Luteoloside attenuates anoxia/reoxygenation‐induced cardiomyocytes injury via mitochondrial pathway mediated by 14‐3‐3η protein

Ischemia/reperfusion (I/R) injury is the major cause of acute cardiovascular disease worldwide. 14‐3‐3η protein has been demonstrated to protect myocardium against I/R injury. Luteoloside (Lut), a flavonoid found in many Chinese herbs, exerts myocardial protection effects. However, the mechanism remains unclear. We hypothesize that the cardioprotective role of Lut is exerted by regulating the 14‐3‐3η signal pathway. To investigate our hypothesis, an in vitro I/R model was generated in H9C2 cardiomyocytes by anoxia/reoxygenation (A/R) treatment. The effects of Lut on cardiomyocytes with A/R injury were assessed by determining the cell viability, lactate dehydrogenase levels, intracellular reactive oxygen species levels, mitochondrial permeability transition pores (mPTP) openness, caspase‐3 activity, and apoptosis rate. The effects on protein expression were tested using western blot analysis. Lut attenuated A/R‐induced injury to cardiomyocytes by increasing the expression of 14‐3‐3η protein and cell viability; decreasing levels of lactate dehydrogenase, reactive oxygen species, mPTP openness, caspase‐3 activity, and low apoptosis rate were observed. However, the cardioprotective effects of Lut were blocked by AD14‐3‐3ηRNAi, an adenovirus knocking down the intracellular 14‐3‐3η expression. In conclusion, to our knowledge, this is the first study to demonstrate that Lut protected cardiomyocytes from A/R‐induced injury via the regulation of 14‐3‐3η signaling pathway.     

Modification of anoxic neuronal injury by human recombinant epidermal growth factor and its possible mechanism

A primary culture of cortical neurons was established from a 17-day rat embryo. Twenty-four hours after plating, the culture medium was changed to a chemically defined one, and human recombinant EGF (rEGF) was added to the medium at concentrations of 1, 10, and 100 ng/ml. Anoxic stress was exerted on the cultured neurons for 4 hr. Without anoxia, rEGF at a concentration of 10 ng/ml supported neuronal survival. When rEGF was not present in the culture medium, anoxic stress reduced neuronal density to one-tenth that of the nonanoxic group. The rEGF improved neuronal recovery from anoxia significantly, with survival dependent on rEGF dosage. Monoclonal antibody for EGF receptors canceled the effect of rEGF on survival of neurons in a dose-dependent manner. Therefore, rEGF functioned to support neuronal survival from anoxia through EGF receptors. Ontogeny of the EGF receptors was detected immunocytochemically with anti-EGF receptor antibody. About 70% of the cultured neurons were stained by the anti-EGF receptor antibody 3 days after change of medium, and immunoreactivity for EGF receptors was found to be located on the soma of neurons. Binding activity of EGF receptors was detected 5 days after change of medium with receptor binding assay and Scatchard analysis. High-affinity binding sites were detected only in neurons cocultured with rEGF (10 ng/ml) for 5 days. The data indicate that rEGF in sufficient concentration induces high-affinity sites of the EGF receptor and that EGF may have an antianoxic effect through the EGF receptors.     

左旋硝基精氨酸抗大鼠海马脑片缺氧损伤的电生理研究

目的 :为进一步证实一氧化氮合酶 ( NOS)抑制剂左旋硝基精氨酸 ( L -NNA)抗缺血缺氧性脑损伤的作用。方法 :在大鼠离体海马脑片 ,用电生理记录技术 ,观察 L-NNA对缺氧时海马脑片顺向群峰电位 ( OPS)的影响。结果 :使用 L-NNA的海马脑片缺氧后 OPS的恢复程度和恢复率分别为 10 4.79± 6 6 .2 5 %、75 .0 0 % ,与对照组相比有显著性差异 ( P<0 .0 5 )。结论 :L-NNA有明显抗缺氧脑损伤作用 ,作用机理可能是 L -NNA抑制了 n NOS活性 ,降低缺氧时神经源性 NO的形成 ,减轻 NO对神经细胞的毒性作用     

Delayed neuropsychiatric sequelae after acute hydrogen sulfide poisoning: affection of motor function, memory, vision and hearing

A shipyard worker was poisoned by hydrogen sulfide (H2S), and rescued after 15-20 min. He regained consciousness after 2 days. Three days later his condition deteriorated, and he was more or less comatose for a month. When he woke up, he was amnesic, nearly blind, had reduced hearing, and had a moderate spastic tetraparesis and ataxia. Two months after the accident, he had greatly improved. Audiograms showed hearing loss with maximum at 2000 Hz and significantly poorer speech discrimination. EEG showed generalized dysrhythmia. At follow-up 5 years later he had not been able to resume his work, and had slight motor, memory and visual symptoms. CT and MRI showed slight cerebral atrophy. EEG and evoked responses were normal.     

新生儿缺氧缺血性脑病合并多器官损害临床分析

【目的】了解缺氧缺血性脑病 (HIE)新生儿心、肝、肾功能及钙、镁、血糖水平的变化状况。【方法】应用日立 7170A全自动生化分析仪对HIE患儿及无窒息新生儿于出生后 3d内所采血样的心肌酶谱、肝功能、尿素氮、钙、镁、血糖进行检测 ,同时检查尿常规。【结果】HIE组患儿心肌酶、肝酶、血总胆红素水平均明显高于对照组 (P <0 .0 5 ) ;HIE组血钙、镁低于对照组 (P <0 .0 1) ;HIE组肾损害发生率、高血糖发生率均高于对照组 (P <0 .0 5 )。【结论】HIE同时可并发多器官功能损害 ,在治疗脑损伤的同时 ,应对其它各器官功能密切监测并加以保护。     

脑内移植BDNF载体细胞对新生大鼠缺氧缺血性脑损伤后运动机能和行为的影响

目的：探讨脑内移植脑源性神经营养因子(BDNF)载体细胞对新生大鼠缺氧缺血性脑损伤后存活、运动机能和行为的影响。方法：7d龄新生大鼠一侧颈总动脉结扎联合低氧吸入法制成缺氧缺血性脑损伤模型。在损伤后即刻，于单侧皮层内植入构建的可稳定表达和分泌BDNF的大鼠成肌细胞，观察植入4周后大鼠存活、运动机能和行为的变化。结果：BDNF载体细胞可稳定表达BDNFmRNA，其分泌上清液可维持PC12细胞存活、促进突触生长，脑内移植后42d，移植组动物死亡率显著降低928.6％，对照值为57.7％）；倾斜临界角度虽仍低于假伤组，但显著高于移植不含BDNF载体细胞的对照组；开场行为的水平、垂直运动值均显著高于对照组，多数时间点上显著低于假伤组。结论：脑内移植可稳定表达和分泌活性BDNF的载体细胞可显著降低新生大鼠缺氧缺血性脑损伤后的死亡率，对运动机能和行为的恢复有良好的促进作用。     

甲基莲心碱纳米脂质体对小鼠脑缺氧以及脑栓塞的疗效观察

目的研究甲基莲心碱（Nef）纳米脂质体（NefNL）对小鼠脑缺氧及脑栓塞的治疗作用。方法用亚硝酸钠制造小鼠脑缺氧模型,诱导剂制造小鼠脑栓塞模型。观察NefNL对这两种小鼠病模的治疗效果,并与生理盐水组、同剂量Nef注射液组、普通Nef脂质体组进行比较。结果与生理盐水组相比,Nef3种制剂均能显著延长小鼠亚硝酸钠中毒后的存活时间,提高小鼠对抗脑栓塞的能力（P〈0.05）;与Nef注射液组、普通Nef脂质体组相比,NefNL的治疗效果均有明显提高（P〈0.05）。结论 NefNL对小鼠脑缺氧以及脑栓塞有明显的预防保护作用。     

胰岛素样生长因子I、生长抑素在新生儿缺氧缺血性脑病血液中水平变化的研究

目的　观察胰岛素样生长因子 I(insulin- like growth factor- I,IGF- I)、生长抑素(som atostatin,SS)在新生儿缺氧缺血性脑病 (hypoxic- ischemic encephalopathy,HIE)极期和恢复期血液中的变化 ;探讨 IGF- I、SS在 HIE发病机制中的作用。　方法　 (1)用放射免疫分析法 (RIA)测定正常对照组、HIE极期、恢复期血浆 SS的水平。(2 )用免疫放射分析 (IRMA)测定上述标本血清中 IGF- I的水平。　结果　 (1) HIE极期、恢复期与正常对照组 IGF- I、SS水平有显著差异 (F=78.7,P<0 .0 1;H=33.3,P<0 .0 1) ,HIE极期 IGF- I、SS水平下降 ,恢复期 IGF- I、SS水平升高。(2 ) HIE轻、中、重度组间 IGF- I、SS水平比较 ,均有显著差异 (F=3.38,P<0 .0 5 ;H=6 .46 ,P<0 .0 5 ) ,病情越重 ,IGF- I、SS水平越低。　结论　 (1) HIE极期 IGF- I、SS水平下降 ,恢复期 IGF- I、SS水平升高 ,提示 IGF- I、SS在 HIE的发病机制中可能具有重要作用。(2 ) HIE时 IGF- I、SS水平下降程度与疾病轻重程度有关。IGF- I、SS检测对临床疾病严重程度的判断可能具有指导意义并可作为病情恢复与否的一个监测指标。