Nω-硝基-L-精氨酸甲酯对大鼠严重烫伤血脑屏障损伤及脑水肿的影响

目的:观察Nω-硝基-L-精氨酸甲酯(L-NAME)对严重烫伤大鼠血脑屏障(BBB)通透性的影响,探讨NO在严重烫伤中损害BBB的机制.方法:实验SD大鼠分为烫伤组和L-NAME组后又各分为烫伤后1～24 h等5组.检测大鼠脑组织伊文蓝(EB)含量及脑百分含水量;观察BBB超微结构变化.结果:烫伤组与正常组比较,脑EB含量明显增高,具有显著差异.用L-NAME治疗后在1～12 h均可见明显的疗效,脑EB含量与同组比较明显下降.电镜显示:烫伤3 h以后脑毛细血管周围出现空泡化,内皮肿胀,基底膜厚薄不均;经L-NAME治疗后脑毛细胞血管基本恢复到正常.结论:严重烫伤可导致脑BBB通透性增高,早期应用L-NAME能明显减轻烫伤对脑BBB的损伤.     

电针预处理对MCAO大鼠模型血脑屏障和MMP-9的影响

目的:探讨电针(EA)预处理对大鼠脑缺血再灌注后血脑屏障(BBB)通透性及脑内基质金属蛋白酶-9(MMP-9)表达的影响。方法:96只成年雄性SD大鼠随机分为假手术(Sham)组、单纯电针(EA)组、缺血(MCAO)组及电针预处理(EA+MCAO)组,每组24只。使用线栓法制作大鼠大脑中动脉阻塞(MCAO)模型,缺血120 min再灌注48 h后处死取脑。分别采用干湿重法测定各组动物脑水含量,伊文斯蓝(EB)法检测血脑屏障通透性,Western Blot检测紧密连接蛋白(TJP)及MMP-9表达水平,同时明胶酶谱法检测MMP-9活性。结果:与Sham组相比,MCAO组大鼠脑水含量及EB含量增多(P0.05),缺血侧脑组织TJP水平下降(P0.05),MMP-9表达及活性明显升高(P0.05);与MCAO组大鼠比较,EA+MCAO组脑水含量及EB含量减少(P0.05),缺血侧脑组织TJP水平升高(P0.05),同时MMP-9表达及活性显著降低(P0.05)。结论:电针预处理通过抑制缺血后脑内MMP-9的表达及活性,维持BBB完整性,有效改善脑缺血后的脑水肿症状。     

丁苯酞预处理对脑缺血再灌注损伤大鼠基质金属蛋白酶-9、基质金属蛋白酶组织抑制因子-1和血脑屏障的影响

目的:探讨丁苯酞预处理对脑缺血再灌注损伤大鼠基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制因子-1(TIMP-1)和血脑屏障的影响.方法:90只雄性SD大鼠随机分为假手术组,模型组,NBP预处理低剂量组、中剂量组、高剂量组.采用线栓法制作大脑中动脉栓塞(MCAO)模型,缺血2h再灌注24 h后以干湿重法测定脑组织含水量,伊文思蓝(EB)评估血脑屏障的破坏程度,实时PCR检测MMP-9及TIMP-1 mRNA的表达水平.结果:脑缺血再灌注后,脑组织含水量及EB含量明显增加,MMP-9和TIMP-1表达均增强,与假手术组比较差异有统计学意义.丁苯酞预处理各组脑组织含水量及EB含量较模型组明显下降,MMP-9表达显著减少,TIMP-1表达明显增加,丁苯酞预处理中、高剂量组差异无统计学意义.结论:丁苯酞预处理对脑缺血再灌注损伤大鼠可通过调节MMP-9/TIMP-1的表达,降低血脑屏障通透性,减轻脑水肿,发挥预防性保护作用.     

MMP-9促进间充质干细胞穿越血脑屏障的作用研究

目的 探讨基质金属蛋白酶-9（MMP-9）开放血脑屏障（BBB）,促进大鼠间充质干细胞（rMSCs）穿越BBB的作用.方法 构建体外BBB模型,运用Transwell细胞迁移率实验明确MMP-9对体外BBB模型的穿透效果.体内实验：4周龄SD大鼠随机分为假手术组、缺氧缺血性脑损伤（HIBD）组、MMP-9处理组及MMP-9抑制剂（TIMP-1）干预组;HE染色观察各实验组不同时间点（0.5、1、3、7、14d）的大脑皮质病理变化和检测其脑含水量,EB值法检测BBB通透性;同时采用Western Blot测定大鼠皮质中MMP-9蛋白表达和免疫组织化学法测定大脑皮质内5-溴-2-脱氧嘧啶（Brdu）标记rMSCs阳性细胞数量.结果 Transwell细胞迁移率实验显示,缺氧状态下各组穿过小室的rMSCs数量均明显高于常氧,差异有统计学意义（P＜0.01）;MMP-9处理组穿过小室的rMSCs数量明显高于阴性对照组和TIMP-1干预组,差异有统计学意义（P＜0.01）.体内实验结果表明：与HIBD组相比,MMP-9处理组脑含水量、BBB通透性增加程度均有所提高;TIMP-1干预组的相应指标均有所降低.大鼠皮质中MMP-9蛋白表达水平具有时间依赖性,MMP-9处理组1～3 d时含量达到最高,明显高于HIBD组和TIMP-1干预组,差异有统计学意义（P＜0.01,P＜0.05）,之后表达开始回落,但仍有稳定表达.MMP-9处理组穿越BBB的Brdu阳性细胞数比HIBD组多,差异有统计学意义（P＜0.01,P＜0.05）.结论 大鼠缺氧缺血后MMP-9表达升高,可介导开放BBB,促进rMSCs穿越BBB.     

复方丹参对严重烫伤大鼠血脑屏障的保护作用

目的　观察复方丹参注射液对严重烫伤大鼠血脑屏障通透性及脑内ZO-1mRNA影响,探讨复方丹参对严重烫伤大鼠血脑屏障损伤的保护作用。 方法　将大鼠随机分成假烫伤组、烫伤组、复方丹参治疗组。紫外分光光度计检测各组大鼠脑组织内伊文氏蓝的含量,RT-PCR检测严重烫伤大鼠脑内ZO-1 mRNA表达变化。 结果　大鼠严重烫伤后3～48 h脑内ZO-1mRNA表达下降。脑内伊文氏蓝（EB）含量从烫伤后3h开始升高,在6～12 h显著升高。用复方丹参治疗后, 严重烫伤大鼠脑内EB含量降低,以3、6 h下降最明显（P<0.010）;脑内ZO-1mRNA表达升高,以烫伤3 h治疗组最为明显。 结论　复方丹参注射液可防止严重烫伤大鼠脑内ZO-1mRNA的下降,减轻严重烫伤对大鼠血脑屏障的损害。     

5-LO通路活化对大鼠脑缺血再灌注损伤致血脑屏障破坏的影响

为了研究大鼠局灶性脑缺血再灌注损伤(CIRI)后血脑屏障(BBB)通透性的改变,观察5-脂氧酶(5-LO)、白三烯(LTs)、核因子-κB(NF-κB)、基质金属蛋白酶-9(MMP-9)的表达变化,探讨5-LO通路活化参与BBB破坏的可能机制,本实验采用线栓法制备大鼠大脑中动脉闭塞2h/再灌注24h模型。伊文氏蓝示踪剂检测BBB的通透性;RT-PCR检测损伤侧脑组织5-LO mRNA、半胱氨酰白三烯受体1(CysLTR1)mRNA的表达;ELISA检测血清LTB4的含量;免疫组织化学法检测损伤侧脑组织5-LO、NF-κB、MMP-9蛋白的表达情况。结果显示:局灶性脑缺血2h/再灌注24h后,大鼠BBB的通透性明显增高,5-LO mRNA、CysLTR1 mRNA的表达以及血清LTB4的含量均增高;5-LO、NF-κB、MMP-9蛋白在脑组织内的表达亦显著增多。本研究结果提示,CIRI后5-LO通路活化可经CysLTR1、LTB4、NF-κB、MMP-9介导BBB破坏,继而引发级联反应,加重脑损伤。     

姜黄素对脑缺血再灌注模型大鼠的神经保护作用及其机制

目的:观察姜黄素对脑缺血再灌注大鼠模型的神经保护作用及其机制。方法:雄性SD大鼠随机分为3组:模型组、姜黄素组和假手术组,模型组采用血管内线栓阻断法制备大鼠局灶性脑缺血再灌注损伤模型,姜黄素组在缺血前1h腹腔注射姜黄素200mg/kg,随后每12h腹腔注射姜黄素60mg/kg(共5次)。再灌注后3h、24h和72h测定脑组织含水量、伊文斯蓝(EB)含量(反映血脑屏障破坏情况),免疫印迹法测定脑组织基质金属蛋白酶-9(MMP-9)表达水平。结果:脑缺血再灌注损伤大鼠脑组织含水量及EB含量增加,MMP-9高表达。姜黄素治疗能够减轻神经功能损伤,降低脑组织含水量和EB含量,并降低MMP-9表达水平(P<0.01)。结论:姜黄素通过降低脑缺血再灌注大鼠MMP-9表达水平及血脑屏障通透性,对脑缺血再灌注损伤起保护作用。     

雌激素对大鼠脑缺血再灌注后血脑屏障作用研究

目的观察雌激素对大鼠脑缺血再灌注后血脑屏障(blood-brain barrier,BBB)的通透性、Occludin表达的影响,探讨雌激素在脑缺血中的作用。方法随机将去势雌性大鼠分为假手术组、模型组、雌激素预处理组,选取缺血再灌后4 h,24 h,3 d3个时间点作为观察点,对各个时间点脑水肿情况、Occludin蛋白表达、血脑屏障通透性改变进行考察分析,并选取24 h和3 d作BBB超微结构电镜观察,脑水肿改变情况采用脑含水量百分数测定;蛋白质表达采用western blot方法;血脑屏障通透性改变采用伊文思蓝(EB)比色法。结果与假手术组比较,局灶性脑缺血再灌4 h模型组大鼠脑组织含水量及EB含量均增加(P0.05),随缺血再灌时间延长,脑组织含水量、脑组织EB含量持续增加,至24 h,达到高峰(P0.01),与同时间点模型组比较,各治疗组大鼠脑组织含水量、EB含量均有不同程度降低(P0.05或P0.01),以24 h组降低最为显著(P0.01)。电镜观察雌激素预处理组较模型组同时间点比较BBB TJ开放减轻,星形胶质细胞足突及毛细血管管周水肿较轻,以3 d组显著。Western blot检测Occludin蛋白表达,发现模型组4 h时Occludin蛋白表达较假手术组减弱,但无显著性差异(P0.05),24 h组Occludin蛋白表达较假手术组减弱,有显著性差异(P0.05),3 d组Occludin蛋白表达进一步减弱,有明显差异(P0.01),雌激素组4 h时Occludin蛋白表达较同时间点模型组比较无显著性差异(P0.05),雌激素24 h及3 d组Occludin蛋白表达较同时间点模型组比较均升高,有显著性差异(P0.05)。结论局灶性脑缺血大鼠动物血脑屏障超微结构可见紧密连接发生断裂,内皮细胞内小泡数量增加及星形胶质细胞足突肿胀,可能是大鼠局脑缺血时血管源性脑水肿的重要因素。大鼠局灶性脑缺血,随缺血再灌时间延长,紧密连接相关蛋白occludin的表达明显下降,提示occludin在调节紧密连接通透性变化的过程中有重要作用。雌激素上调紧密连接Occludin蛋白的表达,有可能是其维护血脑屏障完整性减轻脑水肿的机制之一。     

严重烫伤早期脑GFAP表达与突触变化

目的探讨严重烫伤早期星形胶质细胞形态学变化、GFAP表达与突触可塑性的影响。方法健康SD大鼠，随机分为正常组假烫伤组，烫伤组。烫伤后又设3、6、12、24、48h5个时相点，用透射电镜观察超微结构变化；免疫组化观察脑GFAP表达。结果烫伤后突触小泡减少，突触间隙增宽。脑GFAP表达增加。结论严重烫伤后星形胶质细胞活化、突触改变、GFAP表达增加与血脑屏障通透性增高有关。     

严重烫伤大鼠脑内MMP-9及NOS表达变化及意义

目的:观察严重烫伤大鼠脑内基质金属蛋白酶-9(MMP-9)及一氧化氮合酶(NOS)的表达变化,分析两者之间的关系及意义。方法:建立30%TBSAⅢ度烫伤SD大鼠模型,应用免疫组化法检测大鼠脑内MMP-9的表达变化,NADPH-d组织化学方法检测脑内NOS的表达变化,用干湿法检测脑百分含水量。结果:严重烫伤后脑百分含水量增高,以6～12h最为显著;烫伤后3hMMP-9阳性细胞数开始增多,12～24h阳性细胞数增加达高峰;48h阳性细胞数开始下降。大鼠严重烫伤后3,12,24h大脑皮质及烫伤后3,24h的纹状体内NOS阳性神经元数量明显增多。讨论:严重烫伤后脑内MMP-9和NOS均升高,可能与血脑屏障损害及脑水肿的形成有关。     

Recovery of responsiveness of cells of lateral geniculate nucleus of rat

1. Recovery of responsiveness of single cells in lateral geniculate nucleus of rat has been determined in both P and I cells. There are three types of recovery curve among P cells; (a) early recovery, (b) early partial recovery followed by depression and then complete recovery, (c) prolonged depression followed by cyclic recovery. Type (c) is by far the commonest recovery curve. In contrast to the spike in a P cell, the synaptic potential recovers to its full amplitude in about 20 msec. All I cells exhibit similar rapid recovery curves after a prolonged depression.2. Conditioning stimuli applied to visual cortex also produce a prolonged depression in most P cells but I cells can be re-excited at short intervals from cortex. Decortication does not prevent the prolonged depression of the multineuronal response produced by optic nerve stimulation.3. A neuronal model is proposed to explain these observations. It is supposed that I cells (interneurones) are innervated by axon collaterals of the P cells (principal cells, projecting to visual cortex) and that the I cells exert an inhibitory influence on the P cells.     

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.

     

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.     

Analysis of two types of dopaminergic responses of neurons of the spinal ganglia of rats

It was established, in experiments on isolated spinal ganglia of adult rats in concluons of intracellular recording, that dopamine (1 M/liter) elicits depolarized responses in 61% of neurons, hyperpolarized in 20% of neurons, and depolarized-hyperpolarized in 19% of neurons. The depolarized responses are associated with the activation of D₁ dopamine receptors, and are governed by the shift of cAMP-dependent cation (sodium) channels to the conducting state. The hyperpolarized responses are triggered by the activation of D₂ dopamine receptors, which by means of HTP-binding protein convert the potassium channels to the conducting state. The change in the polarization of neurons with the action of dopamine influences their electrical excitability variously.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 76, No. 6, pp. 739–745, June, 1990.