity of GnRH agonist and antagonist on uterine development, microstructures, expression of hormone receptors mRNAs, and proteins in uteri.

Materials and methods: One hundred and five mice were assigned into CET, TRI, and control groups (CG). Mice in CET-1, CET-2, and CET-3 (n?=?15) were subcutaneously injected with 10, 20, and 40?μg CET antigens for seven days, respectively. Mice in TRI-1, TRI-2, and TRI-3 were injected with 10, 20, and 40?μg TRI antigens for seven days, respectively. The qPCR and Western blot were implemented to determine expressions of ESR1, LHR and FSHR mRNAs, and proteins.

Results: Compared with CG, the uterine weights of CET-1, CET-2, and CET-3 increased by 42.86, 62.86, and 10.00% on day 35 (p?p?p?p?p?Conclusions: CET immunity promoted the uterine development, improved EET and UWT, and also promoted the expressions of ESR1 and FSHR protein levels. It lessened the LHR protein levels. TRI immunity blocked EET and UWT, inhibited uterine growth and development. The efficacy of CET immunity was more obvious than TRI.     

韧带和肌腱的生物力学和力学生物学研究

国际韧带和肌腱研讨会(The International Symposium on Ligaments and Tendons,ISI&T)于2000年在美国佛罗里达州奥兰多市首次召开。研讨会的宗旨是引起对韧带和肌腱研究的重视,并为生物工程师、生物学家、临床医师提供一个可以分享、评论、讨论韧带和肌腱最新研究成果的论坛。从2000年起,国际韧带和肌腱研讨会已经开展了15届;每届研讨会上涌现了大量令人振奋的关于当前韧带和肌腱研究热点和未来挑战的讨论。多年来,韧带和肌腱领域内的研究数量大幅增加,研究质量不断提升。为纪念《医用生物力学》杂志创刊30周年,本文总结过去30年里韧带和肌腱研究的主要进展,包括组织力学、力学生物学、损伤与治愈机制、组织修复和再生。     

Morphology and cytochemistry of leucocytes and thrombocytes of six species of fish

Cytochemical reactions of blood leucocytes and thrombocytes from six species of fish, rainbow trout (Onchorhynchus mykiss), coho salmon (Onchorhynchus kisutch), white sturgeon (Acipenser transmontanus), goldfish (Carassius auratus), striped bass (Morone saxatulis), and channel catfish (Ictalurus punctatus) were determined. Because the staining reactions were generally similar to the reactions found in mammalian leucocytes with similar morphological features, it is reasonable to classify fish leucocytes using the same terminology as is used for mammalian leucocytes. However, in some species leucocytes with features similar to mammalian eosinophils or basophils were not found. In goldfish leucocytes were found that had segmented nuclei and unstained, moderately refractile cytoplasmic granules. These cells were classified as segmented, granular leucocytes. Although these cells do not appear similar to any mammalian or avian leucocyte, the pattern of positive cytoplasmic alkaline phosphatase staining and negative granular staining is similar to that of equine eosinophils.     

男性乳腺发育症临床病理分析及雌,孕激素受体检测

对１１３例男性乳腺发育症进行临床病理分析。同时检测其中３０例乳腺组织中雌激素受体和孕激素受体分布情况，结果发现两者阳性率分别为８０．０％和８３．３３％。结合文献讨论了男性乳腺发育症的发生与高血清激素浓度及乳腺组织高受体水平的关系。     

Pathology and genetics of phaeochromocytoma and paraganglioma

Phaeochromocytoma and paraganglioma (PHEO/PGL) are rare tumours with an estimated annual incidence of 3 per million. Advances in molecular understanding have led to the recognition that at least 30–40% arise in the setting of hereditary disease. Germline mutations in the succinate dehydrogenase genes SDHA, SDHB, SDHC, SDHD and SDHAF2 are the most prevalent of the more than 19 hereditary genetic abnormalities which have been reported. It is therefore recommended that, depending on local resources and availability, at least some degree of genetic testing should be offered to all PHEO/PGL patients, including those with clinically sporadic disease. It is now accepted that that all PHEO/PGL have some metastatic potential; therefore, concepts of benign and malignant PHEO/PGL have no meaning and have been replaced by a risk stratification approach. Although there is broad acceptance that certain features, including high proliferative activity, invasive growth, increased cellularity, large tumour nests and comedonecrosis, are associated with an increased risk of metastasis, it remains difficult to predict the clinical behaviour of individual tumours and no single risk stratification scheme is endorsed or in widespread use. In this review, we provide an update on advances in the pathology and genetics of PHEO/PGL with an emphasis on the changes introduced in the WHO 2017 classification of endocrine neoplasia relevant to practising surgical pathologists.