高浓度氧对沙土鼠脑缺血再灌流后脂质过氧化作用的影响

沙土鼠双侧颈总动脉结扎1小时后,于高氧环境中再灌流2小时,脑MDA含量(4.39±0.26nmol/mg蛋白)与空气对照组(2.63±0.50nmol/mg蛋白)、高氧对照组(3.07±0.52nmol/mg蛋白)、缺血组(2.96±0.41nmol/mg蛋白)及空气中再灌流组(2.79±0.59nmol/mg蛋白)相比较,差异均具有高度显著性(P<0.01)。大脑皮层TXB_2含量增加,6-Keto-PGF_(1α)含量减少,水、钠含量明显增加。但上述各指标与缺血后在大气环境中再灌流组相比,差异均无显著性。作者推测,高浓度氧导致脂质过氧化作用增强的机理可能源于异常的线粒体电子传递链功能。     

神经肽—Y在蛛网膜下腔出血引起脑血管痉挛中的作用

本实验采用大鼠经额向基底池Willis环处插管注入NPY,NE和5-HT,以γCBF变化为指标,观察它们对脑血管的在体效应。实验发现NPY对脑血管具有很强的收缩作用,以克分子浓度计算NPY引起脑血管收缩比5-HT强10倍,比NE强500倍,并可增加NE,5-HT的缩血管效应。人及大鼠CSF中NPY测定发现:SAH伴有CVS的病人,CSF中NPY达291.1±58pg/ml,与对照组(164±28.00pg/ml)相比,P<0.01;大鼠SAH后CSF中NPY含量从2.1±2.1增至6.0±3.2ng/ml(P<0.01),同时大鼠皮层内NPY含量从9.5±0.8下降至4.8±0.8ng/ml(P<0.01),提示脑神经元分泌的NPY参与了CVS过程,并在维持CVS持续状态方面起重要作用。实验还提示SAH病人CSF中NPY含量变化可以作为观察CVS是否出现的指标。     

结扎家兔颈总动脉和颈内动脉前后血浆TXB_2及6-Keto-PGF_(1α)含量的变化

本文报告了用放射免疫法测定家兔血浆中TXB_2及6-Keto-PGF_(1α)的结果。并对外周耳缘静脉及颈内静脉不同部位采血测定结果进行了对比。结果表明,结扎动脉30分钟后造成腑缺血,血浆TXB_2含量明显高于对照组(P<0.01);由颈内静脉采血组测得值,明显高于外用耳缘静脉采血组(P<0.01)。脑缺血组,血浆6-Keto-PGF_(1α)含量,明显低于对照组(P<0.01);由颈内静脉采血组其含量明显低于外周耳缘静脉采血组(P<0.01)。由于闭塞动物颈部大动脉所致的脑缺血,血浆TXB_2/6-Keto-PGF_(1α)比值明显高于对照组。     

血栓素A_2和前列腺环素与自发性高血压大鼠高血压发展的关系

本文观察了SHR和WKY及不同年龄SHR动脉血浆中TXA_2和PGI_2的稳定代谢产物TXB_2和6-Keto-PGF_(1α)的浓度及其比值变化。结果表明,SHR血浆中的TXB_2浓度显著高于WKY,对照组与实验组相比(207.1±59.8比1217.9±298.5P8/ml,P<0.001),而血浆中6-Keto-PGF_(1α)浓度,除高年龄组SHR外,其他各组均无明显改变;SHR各组血浆中6-Keto/TXB_2比值均显著低于WKY组,不同年龄组SHR血浆中TXB_2浓度相比,高年龄组明显高于低年龄组(2184.5±273.1比1290.6±284.4pg/ml,P<0.001),高年龄组血浆中6-Keto-PGF_(1α)浓度虽有升高,但6-Keto/TXB_2比值仍明显低于对照组(0.21±0.12比1.48±0.78,P<0.001)。这些变化可能与SHR高血压的持续发展有关。     

兴奋性氨基酸Ca~(2 )在短暂性脑缺血后海马DND发生机制中的作用

本实验用氨基酸自动分析技术测定脑缺血10分钟时背侧海马氨基酸含量;通过结扎沙土鼠双侧颈总动脉10分钟再灌流7天,造成海马迟发性神经元坏死(delayed neuronal death;DND)模型,以计数海马CA_1区神经元密度作为指标,观察谷氨酸钠和氯胺酮对海马DND的影响;检测背侧海马组织Ca~(2 )含量,观察氯胺酮对背侧海马Ca~(2 )含量的影响。结果表明短暂性脑缺血时谷氨酸和天门冬氨酸含量显著增加(P<0.05);谷氨酸钠能显著降低海马CA_1区神经元密度(P<0.01);氯胺酮能显著提高海马CA_1区神经元密度(P<0.01);再灌流2天后背侧海马组织Ca~(2 )增加(P<0.05),氯胺酮能阻止其增加(P>0.05)。本实验结果均直接或间接提示兴奋性氨基酸和Ca~(2 )在短暂性脑缺血后海马DND发生机制中起着重要作用,Ca~(2 )超载是神经元坏死的最后共同通路。     

山莨菪硷对家兔不完全性脑缺血的影响

急性结扎兔双侧颈总动脉及左侧椎动脉造成了实验性不完全脑缺血模型。此模型可用于探讨缺血性脑病的发病机制及实验治疗。于脑缺血后30及60分钟分别注入654-2(山莨菪硷),可见:(1)654-2治疗组脑血流量下降率明显低于空白对照组(P<0.01)及生理盐水组(P<0.01)。(2)血浆中TXB_2含量明显低于空白对照组(P<0.01)及盐水组(P<0.01)。表明山莨菪硷可以改善局部脑循环和抑制血浆中TXB_2的形成、大脑皮层无明显脑水肿发生。本实验结果提示664-2可用于脑卒中急性期。     

亚低温联合尼莫地平对兔全脑缺血再灌注损伤的保护

目的 探讨亚低温及尼莫地平对脑缺血再灌注损伤的保护作用及机制.方法 健康新西兰大耳白兔24只,随机分为健康对照组(Ⅰ组)、常温缺血再灌注损伤组(Ⅱ组)、亚低温缺血再灌注损伤组(Ⅲ组)、亚低温+尼萸地平组(Ⅳ组),每组6只.采用双侧颈总动脉夹闭低血压脑缺血模型,除健康对照组外,各组均行脑缺血30 min,再灌注3 h;Ⅲ组在双侧颈总动脉夹闭的同时行局部脑组织亚低温处理,Ⅳ组在夹闭的同时行局部脑组织亚低温+尼萸地平10μg·kg-1·h-1静脉输注并维持至再灌注后3 h.常规监测鼓膜温度、创伤性平均动脉压(MAP)和中心静脉压(CVP).分别于缺血前、缺血30 min、再灌注30、60、120、180 min采血标本,血气分析仪检测颈静脉血氧饱和度(SjvO2).再灌注3 h后处死动物,取脑称干湿重比计算脑含水量.ELISA方法检测血清烯醇化酶(NSE)含量.结果 脑含水量Ⅱ组>Ⅲ组>Ⅳ组.Ⅱ组全脑缺血冉灌注后60 min,血清NSE含量明显升高至(14.07±0.67)μg/L,120 min达高峰(18.53±0.85)μg/L,而SjvO2降低至(66±7.6)%.Ⅲ组冉灌注60min时血清NSE含量下降至(7.27±0.25)μg/L;180 min时至(9.17±0.57)μg/L,SjvO2升高至(91±4.5)%,与Ⅱ组比较差异有统计学意义(P均<0.01).Ⅳ组的血清NSE含量显著低于Ⅲ组,差异具有统计学意义.再灌注30 min,颈静脉血氧饱和度升高,Ⅲ组与Ⅳ组差异无统计学意义(P>0.05).结论 局部脑组织亚低温联合尼莫地平静脉输注能显著减少兔全脑缺血再灌注后血清NSE表达,升高SjvO2,减轻缺血再灌注损伤所致的脑水肿.     

芪丹通脉片对缺血/再灌注犬心肌微血管功能的影响

目的评价中药复方芪丹通脉片对急性缺血再灌注致心肌微血管功能的影响。方法应用12只健康犬,随机分为对照组(control)和芪丹通脉片治疗组(QDTMT treatment group),对照组经十二指肠给予生理盐水(1.5ml/kg),给药后30min分离冠状动脉左前降支,放置电磁流量计探头测定血流量,在其下缘左前降支1/2处结扎90min,松开后再灌注180min观察,分别于灌胃前、缺血90min和再灌注180min静脉快速均匀推入微泡声学造影剂SONOVUE,FLASH模式进行静脉声学造影,实时连续记录心肌声学造影前后的图像采用,采用Echopac图象工作站软件包进行分析心肌声学造影的图像视频密度,根据时间-视频密度曲线计算曲线下面积(area under curve,AUC)以评价心肌微血管的血流灌注状态,根据图像分析缺血心肌范围的影响。芪丹通脉片组则经十二指肠给予芪丹通脉片浸膏混悬液(1g/ml,1.5ml/kg),其余实验过程同对照组。并在不同时间点从冠状静脉窦采血,检测血清中NO和血浆中ET-1的含量。结果在基础状态、缺血前和缺血90min,对照组和芪丹通脉片干预组的时间-视频密度曲线计算曲线下面积(AUC)以及缺血后出现的灌注缺损所占左心室的百分比没有显著差异。然而再灌注180min两组的AUC存在显著差异(14.09±2.31 vs 11.47±1.55,P<0.05),左心室心肌灌流均没有完全恢复,但芪丹通脉片能够显著促进再灌注后心肌微循环灌流的恢复(92.10±2.2)%,与对照组(87.49±4.12)%比较,存在显著差异(P<0.05)。在缺血90min和再灌注180min,芪丹通脉片处理组血清中NO和血浆中ET-1分别为(68.98±10.01)μmol/L、(67.55±9.81)μmol/L和(114.73±11.89)μg/L,(139.97±12.36)μg/L,与对照组存在显著差异(56.38±8.27)μmol/L,(53.55±6.03)μmol/L和(137.40±13.48)μg/L,(161.90±19.14)μg/L,(P<0.05)。结论芪丹通脉片能够促进心肌缺血/再灌注后微循环血流的恢复,调节循环血中的NO和ET含量,改善微循环功能,抑制缺血/再灌注所致的心肌损伤。     

缓激肽对大鼠缺血区血脑屏障的影响

目的研究缓激肽对局部脑缺血区超微结构、血脑屏障的通透性及继发性脑水肿的影响。方法制备大鼠大脑中动脉缺血模型,在大脑中动脉缺血2hr再灌注1hr末,颈内动脉灌注小剂量缓激肽(10μg/kg/min),应用电镜观察血脑屏障超微结构的改变;测定脑组织伊文思蓝含量来判断血脑屏障的通透性;应用干湿法测定脑含水量的变化。结果缓激肽灌注大鼠脑毛细血管紧密连接开放,对照组大鼠紧密连接完整;与对照组相比,缓激肽灌注组缺血侧脑组织伊文思蓝含量明显高于缺血对照组(P<0.01),但再灌注24hr后脑含水量并没有增加(P>0.05)。结论小剂量缓激肽通过开放紧密连接来增加缺血区血脑屏障的通透性,但并不会增加继发性脑水肿的程度。     

妊娠高血压疾病与偶联因子、前列环素的相关性研究

目的通过对不同程度、不同孕周妊娠高血压疾病患者、正常孕妇血管内皮细胞活性物质—偶联因子6(CF6)、前列环素I2(PGI2)的检测,探讨其与妊娠高血压疾病发病的相关性。方法选择妊娠高血压疾病患者36例作为研究组,再选同期与之孕周、年龄相匹配的正常孕妇33例作为对照组,采用放射免疫方法检测CF6、PGI2的血浆含量。结果研究组CF6水平明显高于对照组,分别为491.5±95.3(pg/ml);255.3±75.5(pg/ml),两组比较,P<0.01,有极显著性差异;研究组PGI2水平低于对照组,分别为133.5±76.7pg/ml;216.6±89.1(pg/ml),P<0.05,有显著性差异。研究组平均动脉压(MAP)、产时出血量多于对照组,而新生儿体重、Apgar评分均低于对照组,P<0.01,有显著性差异。结论CF6、PGI2两种血管活性物质的失调可能在妊娠高血压疾病的形成过程产生重要的作用。     

Economical and rational in vivo and in vitro diagnosis in Basedow hyperthyroidism

Immunogenic hyperthyroidism (Graves' disease) is a life-long ailment. A widespread diagnostic evaluation is essential for unbiased initial values prior to therapy. The major goals of initial investigation are to determine a functional disturbance of the organ, its pathogenesis and morphology. Even a suppressed ultrasensitive bTSH value represents no evidence of overt hyperthyroidism; a positive diagnosis can only be established by the additional presence of increased parameters of circulating free thyroid hormones (fT3, fT4). Evidence of any immunogenic pathogenesis is given by positive thyroid antibody values (TRAK, MAK, TAK). Moreover, the use of sonography (with poor diffuse echo and increased thyroid depth) as well as Tc-99m scan indicating primary autonomy, thyroxine induced hyperthyroidism or painless thyroiditis) may both prove rather useful in a rational and economical diagnosis of Graves' disease.     

The cyclic-AMP concentration in plasma and in muscle in response to exercise and beta-blockade in man

At rest the cAMP concentration in (muscle samples of) the quadriceps femoris ranged from 1.55 to 3.00 μmol per kg dry muscle and in plasma from 15.3 to 32.3 nmol per 1. Blockade of the beta adrenoreceptors with propranolol resulted in a significant decrease in the concentration in muscle at rest, the magnitude of the fall being related to the inital level. Similarly in plasma there was a trend towards lower levels of cAMP in those with the highest pretreatment levels, but the overall change was not statistically significant. There was no relation between the concentrations in muscle and plasma, before or after beta-blockade. Maximum dynamic exercise for 4–8 min resulted in an approximate doubling in the cAMP concentration in both muscle and blood. The increase in plasma was closely related to that in muscle. Beta-blockade inhibited totally the rise in cAMP in muscle during exercise but was marginally less effective in preventing the increase in blood. No increase in plasma or muscle cAMP levels during 40–70 s isometric contraction were observed.     

Age-related impairments in memory and in CREB and pCREB expression in hippocampus and amygdala following inhibitory avoidance training

This experiment examined whether age-related changes in CREB and pCREB contribute to the rapid forgetting seen in aged animals. Young (3-month-old) and aged (24-month-old) Fischer-344 rats received inhibitory avoidance training with a low (0.2 mA, 0.4 s) or moderate (0.5 mA, 0.5 s) foot shock; memory was measured 7 days later. Other rats were euthanized 30 min after training, and CREB and pCREB expression levels were examined in the hippocampus, amygdala, and piriform cortex using immunohistochemistry. CREB levels decreased with age in the hippocampus and amygdala. After training with either shock level, young rats exhibited good memory and increases in pCREB levels in the hippocampus and amygdala. Aged rats exhibited good memory for the moderate but not the low shock but did not show increases in pCREB levels after either shock intensity. These results suggest that decreases in total CREB and in pCREB activation in the hippocampus and amygdala may contribute to rapid forgetting in aged rats. After moderate foot shock, the stable memory in old rats together with absence of CREB activation suggests either that CREB was phosphorylated in a spatiotemporal pattern other than analyzed here or that the stronger training conditions engaged alternate mechanisms that promote long-lasting memory.     

ALA和HMME水凝胶栓剂的制备和体内外释药研究

目的 制备光敏剂5-氨基酮戊酸(ALA)和血卟啉单甲醚(HMME)水凝胶栓剂,评价其对直肠肿瘤组织的光敏剂递送效率.方法 将皮下移植人直肠癌细胞SW837的BALB/c小鼠随机分为水凝胶栓剂直肠局部给药组、皮肤局部给药组、瘤内注射给药组和静脉注射给药组.用荧光光谱仪测量直肠壁、皮肤和皮下肿瘤中原卟啉(PpⅨ)和HMME的浓度,荧光光谱系统测定相应的光敏剂分布情况.结果 ALA水凝胶栓剂直肠局部给药组的PpⅨ浓度分别是皮肤局部给药组的9.76倍(1 h)和5.80倍(3 h),差异均具有统计学意义(均P＜0.05).皮肤局部给药后2h,ALA在肿瘤组织内达到最大穿透深度(3～6 mm).而HMME水凝胶栓剂直肠局部给药后,直肠壁中的HMME浓度极低,且皮肤局部给药后的最大肿瘤穿透深度不足2 mm.结论 与皮肤相比,ALA更易穿透黏膜屏障,以水凝胶栓剂形式直肠局部给药有望成为ALA用于光动力疗法治疗直肠癌的一种给药方式.     

Advances in adult asthma diagnosis and treatment and HEDQ in 2010

This summary reviews research published over the past year on asthma and through the prism of health care delivery and quality. Special attention is given to management, therapeutics, and the role of environmental exposures and their interactions with genetics. The discussion is framed around the 3 stages of translational research: from bench to first studies in human subjects, then to larger efficacy studies in well-defined patient populations, and finally into practice through effectiveness research in real-world settings.     

Ceramide in apoptosis and oxidative stress in allergic inflammation and asthma

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