凉血通瘀方干预高血压大鼠急性脑出血模型对脑组织中差异miRNA表达的影响＊

目的 研究凉血通瘀方对高血压大鼠急性脑出血模型脑组织miRNA表达的影响，对差异表达的miRNA靶基因进行分析，探索凉血通瘀方可能的药效机制。方法 将自发性高血压大鼠随机分成对照组（B）和实验组（C）。适应性饲养一周后，C组灌胃凉血通瘀方，B组灌胃等体积生理盐水，连续5天，每天1次。构建脑出血模型后收集脑组织，借助全转录组测序技术获得miRNA表达量，与miRBase数据库比对获取已知miRNA，使用miRDeep2预测新miRNA。差异分析软件为DESeq2，筛选阈值为|log₂FC| ≥1 并且P <0.05。对显著差异表达的miRNA进行靶基因预测，对靶基因进行GO功能、KEGG通路富集和PPI网络分析。结果 实验组和对照组对比，共发现21个显著差异表达的miRNA，上调有9个，下调有12个，共预测得到1243个有统计学意义的靶基因。GO富集分析发现，生物过程中突触囊泡分泌的调节、神经递质分泌的调节和神经递质运输的调节占前三位，神经元投射终点、全膜、质膜区域和细胞投射则是主要的细胞成分。分子功能分别为小GTPase绑定、底物特异性跨膜转运蛋白活性和离子跨膜转运体活性。通路分析结果显示，靶基因在癌证通路、pI3K-Akt信号通路、人类乳头瘤病毒感染、神经活性配体-受体相互作用和MAPK通路等分布广泛。采用STRING网站和Cytoscape软件，根据MCC算法筛选出ADRA2C、CASR、CCL28、CCR1、DRD2、GNAT3、GRM2、DYNC1LI1、GABBR1、GNAI1等核心靶基因。结论 凉血通瘀方对脑出血急性期鼠脑组织内miRNA的表达有重要影响；显著差异表达miRNAs可能通过靶向核心基因调控凉血通瘀方干预急性脑出血的病理过程及预后。     

颈动脉狭窄支架成形术能替代内膜剥脱术吗?

颈动脉分叉处独特的血流动力学特征决定了该处是动脉粥样硬化最易发生的部位，造成管径的狭窄而导致脑组织远端血流动力学性梗死。另外，沿颈动脉球内侧壁的血流保持层流，有着很高的流速和很强的剪切力，而其外侧壁处血流的分离、停滞、湍流和复杂震荡的剪切力都可引起动脉粥样硬化性斑块的脱落。因此，颈动脉粥样硬化性狭窄是导致卒中发生的主要原因之一（占卒中发生的10％～20％），对其治疗是多年来受全球关注的热点。     

亚低温治疗重型颅脑损伤中脑组织氧分压的临床意义

目的观察亚低温治疗重型颅脑损伤过程中患者颅内压及脑组织氧分压的变化及临床意义。方法将80例急性重型颅脑损伤患者,随机分为亚低温治疗组(40例)和对照组(40例)。亚低温组入院后或术后立即给予亚低温治疗,保持肛温在32~34℃,持续24h~5d;对照组给予常规治疗。两组均观察颅内压(ICP)和脑组织氧分压(PbtO2)变化。结果亚低温组治疗后,ICP明显下降,PbtO2逐渐升高,与对照组相比有显著性差异。结论亚低温治疗能降低脑外伤后增高的ICP,提高PbtO2;伤后24h内持续PbtO2<5mmHg预示患者预后不良。     

一种新型的适用于延迟溶栓治疗的大鼠脑血栓模型的制作

目的 通过对血栓大小的改良,建立适用于延迟溶栓治疗的大鼠脑血栓模型.方法 将10个长度0.8～1.0 mm、宽度0.35 mm的白色血栓经颈内动脉分别注入栓塞脑动脉,形成局灶性脑血栓模型.接受脑血管栓塞的138只SD雄性大鼠被随机分为两大组,分别为单纯缺血组(n=68)和延迟溶栓治疗组(n=70).单纯缺血组不接受任何治疗;延迟溶栓治疗组分别在血栓注入3、6和9 h后,将10 mg/kg的rt-PA自股静脉缓慢注入.使用MRI评价梗死灶的位置、大小、栓塞后不同时间的相对脑血流量.末次MRI检查结束后,大鼠脑组织用4%甲醛固定,作病理检查.结果 共有131只大鼠在血栓注入后脑内形成明确梗死灶,模型成功率为95%,脑梗死仅位于同侧大脑半球占84.7%(111/131),局限于左侧顶叶皮质或(和)左侧基底节的占79.4%(104/131),局灶性脑梗死体积占同侧大脑半球(23.12±6.04)%;对侧大脑半球也同时出现梗死灶占14.5%(19/131).发生局灶性出血11只,大面积出血1只,出血率为9.2%(12/131),均发生在延迟溶栓组.单纯缺血组大鼠,在血栓注入后3、6和9 h的rCBV分别为(34.13±17.55)%、(40.67±25.91)%和(40.72±26.51)%,各组之间rCBV均无显著差异(分别为3 h和6 h,Z=-0.958,P=0.338,3 h比9 h,Z=-1.147,P=0.251).延迟溶栓后成活率高(24 h死亡13只;48 h死亡1只,溶栓后8 d和12 d各死亡1只).结论 改良后的大鼠脑血栓模型是可靠的可重复性的类似于人类大脑中动脉分支栓塞的脑血栓模型,适用于研究延迟溶栓治疗的大鼠脑血栓模型.     

血管性痴呆研究进展

随着世界人口老龄化的发展及脑卒中发病率的升高，血管性痴呆（VD）的发生率亦有所升高，正日益受到人们的重视。近年来，有关VD的研究取得较大进展，本主要对VD的危险因素，分类，诊断和防治等方面的研究简要做一综述。     

预吸氧大鼠脑组织HSP70和MDA的变化

目的 观察预吸氧大鼠脑组织热休克蛋白70(HSP70)和丙二醛(MDA)的变化，以探讨预吸氧对脑损伤的作用。方法 70只Wistar大白鼠随机分为A、B、c三组(7亚组)：A1(正常对照组)、B1-B3(50％预吸氧15、30、60min组)、C1-C3(100％预吸氧15、30、60min组)。按照预吸氧浓度、时间分组实验，取大脑保存，免疫组化分析大脑皮层HSP70阳性神经元变化，硫代巴比妥酸法(TAB)检测脑匀浆液中MDA含量。结果 病理示B1-B3组损伤轻微，C1-C3组神经元损伤严重，与预吸氧时间无关；预吸氧诱氏HSP70产生；C1-C3组随吸氧时间延长MDA水平升高显著。结论 1．预吸氧对神经元有不同程度的损伤作用，50％预吸氧可引起轻微的可逆性损伤，100％预吸氧可引起严重的不可逆性损伤。这种损伤可诱导神经元HSP70的合成，但HSP70不能完全修复神经元的损伤。2．脑损伤程度与MDA变化并不完全一致，预吸氧浓度越高引起的损伤越重。     

浅谈急性一氧化碳中毒的防治

急性一氧化碳中毒系指急性一氧化碳中毒患者，在意识障碍恢复后，经过约2～60天的“假愈期”可出现下列临床表现：①精神意识障碍：痴呆状态，谵妄状态或去大脑皮层状态；②锥体外系神经障碍；③锥体系神经损害；④大脑皮层局灶性功能障碍。文献报道约有10％的急性一氧化碳中毒者经抢救恢复后会患迟发性脑病。病理基础为急性一氧化碳中毒导致脑组织缺血、缺氧、脑循环障碍，可促使血栓形成，神经细胞水肿，变性坏死，甚至继发脑软化或广泛的脱髓鞘病变所致。现就迟发性脑病的防治作一概述。[第一段]     

颅底骨折并发脑脊液漏的观察与护理

颅底骨折多是由于钝性暴力造成，常合并有脑膜、血管、脑组织和颅神经的损伤。并且可能继发颅内感染，脑脊液漏等，较一般颅骨骨折处理起来困难，我科自2001-2004年以来此类患者经过严密的观察护理，无一例并发症发生。均康复出院，现将有关护理介绍如下：     

Influence of moderate hypothermia on cerebral oxygenation in pigs with intracranial hypertension

BACKGROUND: Moderate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxygenation is also one of them. OBJECTIVE: To observe the influence of moderate hypothermia on cerebral oxygenation of animals with acute intracranial hypertension, and further investigate the protective mechanism of moderate hypothermia. DESIGN: A randomized controlled trial. SETTING: Department of Neurosurgery, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University. MATERIALS: Twenty healthy little pigs, either male or female, weighing 4.5–5.5 kg, were used. Neurotrend-typed multiparameter monitoring system (Diametrics Company, British); CMA/100 micro-injection pump (Carnegie Company, Sweden). METHODS: The experiment was conducted in the Changzheng Hospital affiliated to the Second Military Medical University of Chinese PLA in November, 2001. The pigs were randomized into two groups: the normothermia group (control group, n =10) and moderate hypothermia group (n =10). ① Bilateral femoral arteries were separated, one was connected to pressometer for monitoring mean arterial pressure (MEP), and the other for analysis of blood gases [including peripheral blood pH value, arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of carbon dioxide (PaCO2), HCO3–]. ② Rectal temperature was monitored with mercurial thermometer. ③ Intracranial pressure was monitored using Camino optic ICP probe placed in the subdural space. ④ Neurotrend multiparameter monitoring sensor was inserted into the white matter for about 4 cm to determine cerebral perfusion pressure (CPP, CPP=MAP(ICP), brain tissue partial oxygen pressure (PO2), partial pressure of carbon dioxide (PCO2), HCO3– and brain temperature. The rectal temperature of animals in the moderate hypothermia group was lowered to 34 ℃ using ice bags, and the body temperature was maintained at 33–35 ℃ for 2 hours. The changes of the parameters were observed continuously, and the pigs in the normothermia group were not treated with cooling. MAIN OUTCOME MEASURES: ① MAP, ICP, rectal temperature, CCP; Indexes of cerebral oxygenation detected with Neurotrend-typed multiparameter monitoring system; ② Results of blood gases analysis in the moderate hypothermia group. RESULTS: All the 20 pigs were involved in the analysis of results. ① MAP, ICP, rectal temperature, CCP and indexes of cerebral oxygenation: In the moderate hypothermia group, the ICP after cooling was obviously lower than that before cooling [(3.31±1.19), (5.33±0.95) kPa, P < 0.05], CCP was higher, brain tissue PCO2 [(12.03±1.73), (10.59±2.01) kPa, P < 0.05], and brain tissue pH value was higher [(7.03±1.63), (9.40±1.30) kPa, P < 0.05], whereas the brain temperature was decreased as compared with that before cooling [(34.9±0.3), (37.2±0.2) ℃, P < 0.05]. ② Results of blood gases analysis in the moderate hypothermia group: There were no significant differences in the parameters of peripheral arterial blood gases analysis before and after cooling in the moderate hypothermia group (P > 0.05) CONCLUSION: Moderate hypothermia will not impair the cerebral oxygenation, and it can reduce brain tissue CO2 and decrease brain tissue acidosis.