宫内窘迫后胎鼠肾脏细胞间粘附分子-1的表达及意义

目的　缺血缺氧性肾损伤的发生过程有炎症反应参与 ,而这种炎症反应的发生与细胞粘附分子有关 ,其中细胞间粘附分子 1(ICAM 1)可上游调节并介导白细胞与内皮细胞的粘附而致肾损伤。该文旨在探讨宫内急性缺血缺氧及再灌注时ICAM 1在胎鼠肾脏炎症反应发生中的作用。方法　通过钳夹孕 2 1日龄大鼠供应子宫的血管制备胎鼠宫内不同程度缺血缺氧模型和再灌注不同时间模型 ;利用免疫组织化学技术动态观察ICAM 1的变化 ,同时应用HE染色观察病理学改变。结果　ICAM 1在假手术组胎鼠肾组织即有少量表达 ,表达部位主要在近曲小管。比较肾皮质近曲小管ICAM 1的表达情况显示 :宫内缺血缺氧后 ,在 35min和 4 5min表达增强 ,差异有显著性 (P <0 .0 5 )。与假手术组相比 ,宫内缺血缺氧 15min后再灌注 2h ,ICAM 1表达即明显增强 (P <0 .0 1) ,15h达高峰 ,再灌注 30h时表达仍强于假手术组 (P <0 .0 5 )。病理学改变 :缺血 15min再灌注 15h病理改变最明显 ,肾组织普遍充血和渗出 ,可见中性粒细胞浸润 ,肾小管普遍空泡变性 ,伴细胞核模糊 ,细胞崩解 ,基底膜阶段性断裂 ,尤以近曲小管明显。结论　宫内急性缺血和再灌注后胎肾存在炎症反应 ;宫内急性缺血缺氧可以导致ICAM 1表达增强 ,其表达变化与病理学改变一致 ,提示ICAM 1     

胎鼠急性缺血／再灌注损伤肾NO和NOS的改变

研究宫内急性缺血缺氧及再灌注时胎鼠肾NO水平及NOS活性变化，以无创动脉夹钳夹孕鼠供应子宫和卵巢的动静脉血管，制成宫内急性缺血缺氧及再灌注模型，以硝酸还原酶法和免疫组化法测定胎鼠肾NO水平和NOS活性变化。结果：显示随缺血缺氧时间延长NO水平明显降低，与假手术组相比，差异显著P＜0．01。随再灌注时间延长NO水平呈双向改变，尤为缺血缺氧30分钟组，正常时eNOS和iNOS即位于近曲小管，随缺血缺氧及再灌注时间的延长，eNOS光强度逐渐升高，iNOS光强度逐渐显著减弱，尤为缺血缺氧30分钟再灌注组，表明NO的动态变化可能参与缺血缺氧再灌注损伤过程，缺血缺氧及再灌注后肾NO水平的双相改变可能是eNOS和iNOS活性变化的综合结果。     

宫内急性缺血缺氧后胎鼠肾脏钙离子腺苷三磷酸酶动态变化的研究

目的：研究宫内急性缺血缺氧后(HI)胎鼠肾脏钙离子腺苷三磷酸酶(Ca2+-ATPase)的动态变化,探索围产期窒息后肾损伤发生细胞内钙超载的机制。方法：通过钳夹孕21 d大鼠供应子宫的动静脉血管,制成胎鼠宫内不同程度HI模型和HI后再灌注不同时间模型。采用化学方法测定胎鼠肾脏细胞膜和线粒体Ca2+-ATPase的活性变化。结果：假手术组胎肾细胞膜和线粒体Ca2+-ATPase活性分别为(7.476±0.353)和(3.470±0.270) 微摩尔磷/毫克蛋白·小时(μmol.Pi/mgprot.h),宫内HI 15 min后Ca2+-ATPase活性均明显减弱,分别为(6.411±0.210)和(2.886±0.245) μmol.Pi/mgprot.h,(P0.05),但线粒体Ca2+-ATPase活性(3.234±0.143) μmol.Pi/mgprot.h,仍低于假手术组(P<0.05)。结论：宫内HI后胎肾Ca2+-ATPase活性的降低是发生细胞内钙超载导致肾损伤的重要机制。     

宫内急性缺血缺氧后胎鼠肾脏细胞间粘附分子—1表达的研究

为探讨宫内急性缺血缺氧及再灌注时细胞间粘附分子 1(ICAM 1)在胎鼠肾脏损伤发生中的作用 ,通过钳夹孕 2 1日龄大鼠供应子宫的动静脉血管以制备胎鼠宫内不同程度缺血缺氧模型和再灌注不同时间模型 ;利用逆转录聚合酶链式反应动态观察ICAM 1mRNA的变化。结果显示 :正常时ICAM 1mRNA在 2 1日龄胎鼠肾脏有一定表达。宫内缺血后 ,胎肾ICAM 1mRNA在缺血 35分钟时开始表达增强 (P <0 0 5 ) ,4 5分钟时达高峰 (P <0 0 1)。缺血 15分钟再灌注过程中 ,胎肾ICAM 1mRNA在再灌注 1小时时即开始表达增强 (P <0 0 5 ) ,8和 15小时时为表达高峰 ,明显强于其它各时间点 (P <0 0 5 ) ,此后表达下降 ,在 30小时已接近假手术组水平 (P >0 0 5 )。因此 ,可以认为宫内缺血缺氧可以刺激胎鼠肾脏ICAM 1mRNA的转录 ,提示ICAM 1可能和窒息后肾损伤发病关系密切。     

宫内窘迫胎鼠肾组织环氧化酶-2表达的实验研究(英文)

目的　缺血缺氧性肾损伤是一个复杂的病理生理过程,炎症反应在其中占有重要的作用。该文 旨在观察宫内窘迫后胎鼠肾组织炎症介质环氧化酶 2(COX 2)蛋白和基因表达及其代谢产物前列环素I2(PGI2), 前列腺素E2(PGE2)和血栓素(TXA2)的动态变化,初步探讨COX 2在宫内窘迫胎鼠肾损伤发病机制中的作用。方 法　制备胎鼠宫内缺血缺氧再灌注模型(缺血缺氧组:缺血缺氧30min;再灌注组:缺血缺氧30min后,分别再灌注 0.5h,2h,6h,12h,24hand30h)。各时间点分别取胎鼠20只,假手术组胎鼠22只,将肾组织匀浆后采用 RT PCR,Western印迹杂交和放免法进行检测。同时苏木精 伊红染色观察肾组织病理学改变。结果　宫内窘迫 后胎肾组织COX 2蛋白和基因表达上调,PGI2的稳定代谢产物6 keto PGF1α及PGE2均于再灌注2h开始增高(P <0.05)。其中6 keto PGF1α增加迅速,于再灌注12h达高峰(P<0.01),PGE2于再灌注24h达最高水平(P< 0.01),而TXB2增加幅度不大。结论　宫内缺血再灌注从转录水平诱导胎肾COX 2蛋白表达增强,COX 2的主要 代谢产物是PGI2和PGE2。COX 2可能通过PGI2和PGE2对缺血性胎肾损伤具有保护作用,因此,在围产期肾损 伤不宜应用COX 2抑制剂。     

胎鼠急性缺血/再灌注损伤肾NO及NOS的改变

研究宫内急性缺血缺氧及再灌注时胎鼠肾NO水平及NOS活性变化,以无创动脉夹钳夹孕鼠供应子宫和卵巢的动静脉血管,制成宫内急性缺血缺氧及再灌注模型.以硝酸还原酶法和免疫组化法测定胎鼠肾NO水平和NOS活性变化.结果显示随缺血缺氧时间延长NO水平明显降低,与假手术组相比,差异显著P＜0.01.随再灌注时间延长NO水平呈双向改变,尤为缺血缺氧30分钟组.正常时eNOS和iNOS即位于近曲小管.随缺血缺氧及再灌注时间的延长,eNOS光强度逐渐升高,iN-OS光强度逐渐显著减弱,尤为缺血缺氧30分钟再灌注组.表明NO的动态变化可能参与缺血缺氧再灌注损伤过程.缺血缺氧及再灌注后肾NO水平的双相改变可能是eNOS和iNOS活性变化的综合结果.     

病毒性脑炎患儿一氧化氮和肿瘤坏死因子α的变化

目的 探讨病毒性脑炎（病脑）患儿血清和脑脊液一氧化氮（NO）和肿瘤坏死因子α（TNF－α）的变化。方法 应用ELISA等方法测定34例病脑患儿的血清和脑脊兴中NO和TNF－α的水平。结果 病服患儿血清NO和TNF－α水平较对照组明显升高（P＜0．01），昏迷患者比较症更高（P＜0．01），NO和TNF－α与病情严重程度呈正相关。脑脊液NO和TNF－α急性期恢复期有明显增同。结论 提示血清NO和TNF－α的水平与病脑的发生发展和病情严重程度有关。     

肠缺血再灌注时肿瘤坏死因子免疫组织化学研究

目的　探讨肠缺血 /再灌注时肿瘤坏死因子 (tumornecrosisfactorα,TNF α)的来源及作用。方法　① 4 8只雄性Wistar大白鼠体重 (130± 15 ) g ,分成 6组 (n =8) ,假手术组 ,缺血 30min组 ;缺血 30min ,再灌注组 ;缺血 30min ,再灌注 6 0min组 ;缺血 30min ,再灌注 90min组 ;缺血 12 0min组 ;②利用免疫组织化学技术检测肠、肝组织TNF α蛋白表达和分布。③对肠组织进行HE染色。结果　①肠粘膜免疫组化于缺血 130组 ;缺血 30min ,再灌注 6 0min组 ;缺血 30min ,再灌注 90min组时可见TNF α强阳性物质 ,缺血 30min ,再灌注 90min组 ;可见极强阳性物质 ;②缺血 30min ,再灌注 30min组 ;缺血 30min ,再灌注 6 0min组肝组织内可见阳性物质 ,缺血 30min ,再灌注 90min组 ;为强阳性物质 ;③肠组织HE染色显示I30’G肠粘膜轻度受损 ,缺血 30min ,用灌注 30min组 ;缺血 30min ,再灌注 6 0min组 ;缺血 30min ,再灌注 90min组肠粘膜中度受损 ,再灌注 12 0min组肠粘膜重度受损。结论　幼鼠肠缺血 /再灌注后TNF α在肠、肝内均有阳性反应 ,但肠粘膜内TNF α较肝内明显 ,因此推论幼鼠肠缺血 /再灌注损伤早期TNF α可能主要来源于肠组织 ,并且介导幼鼠肠缺血 /再灌注损伤的病理过程     

缺氧诱导因子-1α在缺氧缺血皮质神经元中的表达

目的探讨缺氧诱导因子-1α（HIF-1α）蛋白及其mRNA在体外培养大鼠皮质神经元缺氧和（或）缺血过程中的表达情况。方法培养16~18 d胎鼠皮质神经元,建立体外神经元缺氧缺血（HI）、单纯缺氧、单纯缺血模型。在缺氧和（或）缺血再灌注后不同时间点,采取免疫细胞化学、原位杂交技术检测皮质神经元HIF-1α蛋白及其mRNA的表达。结果常氧下神经元HIF-1α蛋白有微弱表达,在缺氧和（或）缺血处理后,其表达明显增高,HI再灌注4~8 h后HIF-1α蛋白表达最高,与其他时间点比较均有显著差异（Pa=0）,12 h后开始下降;且HI组HIF-1α蛋白较单纯缺氧和单纯缺血组表达高,差异有统计学意义（Pa=0）。HIF-1αmRNA表达在HI后即达到高峰,2 h后渐下降,在8 h呈低水平表达。结论HIF-1α在缺氧和（或）缺血后的皮质神经元表达的差异具有一定时间规律性,提示对HI神经元进行HIF-1α基因治疗可能是一种可行的方法。     

促肝细胞生长素对大鼠肾缺血再灌注损伤细胞凋亡的干预

目的探讨促肝细胞生长素（pHGF）对肾缺血再灌注损伤（IRI）大鼠肾功能及‘肾小管上皮细胞凋亡的影响。方法雄性Sprague—Dawley大鼠32只，随机分为假手术组（组I）、缺血再灌注组（组Ⅱ）、缺血再灌注前pHGF干预组（组Ⅲ）和缺血再灌注后pHGF干预组（组Ⅳ）。采用无损伤动脉夹钳夹大鼠双侧肾蒂45min，制作肾IRI模型。组I和组Ⅱ腹腔注射等量9g／L盐水（0．8mL），组Ⅲ和组Ⅳ分别在术前和术后腹腔注射pHGF 50mg／kg。于IRI 12 h股动脉采血，处死动物后迅速摘取其左侧肾脏。采用酶法检测血清肌酐（Scr），采用肾组织原位细胞凋亡标记法（TUNEL）检测肾小管上皮细胞凋亡。结果组Ⅱ血清Scr水平（120．850&#177;22．237）μmol／L明显高于组I（22．775&#177;6．508）μmol／L（P〈0．01），组Ⅲ（60．413&#177;10．197）μmol／L和组Ⅳ（69．40&#177;11．443）μmol／L表达水平均明显较组Ⅱ下降（Pa〈0．01）。组Ⅱ肾脏凋亡阳性细胞的表达（26．850&#177;1．476）较组I（0．90&#177;0．385）明显升高（P〈0．01），组Ⅲ（8．30&#177;1．146）和组Ⅳ（9．0&#177;0．869）均较组Ⅱ显著下调（Pa〈0．01）。组Ⅲ和组Ⅳ间各项值比较差异均无显著性差异（Pa〉0．05）。结论pHGF能显著降低肾缺血再灌注损伤大鼠血清Scr水平，显著抑制其肾小管上皮细胞凋亡，对缺血性急性肾衰竭既有保护又有治疗作用。     

实验性新生儿缺氧缺血脑损伤模型鼠脑细胞凋亡动态变化

目的 探讨新生儿缺氧缺血脑损伤（ＨＩＥ）后皮质、海马细胞凋亡现象和动态过程。方法 制作标准化ＨＩＥ实验模型,应用ＤＮＡ原位末端标记（ＴＵＮＥＬ）、ＨＥ染色、电镜方法,对凋亡出现时间和强度进行观察和比较。结果 缺氧缺血后新生鼠脑细胞死亡具有典型凋亡特征,光镜、电镜观察到核膜皱缩、染色质凝聚,阳性ＴＵＮＥＬ着色细胞核。随着缺血时间的增加,细胞凋亡数逐渐增加,皮质约在１８小时点、海马４０小时点达高峰。结     

黄体酮对缺氧小鼠脑损伤的影响

目的观察小鼠缺氧后脑组织水、钾、钠含量的变化,探讨黄体酮(PROG)在脑缺氧中的神经保护作用。方法32只雄性小鼠随机分为正常对照组、单纯缺氧组、低PROG组和高PROG组,后两组于缺氧前30min腹腔注射.PROG4mg/kg或8mg/kg。小鼠缺氧24h断头取脑.测脑组织的水、钾、钠含量。结果缺氧24h后,缺氧组脑组织水、钾、钠含量均明显高于正常对照组(P<0.01)。经PROG预处理的两组与单纯缺氧组相比,脑组织水、钾、钠含量均有所下降,低PROG(4mg/k)组的疗效尤为明显.水下降4.95%(P<0.01),钾下降24.6%(P<0.01).钠下降17.6%(P<0.01);高PROG(8mg/kg)组水含量下降有显著差异(P<0.01),但钾、钠下降不显著(P>0.05)。结论小鼠缺氧24h后脑组织水、钾、钠含量明显升高.PROG可抑制缺氧脑内水、钾、钠的升高,产生一定的神经保护作用。     

Frequency of sub-clinical cerebral edema in children with diabetic ketoacidosis

Symptomatic cerebral edema occurs in approximately 1% of children with diabetic ketoacidosis (DKA). However, asymptomatic or subclinical cerebral edema is thought to occur more frequently. Some small studies have found narrowing of the cerebral ventricles indicating cerebral edema in most or all children with DKA, but other studies have not detected narrowing in ventricle size. In this study, we measured the intercaudate width of the frontal horns of the lateral ventricles using magnetic resonance imaging (MRI) in children with DKA during treatment and after recovery from the DKA episode. We determined the frequency of ventricular narrowing and compared clinical and biochemical data for children with and without ventricular narrowing. Forty-one children completed the study protocol. The lateral ventricles were significantly smaller during DKA treatment (mean width, 9.3 +/- 0.3 vs. 10.2 +/- 0.3 mm after recovery from DKA, p < 0.001). Children with ventricular narrowing during DKA treatment (22 children, 54%) were more likely to have mental status abnormalities than those without narrowing [12/22 vs. 4/19 with Glasgow Coma Scale (GCS) scores below 15 during therapy, p = 0.03]. Multiple logistic regression analysis revealed that a lower initial PCO2 level was significantly associated with ventricular narrowing [odds ratio (OR) = 0.88, 95% confidence interval (95% CI) = 0.78-0.99, p = 0.047). No other variables analyzed were associated with ventricular narrowing in the multivariate analysis. We conclude that narrowing of the lateral ventricles is evident in just over half of children being treated for DKA. Although children with ventricular narrowing did not exhibit neurological abnormalities sufficient for a diagnosis of 'symptomatic cerebral edema', mild mental status abnormalities occurred frequently, suggesting that clinical evidence of cerebral edema in children with DKA may be more common than previously reported.     

Giant cerebral arterial aneurysm in an infant: Report of a case and review of 42 previous cases in infants with cerebral arterial aneurysm

A giant cerebral aneurysm with subarachnoidal hemorrhage in a 4-month-old female infant is reported. The clinical course was complicated by an electrolyte imbalance and unexpected intoxication by phenobarbital. She died as a result of the third episode of rerupture of the aneurysm on the 16th day after onset. Histological findings showed that the aneurysm was of the saccular type, 35 × 20 × 22 mm in size, arising from the basilar artery. The aneurysmal wall consisted microscopically of fibrous tissue with partial absence or fragmentation of the internal elastic lamina and muscular lamina. Forty-three cases of cerebral aneurysms during the first year of life including the present case were summarized and it was found that they could be characterized as follows: (i) a high incidence of onset in early infancy; (ii) larger than 10 mm; (iii) a large number arose from the posterior circulation of the circle of Willis; and (iv) a poor prognosis of non-operated groups, especially in the posterior circulation.     

Cerebral Oedema Complicating Diabetic Ketoacidosis

ABSTRACT. Signs of raised intracranial pressure (ICP) developed during treatment of diabetic ketoacidosis in a young child. A CT scan revealed cerebral oedema and direct measurement conlirmed elevated ICP. Aggressive treatment was successful in maintaining cerebral perfusion pressure. The child survived with mild handicap in contrast to the poor outcome of previous reports.     

新生儿缺氧缺血性脑病脑血流动力学变化与血浆内皮素-1、一氧化氮的关系

目的　探讨一氧化氮 (NO)、内皮素 1 (ET 1 )在新生儿缺氧缺血性脑病 (HIE)脑血流动力学变化中的作用。方法　HIE各组均在生后 48～ 72h采用经颅多谱勒超声 (TCD)检测双侧大脑前、中、后动脉收缩峰流速 (Vs)、舒张末期流速 (Vd)、搏动指数 (PI)和阻力指数 (RI) ,同时用硝酸还原酶法和放射免疫法分别测定血浆NO和ET 1水平。对照组同期进行上述检测。结果　 1 .脑血流于轻度组Vd、Vs局部降低 ;中、重度组Vd广泛降低 ,Vs呈局部降低 ,重度组尤为显著 (P均 <0 .0 5)。 2 .PI、RI轻度组与对照组无显著性差异 ;中度组局部增高 ;重度组双侧大脑动脉PI、RI普遍增高 (P均 <0 .0 5)。 3 .HIE各组NO、ET 1水平均高于对照组 ,且与病变程度成正比。但NO/ET 1比值低于对照组 (P均 <0 .0 1 ) ,且重度组 <中度组 <轻度组。结论　HIE患儿脑血流灌注减少与NO、ET 1过量合成、功能失调有关。     

Prothrombotic risk factors in children with hemiplegic cerebral palsy

BACKGROUND: The purpose of the present paper was to investigate the prevalence of prothrombotic risk factors associated with hemiplegic cerebral palsy (CP). METHODS: Twenty-three hemiplegic CP patients were tested for inherited and acquired prothrombotic risk factors, except methylene tetrahydrofolate reductase (MTFR) polymorphism. RESULTS: A total of 56.5% of patients had at least one coagulation abnormality and 13% of them had two. Four patients (8.7%) had infection and congenital heart disease, who also had additional coagulopathy risk factors. Obstetric problems were detected in 56.5%. Coagulopathy risk factors were factor V Leiden mutation (21.7%), protein C deficiency (21.7%), elevated lipoprotein-a (13%), G20210A mutation of prothrombin (8.7%), and protein S deficiency (4.3%). CONCLUSION: Children with hemiplegic CP need to be evaluated for coagulopathic abnormalities.     

Bid基因在新生大鼠缺氧缺血性脑损伤中的动态变化

目的　探讨Bid基因在新生大鼠缺氧缺血性脑损伤 (HIBD)中的动态变化。方法　通过建立新生大鼠HIBD动物模型 ,采用RT PCR技术检测缺氧缺血后不同时间点缺血侧脑组织中Bid基因表达的变化。结果　正常组中无Bid基因表达 ,缺氧缺血组Bid基因表达明显上调 ,且随着缺氧缺血后时间的延长 ,Bid基因表达呈动态变化缺氧缺血后 6h其表达开始增加 ,2 4h达高峰 ,48～ 72h有所回落。结论　脑缺氧缺血引起的神经细胞凋亡可能与Bid基因表达上调有关。     

Intellectual Impairment with Regional Cerebral Dysfunction after Low Neonatal Cerebral Blood Flow

Lou, H. C., Skov, H. and Henriksen, L. (Department of Neuropaediatrics, J. F. Kennedy Institute, Glostrup, and Departments of Paediatrics and Neurology, Rigshospitalet, Copenhagen, Denmark). Intellectual impairment with regional cerebral dysfunction after low neonatal cerebral blood flow. Acta Paediatr Scand Suppl 360: 72, 1989.
12 children, in whom neonatal CBF had been measured, were examined at the age of 9 to 10 years by means of clinical neurological examination, neuropsychologic tests and observations, and ¹³³Xe single photon emission computed tomography (SPECT). Performance on most neuropsychologic tests or observations correlated with neonatal CBF but only rarely with other neonatal parameters (birthweight, gestational age, Apgar score at 5 min). Poor performance on each test or observation was in most instances correlated with a distinct pattern of regional cerebral dysfunction as assessed by SPECT. The dysfunctional region tended to be located periventri-cularly and in the watershed regions between major cerebral arteries. It is concluded that low neonatal cerebral perfusion may be an indicator, and possibly a determinant, of later intellectual dysfunction in stressed neonates, and that specific neuropsychologic deficits are associated with specific patterns of cerebral dysfunction in the present patient group.