葛根素对缺氧缺血性脑损伤保护作用的研究进展

新生儿缺氧缺血性脑损伤(HIBD)是新生儿死亡和婴幼儿神经系统功能障碍的主要原因,围生期HIBD仍然是神经保护治疗的主要对象。研究HIBD发病机制及相应的治疗措施一直是医学研究的热点。中药制剂在神经保护中的作用亦得到关注。葛根素是由豆科植物野葛的干燥葛根提取物制成,主要化学成分为4,7-二羟基-8-β-D葡萄糖异黄酮。近年来葛根素对HIBD的保护作用得到深入广泛的研究。现就此方面资料予以综述,以期能为葛根素在HIBD中神经保护作用的研究提供一定的参考。     

新生儿缺氧缺血性脑病早期高压氧治疗后SOD、MDA的变化

目的　 研究新生儿缺氧缺血性脑病 (HIE)高压氧治疗后超氧化物歧化酶 (SOD)和丙二醛 (MDA)的变化及其临床意义。 方法 　将 5 5例HIE患儿分为窒息组 ( 5 5例 )、严重窒息组 ( 30例 )和轻度窒息组 ( 2 5例 ) ,患儿均于生后 48h内行高压氧治疗 ,并分别于治疗前后检测SOD和MDA。 结果 　高压氧治疗后 ,窒息组SOD、MDA无显著变化 (P >0 0 5 ) ;严重窒息组患儿MDA上升 (P <0 0 5 ) ,SOD下降 (P <0 0 5 ) ;轻度窒息患儿MDA下降 (P <0 0 5 ) ,SOD无显著变化 (P >0 0 5 )。 结论 　生后 48h内 ,严重窒息的HIE患儿高压氧治疗后 ,可促使自由基增加 ;轻度窒息的HIE患儿行高压氧治疗 ,则有抗自由基损伤的作用     

Hippocampal damage induced by carbon monoxide poisoning and spreading depression is alleviated by chronic treatment with brain derived polypeptides

A model of acute carbon monoxide poisoning combined with spreading depression (SD) induced metabolic stress was used to examine the protective effects of cerebrolysin (CL) on the development of electrophysiological, behavioral and morphological signs of hypoxic damage. Capillary electrodes were implanted into the neocortex and hippocampus of anesthetized rats which were then exposed for 90 min to breathing of 0.8% to 0.5% CO, while 3 to 4 waves of cortical and hippocampal SD were elicited by microinjections of 5% KCl. Duration of SD-provoked depolarization of cerebral cortex and hippocampus was noted. Nine and 18 to 19 days later propagation of SD waves was recorded with the same electrodes and decrease of their amplitude was used as an index of brain damage which was significant in the hippocampus but not in the cortex. CL-treatment (2.5 ml/kg per day) started after CO administration and continued for 14 days significantly improved hippocampal recovery manifested by increased amplitude of SD waves. Behavioral tests performed 10 and 20 days after CO poisoning in the Morris water maze revealed better performance (escape latency 7 s) in the CL-treated than in untreated animals (14 s). Morphological analysis showed marked damage in the hippocampus consonant with electrophysiological and behavioral findings in the same animals. No apparent histological damage was found in rats exposed to CO inhalation alone without the additional SD-provoked depolarization. It is concluded that chronic CL-treatment enhances recovery of hippocampal tissue after hypoxic damage of intermediate severity.     

肺心病患者血浆肾上腺髓质素、神经肽Y与缺氧性肺动脉高压的关系

目的 观察缺氧性肺动脉高压患者血浆肾上腺髓质素（ADM）和神经肽Y（NPY）的水平变化,探讨ADM、NPY与缺氧性肺动脉高压的关系和缺氧性肺动脉高压的发病机制.方法 选择慢性阻塞性肺病（COPD）并肺动脉高压、肺心病患者（HPH组,30例）和健康体检者（对照组,20例）,用放免法测定血浆ADM、NPY的含量,并同时测定其血氧分压和肺动脉压力.结果 （1）HPH组血浆ADM、NPY含量高于对照组（HPH组为65.79±25.72、209.01±42.25,对照组为15.26±3.57、135.52±20.12;t=10.15,7.29;P＜0.01）;（2）血浆ADM、NPY与氧分压呈负相关（r=-0.79,-0.67;P＜0.01）;（3）血浆ADM与NPY呈正相关关系（r=0.48;P＜0.01）.结论 ADM、NPY参与了缺氧性肺动脉高压发生、发展的病理生理过程.     

心肌酶同功酶检测在新生儿缺氧缺血性脑病中的诊断价值

目的：探讨心肌酶同功酶检测在新生儿缺氧缺血性脑病中的诊断价值。方法：对2003年4月～2004年10月在我院住院的50例HIE患儿于入院后取静脉血2ml行心肌酶检测，对照组30例，为同期出生的正常新生儿，对两组检测结果进行比较。结果：HIE组LDH、CK、CK-MB明显高于正常对照组。结论：心肌酶可作为一个敏感的评价脑损害的指标。     

Hedgehog signaling pathway as a new therapeutic target in pancreatic cancer

Pancreatic cancer is one of the most aggressive and difficult cancers to treat. Despite numerous research efforts, limited success has been achieved in the therapeutic management of patients with this disease. In the current review, we focus on one component of morphogenesis signaling, Hedgehog (Hh), with the aim of developing novel, effective therapies for the treatment of pancreatic cancer. Hh signaling contributes to the induction of a malignant phenotype in pancreatic cancer and is responsible for maintaining pancreatic cancer stem cells. In addition, we propose a novel concept linking Hh signaling and tumor hypoxic conditions, and discuss the effects of Hh inhibitors in clinical trials. The Hh signaling pathway may represent a potential therapeutic target for patients with refractory pancreatic cancer.     

Donor preoperative oxygen delivery and post-extubation hypoxia impact donation after circulatory death hypoxic cholangiopathy

AIM: To evaluate donation after circulatory death(DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy(HC) and patient/graft survival] and donor risk-conditions.METHODS: From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS Donor Net included preoperative systolic and diastolic blood pressure, heart rate, p H, SpO_2, PaO_2, FiO_2, and hemoglobin. Mean arterial bloodpressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O_2 content was computed as [hemoglobin(gm/d L) × 1.37(m L O_2/gm) × SpO_2%) +(0.003 × PaO_2)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure 60 mm Hg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry 80% until clamping. Donor hypoxia score was(ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin.RESULTS: The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age(33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion(9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin(10.7 ± 2.2 gm/d L vs 12.3 ± 2.1 gm/d L, P = 0.017), lower preoperative arterial oxygen content(14.8 ± 2.8 m L O_2/100 m L blood vs 16.8 ± 3.3 m L O_2/100 m L blood, P = 0.049), greater hypoxia score 2.0(69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure(92.7 ± 16.2 mm Hg vs 83.8 ± 18.5 mm Hg, P = 0.10). HC was independently associated with age, multi-pressor/redcell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure(r~2 = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2(7.1/year)], compared to our early experience [era 1(2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1(P = 0.03). Era 2 donors had longer times for extubation-to-asystole(14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia(13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia(16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score 2.0 rate(73.1% vs 28.6%, P = 0.006).CONCLUSION: Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates.     

缺氧对重度子痫前期患者胎盘绒毛组织代谢足迹变化的影响

目的:探讨在不同氧浓度下体外培养正常妊娠孕妇及重度子痫前期患者胎盘绒毛组织培养液中代谢足迹的变化。方法:选择正常妊娠组(27例)及重度子痫前期组(27例)孕妇,在胎盘边缘、中间、近脐带处取绒毛组织,分别在1%氧浓度下及6%氧浓度下培养96小时,采用高效液相质谱色谱仪检测培养液中代谢产物,观察不同氧浓度下培养的绒毛组织代谢足迹的变化。结果:两组分别取自1%氧浓度和6%氧浓度下培养的同一胎盘边缘、中间、近脐带3点处胎盘绒毛组织代谢足迹的比较差异无统计学意义(P>0.05);1%氧浓度与6%氧浓度下培养的正常妊娠组胎盘绒毛组织代谢足迹比较,发现545个代谢物差异有统计学意义(P<0.05);1%氧浓度与6%氧浓度下培养的重度子痫前期组胎盘绒毛组织代谢足迹的比较差异无统计学意义(P>0.05),1%氧浓度下培养的正常妊娠组与6%氧浓度下培养的重度子痫前期组胎盘绒毛组织代谢足迹的比较差异无统计学意义(P>0.05)。结论:缺氧可能影响胎盘绒毛组织的代谢,在重度子痫前期的发病机制中起重要作用,而利用高效液相质谱色谱仪的代谢组学技术能测定在不同氧浓度下培养的正常妊娠组和重度子痫前期孕妇胎盘绒毛组织代谢足迹的变化,表明该方法适合于重度子痫前期的代谢组学研究。