炎性介质阻断剂对大鼠脑缺血再灌注损伤后神经功能缺损、细胞凋亡及半胱氨酸蛋白酶-3表达的影响

目的探讨炎性介质阻断剂AG490对大鼠局灶性脑缺血再灌注损伤后神经功能缺损、细胞凋亡及半胱氨酸蛋白酶-3(caspase-3)表达的影响。方法雄性SD大鼠被随机分为假手术组、缺血再灌注组、生理盐水组、AG490组;采用大脑中动脉线栓法制作大鼠局灶性脑缺血再灌注模型;AG490组于脑缺血即刻及再灌注后12 h分别腹腔注射AG490 1 mg/kg。再灌注24 h后对各组大鼠进行神经功能缺损评分;利用原位缺口末端标记法(TUNEL法)检测神经细胞凋亡数;应用Western Blot法检测各组脑组织磷酸化酪氨酸蛋白激酶(P-JAK2)、磷酸化信号转导和转录激活因子(P-STAT3)、caspase-3表达。结果与缺血再灌注组及生理盐水组比较,AG490组大鼠神经功能缺损评分明显减低(均P<0.05);凋亡细胞数及P-JAK2、P-STAT3、caspase-3表达明显减少(均P<0.01)。结论AG490可阻断JAK2/STAT3细胞因子信号转导通路,有效抑制caspase-3表达,减轻缺血灌注损伤后神经细胞凋亡,改善神经功能缺损症状。     

JAK2/STAT3信号传导通路在脑缺血再灌注损伤中的作用

目的研究JAK2/STAT3信号通路在脑缺血再灌注损伤中的作用,探讨缺血性脑卒中新的治疗靶点。方法建立大鼠脑缺血再灌注模型,应用免疫组织化学染色检测P-JAK2、P-STAT3在梗死区的表达情况,Tunel法检测神经细胞凋亡情况,观察P-JAK2、P-STAT3的激活与细胞凋亡的相关性。结果脑缺血再灌注后6h可观察到少量P-JAK2表达,24h开始明显增加,3d达到高峰后开始下降。而P-STAT3则于24h达到表达的高峰。给予P-JAK2抑制剂后,P-JAK2、P-STAT3的表达均发生下调,梗死区细胞凋亡数量减少。结论脑缺血再灌注后引发JAK2/STAT3信号通路的激活,抑制该通路的激活起到减少神经元死亡,减轻神经功能缺损等脑保护作用。     

JAK2/STAT3信号转导通路在缺血性脑损伤中作用机制的研究

目的 探讨磷酸化JAK2、磷酸化STAT3蛋白在局灶性脑缺血再灌注损伤后的表达及JAK2-STAT3信号转导通路在缺血性脑损伤中的作用.方法 采用大脑中动脉线栓法制作大鼠局灶性脑缺血再灌注损伤模型,应用Western blotting检测大鼠局灶性脑缺血再灌注损伤后磷酸化JAK2、磷酸化STAT3蛋白表达水平的变化.利用原位缺口末端标记法(TUNEL法)研究神经细胞凋亡的变化.同时应用JAK2特异性抑制剂AG490观察其影响.结果 大鼠局灶性脑缺血再灌注损伤后,再灌注损伤3h P-JAK2、P-STAT3蛋白可见少量表达,12h表达增强,24h达高峰,以后逐渐下降,168h后仍有少量表达.缺血再灌注损伤后凋亡细胞也显著增多,再灌注24～48h达高峰,凋亡细胞的变化与磷酸化JAK2、磷酸化STAT3蛋白表达变化一致.应用JAK2特异性抑制剂AG490不但阻断JAK2的磷酸化、STAT3的酪氨酸磷酸化,而且具有抗细胞凋亡作用.结论 脑缺血再灌注损伤后可引发JAK2、STAT3的活化,JAK2/STAT3信号通路可能参与了脑缺血再灌注损伤机制.     

Rho激酶抑制剂对大鼠脑缺血再灌注后JAK2/STAT3信号传导通路的影响

目的 研究JAK2/STAT3信号通路在脑缺血再灌注损伤后的表达情况,并观察Rho激酶抑制剂Y-27632对其调控作用.方法 建立大鼠脑缺血再灌注模型,应用免疫组织化学染色法检测P-JAK2、P-STAT3在梗死区的表达水平,Tunel法检测神经细胞凋亡数量,观察P-JAK2、p-STAT3表达水平与神经元凋亡的相关性.结果 脑缺血再灌注后P-JAK2以及P-STAT3表达均上调,给予P-JAK2抑制剂以及Y-27632后,P-JAK2、P-STAT3的表达均受到抑制,同时减少了神经元凋亡数量,与模型组比较,差异均有统计学意义（P＜0.05）.结论 脑缺血再灌注后JAK2/STAT3信号通路激活,Y-27632可能通过抑制该通路的激活起到减少神经元凋亡,减轻神经功能缺损等脑保护作用.     

预防性应用阿托伐他汀对SD大鼠局部脑缺血再灌注脑组织Caspase-3表达的影响

目的 探讨预防性应用阿托伐他汀对SD大鼠局灶性脑缺血再灌注损伤是否具有脑保护作用及其可能的机制.方法 72只雄性SD大鼠,按随机化原理分成3组:假手术组(n=24)、缺血再灌注组(简称对照组n=24)、阿托伐他汀组(n=24),各组按缺血2 h再灌注2 h、6 h、24 h、36 h分为4个亚组,每组各6只.结果 各相同再灌注时间点,阿托伐他汀组与对照组比较,缺血区变性、坏死的神经元数量减少,空泡样改变减轻,组织间水肿减轻.阿托伐他汀组较对照组Caspase-3阳性表达细胞数明显减少,再灌注2 h、6 h,2组间比较差别有统计学意义(P＜0.05),再灌注24 h及36 h 2组间比较差别有显著性统计学意义(P＜0.01).结论 预防性应用阿托伐他汀能减轻SD大鼠局灶性脑缺血再灌注损伤,减轻神经细胞变性、坏死及组织水肿,使缺血周边区及海马区Caspase-3表达减少.     

抑制ERK1/2对大鼠弥漫性脑损伤后细胞凋亡的影响

目的 探讨抑制细胞外信号调节激酶1/2（ERK1/2）对大鼠弥漫性脑损伤（DBI）后脑组织细胞凋亡的影响。方法 按随机数字表法将228只成年SD大鼠随机分为假手术组（n=12）、DBI组（n=72）、阻滞剂组（n=72）、对照组（n=72）,后三组按动物处死时间分为30 min、3 h、24 h、48 h、72 h和7 d六个亚组,每亚组12只。参照Mamarou自由落体方法制作重型DBI模型。阻滞剂组损伤后尾静脉注射ERK1/2特异性阻滞剂U0126（0.05 mg/kg）,对照组注射等量溶剂二甲基亚砜。免疫印迹法法检测脑组织磷酸化ERK1/2（pERK1/2）的表达水平,免疫组化法检测Caspase-3表达,流式细胞术检测细胞凋亡率。结果 伤后30 min,脑组织pERK1/2表达水平显著增高（P<0.05）,并持续高水平表达至72 h,伤后7 d与假手术组无统计学差异（P>0.05）。伤后3 h,脑组织Caspase-3表达水平和细胞凋亡率均明显增高,72 h达到高峰,伤后7 d仍明显高于假手术组（P<0.05）。伤后30 min、3 h、24 h、48 h、72 h和7 d,阻滞剂组脑组织Caspase-3表达水平和细胞凋亡率均明显低于DBI组和对照组（P<0.05）,而DBI组和对照组均无统计学差异（P>0.05）。结论 阻滞ERK1/2通路,可显著抑制DBI大鼠脑组织Caspase-3的表达,降低细胞凋亡率。     

17-β雌二醇对大鼠脑缺血再灌注损伤细胞凋亡影响的实验研究

目的观察雌二醇对大鼠脑缺血再灌注损伤脑细胞凋亡的影响。方法72只大鼠随机分为假手术组（n=8）、实验对照组及雌二醇治疗组,后两组又进一步分为3h、6h、12h、24h4个时间点,每时间点8只。线栓法建立大鼠局灶性脑缺血再灌注损伤模型,石蜡切片HE染色及免疫组化染色检测脑组织的细胞凋亡情况及凋亡调控基因Bcl-2、Caspase-3的表达。结果雌二醇治疗组的脑组织缺血半暗带区细胞凋亡较实验对照组明显减少;随着再灌注时间的延长,治疗组半暗带区Bcl一2的表达上调而Caspase-3的表达上调减弱。结论17-β雌二醇具有减少脑缺血再灌注损伤细胞凋亡的作用,而凋亡抑制基因Bcl-2的表达升高及凋亡执行蛋白Caspase-3的表达减弱可能其是重要机制之一。     

JAK/STAT信号转导通路在IGF-1抑制左旋多巴诱导的多巴胺能神经元凋亡中的作用

目的 探讨胰岛素样生长因子1(IGF-1)通过JAK/STAT信号转导通路对左旋多巴诱导的多巴胺能神经元凋亡的保护作用.方法 应用100μg/L β神经生长因子(β-NGF)将体外常规培养的PC12细胞诱导分化为多巴胺能神经元.MTT比色法筛选左旋多巴的神经损伤浓度和IGF-1的神经保护浓度(150μmol/L、100nmol/L),实验分为4组:(1)左旋多巴+IGF-1组;(2)左旋多巴+IGF-1+AG490组,AG490(10 μmol/L)在给予左旋多巴和IGF-1前20 min加人;(3)左旋多巴组;(4)对照组.Western blotting检测4组细胞P-JAK2、P-STAT3蛋白表达,Hoechst33258染色和流式细胞仪分别检测细胞凋亡和凋亡率.结果 Westen blotting法检测显示对照组和左旋多巴组P-JAK2、P-STAT3蛋白表达阴性,而左旋多巴+IGF-1组和左旋多巴+IGF-1+AG490组表达阳性.左旋多巴+IGF.1+AG490组P.JAK2、P.STAT3表达强度低于左旋多巴+IGF.1组,差异有统计学意义(P<0.05):Hoechst33258染色结果显示左旋多巴组细胞核固缩及碎裂最明显,较多凋亡小体形成,而左旋多巴+IGF-1组与左旋多巴+IGF-1+AG490组仅有少量凋亡小体形成.流式细胞仪检测显示4组多巴胺能神经元凋亡率不同,差异有统计学意义(F=180.991,P=0.000);与对照组比较,另3组细胞凋亡率均增高,差异有统计学意义(P<0.05);其中左旋多巴组细胞凋亡率最高,其次为左旋多巴+IGF-1+AG490组、左旋多巴+IGF-1组.结论 大剂量左旋多巴对多巴胺能神经元具有毒性作用.IGF-1对左旋多巴诱导的神经细胞毒性作用呈保护作用,JAK2/STAT3信号转导通路参与了此过程.

Abstract：

Objective To explore the protective effect of insulin-like growth factor 1 (IGF-1) on apoptosis of dopaminergic neurons induced by L-dopa via JAK/STAT signaling pathway. Methods PC12 cells were induced to differentiate into dopaminergic neurons with 100 μg/L β-NGF; MTT assay was employed to identify the changes in the viability of PC12 cells following L-dopa treatment at 0, 10,20, 50, 100, 150 and 200 μmol/L, and the different concentrations of IGF-1 at 0, 10, 25, 50 and 100 nmol/L with the same concentration of L-dopa (150 μmol/L); Western blotting was used to detect the levels of P-JAK2/P-STAT3 in PC12 cells treated with PBS (controls), L-dopa, L-dopa+IGF-1 and L-dopa+IGF-1+AG490 for 24 h, and then the apoptosis rate was assessed by flow cytometry and Hchest33258 staining. Results Western blotting showed that the expressions of P-JAK2 and P-STAT3 were detected in the L-dopa+IGF-1 and L-dopa+IGF-1+AG490 treatment groups but not in the control group or L-dopa treatment group; the expression of P-STAT3 in the L-dopa+IGF-1+AG490 treatment group was obviously lower than that in the L-dopa+IGF-1 treatment group (P<0.05). Hchest33258 staining indicated that L-dopa treatment group had the most obvious karyopyknosis and karyorrhexis,much more apoptotic bodies than the L-dopa+IGF-1 and L-dopa+IGF-1+AG490 treatment groups. Flow cytometry showed that the apoptosis rate was significantly different among the 4 groups (F=180.991,P=0.000): as compared with the control group, the other 3 groups had a higher apoptosis rate (P<0.05);L-dopa treatment group (38.13 ±2.54 %) enjoyed the highest level, followed by L-dopa+IGF-1 +AG490treatment group (25.60±1.30 %) and L-dopa+IGF-1 treatment group (20.17±1.54 %). Conclusion L-dopa has toxic effect on PC12 cells; IGF-1 could protect the PC12 cells from the neurotoxic effect of L-dopa and JAK2/STAT3 signaling pathway is activated in this procedure.     

Mental illness in England,in Scotland and in Scots living in England

Summary Beginning from the observation that Scots living in England have much higher rates of mental hospital admission than do the English, several hypotheses are proposed to account for this. Much of the excess in rates of mental illness is accounted for by those diagnosed as having alcohol-related disorders and behaviour and personality problems. The results of an examination of offical statistics in the two countries enabled some explanations to be offered. It was found that rates of admissions to mental hospitals are higher in Scotland than in England but not as high as those found among Scots migrants who have a much higher rate of readmission to hospitals than either of the other groups. In fact, if first admissions only are considered the rates of admission in Scotland are not only higher than rates for English natives but also higher than for Scottish migrants. It seems that Scots living in England are somewhat less likely to become mental patients than Scots in Scotland but that once they do achieve this status they are very much more likely to be readmitted on subsequent occasions. It was concluded that there might be two fairly distinct groups of migrants from Scotland to England who have different backgrounds, different reasons for migrating and different psychological characteristics. On the one hand there are stable, economically motivated migrants who move south for definite employment related reasons and who show few psychological symptoms. While on the other hand there is a group of migrants who perhaps have psychological problems and who move more in hope than expectation without definite prospects and who account for the high rates of mental hospital admission found in Scottish migrants.     

Prostacyclin release in the coronary circulation during sustained stimulation in in vitro and in in vivo experimental systems

Prostacyclin release from rat isolated perfused hearts and from dog coronary circulation was studied by measuring immunoreactive 6-keto-PGF1 alpha (6-keto-PGF1a) in heart perfusate and in plasma obtained from the great cardiac vein respectively. Continuous infusion of arachidonic acid at constant concentration in isolated perfused hearts induced an increased prostacyclin release. This release showed a rapid peak within 10 min and a subsequent decrease. Low-flow ischemia induced an increased perfusate concentration of 6-keto-PGF1a but, considering the decreased flow, prostacyclin release was actually reduced. During the whole period of ischemia (60 min) prostacyclin release was constant. In open-chest anesthetized dogs 6-keto-PGF1a concentration in the great cardiac vein was increased after ligation of the left anterior descending coronary artery. A prolonged period of coronary occlusion (4.5 hours) resulted in a progressive rise of prostacyclin release. 6-keto-PGF1a determinations in the femoral vein and in the aorta did not show relevant variations during the observation period.     

癫痫与抑郁关系的研究进展

抑郁是癫痫患者中常见的精神障碍,严重地影响了患者的生活质量。传统的观点认为癫痫患者因为存在着诸多社会学问题易出现抑郁倾向,癫痫和抑郁是单向的联系,但大量的研究已经证明癫痫和抑郁之间存在双向的联系,一种异常状态的存在可能易转化为另一种异常状态的发展。癫痫和抑郁存在着共同的发病机制。本文主要就癫痫和抑郁的双向联系以及抗抑郁药物在癫痫患者中的应用进行阐述。     

神经介入：回眸2022

<正>2022年,国际上公布了多项大型神经介入领域的随机对照试验（randomized controlled trial,RCT）结果,在血管内治疗（endovascular treatment,EVT）急性大血管闭塞（large vessel occlusion,LVO）适应证的扩展、药物治疗、管理,症状性颅内动脉粥样硬化性狭窄（symptomatic intracranial atherosclerotic stenosis,sICAS）治疗,无症状性颈动脉狭窄治疗,     

Neuroimaging in epilepsy in tropics

Epilepsy is a major public health problem in many tropical countries. Also, some of the tropical diseases are major contributors to the higher prevalence of epilepsy in these countries. The etiologic factors responsible for epilepsy in these countries are quite different from those in the developed world. This article discusses the etiologic factors and neuroimaging of epilepsy in light of the conditions in these tropical countries.