低氧预适应小鼠脑组织内P38 MAPK磷酸化水平增高

目的探讨P38丝裂原激活蛋白激酶(mitogen-activated protein kinase,P38 MAPK)在小鼠脑低氧预适应形成过程中的作用。方法用成年雄性BALB/c小鼠制备小鼠整体低氧预适应模型,小鼠随机分为正常对照(H0)、早期(H1～H4)和延迟性(H5～H6)低氧预适应等7组;应用Westernbolt并结合GelDoc凝胶成像系统,定量检测小鼠脑组织内P38MAPK磷酸化水平和蛋白表达量。结果与H0组小鼠相比,H2~H6组的海马和皮层及H3～H6组的下丘脑中P38MAPK磷酸化水平明显增高(P<0·05,每组n=6);H1~H6组的皮层、海马和下丘脑中P38MAPK蛋白表达量无明显变化。结论P38MAPK磷酸化激活而非蛋白表达量的变化可能参与了小鼠脑低氧预适应的发生、发展过程。     

低氧预适应鼠脑海马组织内与cPKCγ相互作用的ERK1/2磷酸化水平降低

目的探讨与经典型蛋白激酶Cγ(cPKCγ)相互作用的细胞外信号调节激酶1/2(ERK1/2)的磷酸化水平在小鼠脑低氧预适应形成过程中的变化。方法用成年雄性BalB/c小鼠制备整体低氧预适应模型,将小鼠随机分为正常对照(H0)、早期低氧预适应(H3)和延迟性低氧预适应(H6)3组。应用免疫共沉淀,Western blot等方法检测胞质和膜相关成分中与cPKCγ相互作用的ERK1/2的磷酸化水平。结果小鼠海马组织中ERK1/2能与cPKCγ免疫共沉淀,且与H0组相比,H3及H6组ERK1/2的204位酪氨酸磷酸化水平明显降低(P<0.05)。结论小鼠海马组织中,cPKCγ与ERK1/2存在相互作用,且可能参与了脑低氧预适应的发生和发展。     

低氧预适应升高小鼠脑内JNK磷酸化水平和蛋白表达

目的探讨C-JUN氨基末端激酶或应激激活蛋白激酶(JNKs/SAPKs)在脑低氧预适应发生、发展过程中的作用。方法将小鼠整体低氧预适应模型中BALB/C小鼠随机分为正常对照(H0)、早期(H1~H4组)和延迟性(H5~H6组)低氧预适应等7组。应用SDS-PAGE和Western bolt方法,并结合Gel Doc凝胶成像系统,半定量检测大脑皮层和海马组织内JNK1和JNK2/3的磷酸化水平及其蛋白表达量的变化。结果在早期低氧预适应形成过程中,随低氧次数的增加,小鼠大脑皮层和海马组织内JNK1的磷酸化水平(未检测到磷酸化的JNK2/3)逐渐升高,且以皮层内(H1和H2组)和海马组织内(H1~H4组)的增高明显(P<0.05,n=6);而JNK1和JNK2/3只在延迟性低氧预适应(H5~H6组)发展过程中明显上调(P<0.05,n=6)。结论JNK1的激活以及JNK1和JNK2/3蛋白表达量的增高可能分别参与了脑早期低氧预适应和晚期延迟性低氧预适应的发生和发展。     

低氧预适应鼠脑内MSK1磷酸化水平的变化

目的:初步探讨丝裂原和应激激活的蛋白激酶1(mitogen-and stress-activated protein kinase 1,MSK1)在脑低氧预适应(HPC)发生发展过程中的作用。方法:按我们已建小鼠整体HPC模型,将健康成年BALB/c小鼠(18～22g,雄性)随机分为正常对照(H0)、早期(H1-H4)和延迟性(H5-H6)HPC等7组(每组n=6)。应用SDS-PAGE和Western blot技术,并结合Gel Doc凝胶成像系统,定量检测小鼠脑海马和皮层组织内MSK1第645位苏氨酸(p-Thr645-MSK1)和第375位丝氨酸(p-Ser375-MSK1)的磷酸化水平,以及MSK1总蛋白表达量的变化。结果:在脑早期(H1-H4)和延迟性(H5-H6)HPC形成过程中,随重复性低氧暴露次数的增加,H1-H6组小鼠海马和皮层组织内p-Thr645-MSK1及p-Ser375-MSK1的磷酸化水平较正常对照组(H0)显著增高(P<0.05);然而,小鼠海马和皮层组织内MSK1总蛋白表达量在H0-H6组中无明显变化。结论:MSK1磷酸化水平增高可能参与了小鼠脑HPC的发生发展过程。     

低氧预适应小鼠脑组织内CaMKⅡ磷酸化水平增高

目的探讨钙调蛋白依赖性蛋白激酶(CaMKⅡ)在小鼠脑低氧预适应(HPC)发生发展中的作用。方法成年雄性BALB/c小鼠随机分为正常对照(H0)、早期(H1～H4)和延迟性(H5～H6)低氧预适应等共计7组,制备小鼠HPC模型;用Western blot并结合GelDoc凝胶成像系统,检测小鼠脑组织内CaMKⅡ磷酸化水平和蛋白表达量;用免疫组化检测小鼠脑皮层和海马CaMKⅡ磷酸化水平。结果与H0组小鼠相比,H3～H5组海马和皮层的CaMKⅡ磷酸化水平明显升高(P<0.05);而H1～H6组的皮层和海马的CaMKⅡ蛋白表达量无明显变化;H3、H6组皮层和海马p-CaMKⅡ阳性细胞数目增多和灰度增强。结论CaMKⅡ磷酸化水平的升高可能参与了小鼠脑HPC的发生发展过程。     

低氧预适应鼠脑内核糖体S6激酶磷酸化水平和蛋白表达量的变化

探讨核糖体S6激酶(ribosomal S6kinase,RSK)Ser221(PDK1磷酸化位点)和Thr359/Ser363(ERK1/2磷酸化位点)的磷酸化水平以及总RSK蛋白表达量在小鼠脑低氧预适应发生发展过程中的变化。将成年雄性BALB/c小鼠(18～22g)随机分为正常对照(H0)和重复性低氧1～4次(H1～H4)等5组(每组n=6)。应用蛋白凝胶电泳(SDS-PAGE)和蛋白印迹(Western blot)技术,定量检测整体低氧预适应小鼠海马和皮层组织内Ser221位点(p-Ser221 RSK)和Thr359/Ser363位点(p-Thr359/Ser363 RSK)的磷酸化水平以及总RSK蛋白表达量。结果表明,随着低氧暴露次数增加,小鼠海马和皮层组织内p-Ser221 RSK磷酸化的水平显著增高(P<0.05,n=6),伴随着p-Thr359/Ser363 RSK磷酸化的水平明显降低(P<0.05,n=6);而RSK总蛋白的表达量则无明显改变。结果提示,Ser221 RSK磷酸化水平增高和Thr359/Ser363 RSK磷酸化水平降低可能参与了小鼠脑低氧预适应的发生发展过程。     

延迟性低氧预适应降低小鼠脑皮质cPKCγ蛋白表达

目的探讨cPKCα和γ膜转位水平及蛋白表达量在延迟性脑低氧预适应形成过程中的变化。方法应用SDS-PAGE和Western bolt等技术,并结合Gel Doc凝胶成像系统,半定量检测延迟性脑低氧预适应小鼠(H5和H6组)脑组织内cPKCα和γ的膜转位水平及蛋白表达量。结果延迟性低氧预适应(H5和H6组)明显降低小鼠脑皮质组织内cPKCγ蛋白表达量(P<0.05),而膜转位(活性)水平变化不显著。对海马cPKCγ、大脑皮质和海马cPKCα蛋白表达量及膜转位水平的影响均不显著。结论大脑皮质cPKCγ蛋白表达量的改变可能参与延迟性脑低氧预适应形成,且可能与皮质和海马低氧选择易损性的差异有关。     

重复性低氧增高小鼠脑组织内CREB的磷酸化水平

为探讨cAMP反应元件结合蛋白(CREB)在小鼠脑低氧预适应形成过程中的作用,本研究应用Westernblot技术结合GelDoc凝胶成像系统,半定量检测了整体低氧预适应模型小鼠脑组织内CREB的磷酸化水平和非磷酸化水平的表达水平。结果显示:(1)随低氧暴露次数(H1H4)的增加,小鼠海马组织内CREB的磷酸化水平(激活程度)明显增高(P<0.05;n=7);同样,大脑皮层内CREB的磷酸化水平也随低氧暴露次数(H1H4)的增加而明显增高(P<0.05,n=7);(2)随低氧暴露次数(H1H4)的增加,CREB的蛋白表达量无论在小鼠海马组织还是皮层组织内均无明显变化。以上结果提示CREB磷酸化水平的增高(激活)可能参与了脑低氧预适应的形成过程。     

低氧预适应后小鼠海马神经肽Y及突触的变化

目的 探讨低氧预适应产生神经保护作用的机制。方法 将小鼠随机分为对照组（H0组）和低氧组（H4组）,H4组为通过整体重复低氧建立的小鼠低氧预适应动物模型,H0组不进行低氧处理。用免疫组织化学方法检测小鼠海马神经肽Y(NPY)及突触体素（SYP）的表达,电镜观察海马CA1区的不对称突触和穿通型不对称突触形态及数量。结果 与H0组相比较,H4组海马NPY阳性细胞数量有中等量增多(n=30),SYP阳性细胞数量有明显增多(n=30),而海马CA1区的不对称突触和穿通型不对称突触数量减少(n=6)。结论 低氧预适应后海马的这些变化可能降低了神经元的兴奋性,从而增强了脑抵抗低氧/缺血的能力而产生神经保护作用。     

Level of functioning of siblings and parents of probands of varying degrees of retardation

A further analysis of already published data supports the position that retardates of low ability level less frequently have retarded siblings, retarded parents, and parents low in occupational level than do retardates higher in ability level. The analysis supports the position that there are two types of retarded individuals, persons retarded as a result of gene or chromosomal anomalies, brain injury, etc., who more frequently occur in the lower-level retardate group, and persons whose retardation represents polygenic segregation, who more frequently occur in the higher-level group.     

Modes of Inheritance of Errors of Refraction

Eighteen families in which both parents had refractions within the range of +4·0 D to −4·0 D and axial lengths seen in emmetropia (22·3-26·0 mm) showed coefficients of correlation of the order 0·5 indicative of polygenic inheritance. Such coefficients were seen for axial length (0·407) and for the cornea (0·487), but not for the lens (which is known to be yoked to the axial length). No such coefficients were seen in 19 families in which one of the parents had axial length outside the emmetropic range (nine families with long axes and 10 with short axes).

The pattern of polygenic inheritance for emmetropia (completely correlated optical components) and errors of refraction up to 4·0 D (inadequately correlated components: correlation ametropia) follows that seen in stature and other measurable characters. In contrast the high refractive errors with their abnormal axial lengths (component ametropia) are—like the extremes in stature—pathological anomalies with monofactorial inheritance.

     

Aspects of the problem of direct introduction of Standards of International Organizations

Editorial note. This article is published as part of a discussion. Particular issues of the article are disputable. First of all, this concerns the so-called “folder” method of introduction of international standards for medical devices to domestic medical practice (i.e., by direct translation of the standards and their publication as standardizing documents). Nevertheless, at least one of the problems, the problem of coordination between domestic state standards for medical devices and international recommendations of ISO and IEC, is undoubtedly of topical importance. Advancement of new health service legislation which is to be approved by law-makers will definitely introduce corrections into the present situation. The Editorial Board of Meditsinskaya Tekhnika believes this article will lessen these problems and to be welcomed by readers.