锰对大鼠睾丸支持细胞骨架蛋白及紧密连接相关蛋白表达的抑制作用

目的研究染锰诱导的大鼠睾丸超微结构改变及支持细胞(vimentin,VM)和紧密连接Occludins、Claudin-11mRNA表达,探讨锰对支持细胞骨架蛋白和紧密连接蛋白的破坏机制。方法雄性SD大鼠随机分为空白对照组,低剂量(15 mg/kg MnCl_2)和高剂量(30 mg/kg MnCl_2)组,8只/组。实验组分别染锰4周和6周,空白对照组给予等容生理盐水,给药途径均为腹腔注射,电镜观察睾丸支持细胞及血睾屏障超微结构,免疫组织化学(SABC)法检测支持细胞VM表达,实时定量PCR反应检测血睾屏障紧密连接Occludins和Claudin-11 mRNA表达。结果 1与空白对照组比较,各染锰组支持细胞数量及VM阳性细胞率、Occludins mRNA和Claudin-11 mRNA表达均显著降低。2染锰剂量相同,6周与4周组比较,以及染锰时间相同,高剂量组与低剂量组比较,支持细胞数量及VM阳性细胞率、Occludins mRNA和Claudin-11 mRNA表达均显著降低。3各组大鼠睾丸支持细胞数量与VM阳性细胞率及Occludins mRNA和Claudin-11 mRNA表达均成正相关。结论锰可抑制大鼠睾丸支持细胞骨架蛋白及紧密连接相关蛋白表达,破坏血睾屏障,导致生精微环境改变,产生生殖毒性效应。     

支持细胞波形蛋白及紧密连接结构蛋白在染锰大鼠睾丸中的表达

目的研究染锰诱导的大鼠睾丸超微结构改变及支持细胞vimentin(VM)和紧密连接Occludins mRNA和Claudin-11 mRNA表达,探讨锰对支持细胞骨架蛋白和紧密连接蛋白的破坏机制。方法雄性SD大鼠随机分为空白对照组,低剂量(15 mg/kg MnCl_2)和高剂量(30 mg/kg MnCl_2)组,8只/组。实验组分别染锰4周和6周,空白对照组给予等容生理盐水,给药途径均为腹腔注射,电镜观察睾丸支持细胞及血睾屏障超微结构,免疫组织化学(SABC)法检测支持细胞VM表达,实时定量PCR反应检测血睾屏障紧密连接Occludins,Claudin-11 mRNA表达。结果随着染锰时间延长和剂量增加,各组支持细胞数量及VM阳性细胞率、Occludins mRNA和Claudin-11 mRNA表达水平均显著降低。各组大鼠睾丸支持细胞数量与VM阳性细胞率及Occludins mRNA和Claudin-11 mRNA表达水平均成正相关。结论锰可抑制大鼠睾丸支持细胞骨架蛋白及紧密连接相关蛋白表达,产生生殖毒性效应。     

锰诱导大鼠生精细胞凋亡过程中半胱氨酸酶-3mRNA与增殖细胞核抗原表达变化

目的:研究氯化锰对生精细胞凋亡过程半胱氨酸酶3(caspase-3)mRNA和增殖细胞核抗原(PCNA)表达的影响,探讨两者在生精细胞凋亡过程中的作用。方法:雄性SD大鼠随机分为空白对照组、低剂量(15 mg/kg MnCl_2)和高剂量(30mg/kg MnCl_2)组。MnCl_2组分别染锰4周和6周,空白对照组给予等容生理盐水,给药途径均为腹腔注射,TUNEL法检测睾丸生精细胞凋亡,原位杂交和免疫组织化学(SABC)检测生精细胞caspase-3 mRNA和PCNA和表达。结果:与空白对照组比较,各染锰组生精细胞凋亡指数(AI)均升高,caspase-3 mRNA阳性细胞率均显著升高,染锰4周:PCNA阳性细胞率显著降低,染锰6周反而升高。染锰剂量相同,6周与4周组比较,生精细胞AI与caspase-3 mRNA阳性细胞率、PCNA阳性细胞率均显著升高。染锰时间相同,高剂量组与低剂量组比较,生精细胞AI与caspase-3 mRNA阳性细胞率均显著升高,PCNA阳性细胞率显著降低。各组大鼠生精细胞AI与caspase-3 mRNA阳性细胞率呈正相关,与PCNA阳性细胞率呈负相关,而caspase-3 mRNA阳性细胞率与PCNA阳性细胞率呈负相关。结论:锰可诱导大鼠生精细胞caspase-3mRNA表达,促使生精细胞凋亡并且抑制细胞增殖,产生生殖毒性效应。     

染锰大鼠生精细胞半胱氨酸蛋白酶3的表达及锌的保护作用

目的:研究氯化锰对生精细胞半胱氨酸蛋白酶3(caspase-3)表达的影响,探讨锰诱发大鼠生精细胞caspase-3表达的机制及锌的拮抗作用.方法:雄性SD大鼠随机分为空白对照组,ZnCl_2对照组,15mg/kg和30mg/kg MnCl_2组;15mg/kg和30mg/kg MnCl_2+ZnCl_2组.免疫组织化学法检测睾丸caspase-3表达.结果:各染锰组,染锰补锌组及染锰剂量相同的6周组,染锰时间相同的30mg/kg MnCl_2组caspase-3阳性细胞率均显著升高,染锰补锌组显著降低.结论:染锰15mg/kg 4周可诱发大鼠生精细胞caspase-3表达,且随染锰时间和剂量的增加而增加,两者存在一定时间-效应和剂量-效应关系;摄入含锌100mg/kg的食物可拮抗锰诱发的生精细胞caspase-3表达.     

染锰大鼠生精细胞凋亡中caspase-3 mRNA、凋亡蛋白酶活化因子-1及多聚ADP核糖聚合酶的表达变化

目的:研究染锰诱导的大鼠生精细胞凋亡过程中,天冬氨酸特异性半胱氨酸酶-3(caspase-3)mRNA和凋亡蛋白酶活化因子-1(Apaf-1)、多聚ADP核糖聚合酶(PARP)的表达及其关系,探讨它们在生精细胞凋亡过程中的作用。方法:雄性SD大鼠,设立空白对照组、低剂量(15 mg/kg MnCl_2)和高剂量(30 mg/kg MnCl_2)组。实验组分别染锰4周和6周,空白对照组给予等容生理盐水,给药途径均为腹腔注射,TUNEL法检测生精细胞凋亡,原位杂交法和免疫组织化学法检测生精细胞caspase-3 mRNA、Apaf-1和PARP的表达。结果:与空白对照组比较,各染锰组生精细胞凋亡指数(AI)和caspase-3mRNA阳性细胞率均显著升高,Apaf-1和PARP阳性细胞率均显著降低。染锰剂量相同,6周与4周组比较,以及染锰时间相同,高剂量组与低剂量组比较,生精细胞AI和caspase-3 mRNA阳性细胞率均显著升高,Apaf-1和PARP阳性细胞率均显著降低。各组大鼠生精细胞AI与caspase-3 mRNA阳性细胞率呈正相关,与Apaf-1和PARP阳性细胞率呈负相关。结论:锰可影响大鼠生精细胞caspase-3 mRNA表达,促进Apaf-1和PARP分解,导致生精细胞凋亡,产生生殖毒性效应。     

锰诱导大鼠生精细胞凋亡过程中生殖激素和乳酸脱氢酶及PARP的作用

目的研究锰对大鼠体内生殖激素和乳酸脱氢酶(LDH)和多聚ADP核糖聚合酶(PARP)表达的影响,探讨它们在生精细胞凋亡过程中的作用。方法雄性SD大鼠48只,随机分为空白对照组,低剂量组和高剂量组,腹腔注射Mn Cl24周和6周,TUNEL法检测生精细胞凋亡,放射免疫测定血清睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)含量,化学比色测定血清和睾丸LDH含量。免疫组织化学法检测生精细胞PARP表达。结果各染锰组生精细胞凋亡指数、血清FSH、LH及LDH含量升高,血清T、睾丸LDH含量及PARP表达降低。结论锰可使大鼠T和睾丸LDH降低,FSH、LH和血清LDH活性升高,抑制大鼠生精细胞PARP表达,导致生精细胞凋亡。     

谷胱甘肽对染锰大鼠生精细胞凋亡与增殖的影响

目的:研究谷胱甘肽(GSH)对染锰大鼠生精细胞凋亡与增殖的作用及机制。方法:雄性SD大鼠48只随机分为6组,各组给锰途径为腹腔注射。采用TUNEL法检测生精细胞凋亡指数(AI);免疫组织化学法检测生精细胞增殖细胞核抗原(PCNA)表达。结果:与空白对照组比较,GSH对照组和15mg/kg GSH组生精细胞AI与生精细胞PCNA增殖指数(PI)均无显著性差异;与各自对应的单纯染锰组比较,15mg/kg GSH组和30mg/kg GSH组生精细胞AI均显著降低而PI均显著升高;30mg/kg组与15mg/kg组比较,生精细胞AI显著升高而PI显著降低;各组大鼠生精细胞AI和PI呈负相关。结论:15mg/kg和30mg/kg氯化锰可诱发大鼠睾丸生精细胞凋亡,两者存在剂量-效应关系;各组大鼠睾丸生精细胞AI和PI呈显著负相关;GSH对锰诱发大鼠生精细胞凋亡具有拮抗作用;GSH可能拮抗锰对大鼠生精细胞增殖的抑制作用。     

锰对大鼠生精细胞Caspase-3 mRNA调控及支持细胞波形蛋白表达的影响

目的 探讨锰对大鼠生精细胞Caspase-3 mRNA调控及支持细胞波形蛋白（vimentin）表达的影响。 方法 将正常雄性SD大鼠48只,随机分为1个对照组和2个染锰组,给予各组大鼠腹腔注射生理盐水和15mg/kg、30mg/kg氯化锰。分别染锰4周和6周,随机处死各组大鼠8只。应用末端脱氧核糖核酸转移酶介导的dUTP缺口末端标记技术（TUNEL） 、原位杂交法和免疫组织化学链酶亲和素生物素过氧化物酶复合物（SABC）法进行检测研究。 结果 1. 与空白对照组比较,15mg/kg、30mg/kg染锰组生精细胞凋亡指数（AI）均升高（ P<0.05, P<0.01）,Caspase-3 mRNA阳性细胞率均显著升高（ P<0.01）,支持细胞波形蛋白（vimentin）阳性细胞率均显著降低（ P<0.01）。2. 染锰剂量相同,染锰6周组与染锰4周组比较,生精细胞AI与Caspase-3 mRNA阳性细胞率均显著升高（ P<0.01）,支持细胞vimentin阳性细胞率均显著降低（ P<0.01）。3. 染锰时间相同,30mg/kg MnCl2组与15mg/kg MnCl2组比较,生精细胞AI与Caspase-3 mRNA阳性细胞率均显著升高（ P<0.01）,支持细胞vimentin阳性细胞率均显著降低（ P<0.01）。4. 各组大鼠生精细胞AI和Caspase-3 mRNA阳性细胞率呈正相关（ r =0.842, P<0.01）,与支持细胞vimentin阳性细胞率呈负相关（ r =-0.859, P<0.01）,各组大鼠生精细胞Caspase-3 mRNA阳性细胞率和支持细胞vimentin阳性细胞率呈负相关（ r =-0.975, P<0.01）。 结论 染锰大鼠生精细胞Caspase-3 mRNA表达增加导致生精细胞凋亡增加;支持细胞vimentin表达下降;这可能是锰生殖毒性的重要分子机制之一。     

Caspase-3mRNA与PARP在染锰大鼠生精细胞中表达变化

目的研究氯化锰对生精细胞凋亡过程半胱氨酸酶3(caspase-3)mRNA和多聚ADP核糖聚合酶(PARP)表达的影响,探讨氯化锰的生殖毒性效应及可能机制。方法雄性SD大鼠48只随机分为空白对照组,低剂量(15 mg/kg MnCl_2)和高剂量(30 mg/kg MnCl_2)组,8只/组。MnCl_2组分别染锰4周和6周,空白对照组给予等容生理盐水,给药途径均为腹腔注射,TUNEL法检测睾丸生精细胞凋亡,原位杂交法和免疫组织化学(SABC)法检测生精细胞caspase-3mRNA和PARP和表达。结果随染锰时间延长和剂量增加,各染锰组生精细胞凋亡指数(AI)及caspase-3 mRNA表达水平显著升高,PARP表达水平显著降低,凋亡指数AI分别与caspase-3 mRNA和PARP表达呈正相关和负相关。结论锰可诱导大鼠生精细胞caspase-3 mRNA表达,促进PARP分解,导致生精细胞凋亡,产生生殖毒性效应。     

Caspase-9与Apaf-1在锰中毒大鼠生精细胞表达及XIAP与Smac的调控作用

目的研究氯化锰导致的大鼠生精细胞caspase-9及Apaf-1表达中XIAP和Smac的调节机制,探讨锰导致的雄性不育机制。方法雄性SD大鼠随机分为对照组,低剂量(15 mg/kg Mn Cl2)和高剂量(30 mg/kg Mn Cl2)组,腹腔注射MnCl24周和6周,免疫组织化学检测生精细胞caspase-9、Apaf-1、XIAP和Smac表达。结果各组生精细胞caspase-9、Apaf-1和Smac表达均显著升高,XIAP表达降低;同时间的高剂量组与低剂量组比较,同剂量的6周组与4周组比较,生精细胞caspase-9、Apaf-1和Smac表达均显著升高,XIAP表达降低;各组caspase-9与Apaf-1表达正相关,XIAP与Smac表达成负相关。结论锰可促进生精细胞caspase-9、Apaf-1和Smac表达,抑制XIAP表达,导致细胞凋亡,产生雄性生殖毒性效应。     

Co-ordination of cough and swallow in vivo and in silico

Coughing and swallowing are airway-protective behaviours. The pharyngeal phase of swallowing prevents aspiration of oral material (saliva, food and liquid) by epiglottal movement, laryngeal adduction and clearing of the mouth and pharynx. Coughing is an aspiration-response behaviour that removes material from the airway. Co-ordination of these behaviours is vital to protect the airway from further aspiration-promoting events, such as a swallowing during the inspiratory phase of coughing. The operational characteristics, primary strategies and peripheral inputs that co-ordinate coughing and swallowing are unknown. This lack of knowledge impedes understanding and treatment of deficits in airway protection, such as the co-occurrence of dystussia and dysphagia common in Parkinson's and Alzheimer's diseases, as well as stroke.     

Incorporation and Disappearance of Sulfate in Different Regions of Mouse and Rat Costal Cartilage in vivo and in vitro

A rapid and simple method for liquid scintillation counting of ³³S-sulfate in biological tissues is described. Sulfate incorporation per mg dry weight into selected lateral, medial and intermediate regions of ribs was studied using costal cartilage from rats and mice. In vitro, cartilage pieces embracing the osteochondral junction had 2–4 times larger incorporation rate than the remaining homogeneous parts of the ribs, both if entire rib cages or stripped and diced cartilage were incubated. After in vivo injection to rats and mice the incorporation rates of sulfate into the region of the osteochondral junction was 2.6 times that found in “resting” cartilage in rats and 4.4 times in mice. The ³⁵S-sulfate uptake in the ribs per mg dry cartilage diminished in the caudal direction. Growth of the chest cage was mainly a longitudinal growth of the bony segments. Marked differences in the disappearance rates of previously incorporated sulfate were found in different regions along the rib. Rapid sulfate disappearance was found in the bony segment which, however, had incorporated only one seventh of the amount per mg taken up by “resting” cartilage. The “resting” cartilage segments exhibited a steady slow disappearance rate for sulfate and the osteochondral junction region consisting of several differently active tissues showed a rapid sulfate disappearance in the beginning followed by a slow clearance after 2 weeks similar to that of “resting” cartilage. The necessity of careful selection of costal cartilage samples with respect to regional differences is emphasized.     

An in vivo and in vitro study of selenium deficiency and infection in rats

Selenium deficiency in rats impairs the ability of neutrophils and peritoneal macrophages to kill Candida albicans organisms in vitro. In contrast, killing of Salmonella typhimurium and Staphylococcus aureus organisms is unaffected by the deficiency. Survival of rats after intraperitoneal injection of 8 X 10(7) S. aureus organisms was not affected by Se deficiency, but a 5-fold increase in the dose (4 X 10(8) S. aureus organisms) led to a significantly greater mortality in the Se deficient rats.     

Visualization and characterization of 5-HT receptors and transporters in vivo and in man

Ascending and descending efferent pathways from the nuclei of serotonergic neurones located in brainstem raphe nuclei project to all regions of the central nervous system. Therefore, in considering the major physiological roles played by this neurotransmitter system, it is not surprising that serotonin is implicated in the aetiologies of many CNS dysfunctions which underlie psychiatric and neurological disorders. The presynaptic serotonin uptake mechanism and the many receptor subtypes that mediate the neurotransmitter roles of serotonin have been, and continue to be, targeted by drug discovery programmes aimed at identifying improved therapies for CNS disorders. Here we review the radioligands available for the important task of visualizing and characterizing these targets in the living human brain using either positron emission tomography (PET) or single photon emission tomography (SPECT). Such studies are crucial for extending our knowledge of the involvement of serotonin neurotransmission in the aetiologies of these disorders and for the development of new and more effective therapies. Particularly important recent advances in the methodologies for imaging the 5-HT transporter, the 5-HT_2A receptor and the 5-HT_1A receptor will almost certainly lead to important clinical research into the changes occurring in serotonergic neurotransmission during the onset, progression and treatment of affective and neurodegenerative disorders.     

ALA和HMME水凝胶栓剂的制备和体内外释药研究

目的 制备光敏剂5-氨基酮戊酸(ALA)和血卟啉单甲醚(HMME)水凝胶栓剂,评价其对直肠肿瘤组织的光敏剂递送效率.方法 将皮下移植人直肠癌细胞SW837的BALB/c小鼠随机分为水凝胶栓剂直肠局部给药组、皮肤局部给药组、瘤内注射给药组和静脉注射给药组.用荧光光谱仪测量直肠壁、皮肤和皮下肿瘤中原卟啉(PpⅨ)和HMME的浓度,荧光光谱系统测定相应的光敏剂分布情况.结果 ALA水凝胶栓剂直肠局部给药组的PpⅨ浓度分别是皮肤局部给药组的9.76倍(1 h)和5.80倍(3 h),差异均具有统计学意义(均P＜0.05).皮肤局部给药后2h,ALA在肿瘤组织内达到最大穿透深度(3～6 mm).而HMME水凝胶栓剂直肠局部给药后,直肠壁中的HMME浓度极低,且皮肤局部给药后的最大肿瘤穿透深度不足2 mm.结论 与皮肤相比,ALA更易穿透黏膜屏障,以水凝胶栓剂形式直肠局部给药有望成为ALA用于光动力疗法治疗直肠癌的一种给药方式.     

高校组织学与胚胎学课程思政研究状况

<正>为了解我国高校组织学与胚胎学课程思政的开展情况。通过检索中国科学引文数据库、维普信息资源系统和万方数据库获得相关文献,从课程思政的基本概念和意义、组织学与胚胎学课程思政状况和展望3个方面进行了归纳。课程思政的提出,目的是为高校思想政治教育改革探索新模式。目前组织学与胚胎学课程思政工作主要从课程思政的目标、思政元素、方法、存在的问题和解决方法等方面开展了探索和研究。