Study on protective effect and its mechanism of pretreatment of  Caspase-3 gene inhibiter  on hypoxic-ischemic brain damage in the neonatal rats.

Abstract

Abstract: Objective To study the effect of hypoxia ischemia brain damage (HIBD) of neonatal rats with cerebral cortex apoptosis by gene inhibiter so as to explore the possible mechanism. Methods Model of HIBD was built in neonatal rats, 60 Wistar rats were randomly divided in:control group;HIBD group;obstruct group(HIBD+z-VAD-fmk).Adopting HE dyeing, three animal apoptosis index (AI) in brain and Caspase-3mRNA were detected by TUNEL and RT-PCR. Results Express of Caspase-3mRNA nanomolar in control group was significant heighten in HIBD group(P＜0.01).There was significantly lower express between obstruct group and HIBD group(P＜0.05).AI value changed with Caspase-3mRNA.They had significance positive correlation (r=0.628, P<0.05). Conclusion Express heigten of Caspase-3mRNA leads to histiocytic apoptosis in HIBD group, and lower express of Caspase-3mRNA by z-VAD-fmk, could protect brain of neonatal rats.

Key words: hypoxia ischemia damage, rat, apoptosis, Caspase-3

摘要： 目的观察半胱氨酸蛋白酶(Caspase)抑制剂z-VAD-fmk对于缺血缺氧性脑损伤(hypoxic-ischemic brain damage, HIBD)大鼠脑组织的保护作用, 并探讨其机制。方法 7 d龄Wistar大鼠60只, 随机分为对照组、HIBD组和阻断组, 各20只。HIBD组及阻断组制作HIBD模型, 对照组大鼠分离但不结扎左侧颈总动脉, 术后亦不进行缺氧处理。阻断组在建模后给予z-VAD-fmk, 连续7 d。第8天处死全部动物。分别采用TUNEL法和RT-PCR法检测三组动物脑组织中神经细胞凋亡指数(apoptosis index, AI)和Caspase-3 mRNA。结果对照组、HIBD组、阻断组AI值分别为0.15±0.02、21.36±2.45、10.42±1.62, 三组相比差异有统计学意义(P均＜0.05)。三组脑组织中Caspase-3 mRNA的相对表达量分别为0.016±0.003、0.561±0.067、0.216 ±0.036, 三组相比差异有统计学意义(P均＜0.05)。AI值随Caspase-3 mRNA的升高而升高, 随其降低而降低, 二者之间具有正相关关系(r=0.628, P＜0.05)。结论 z-VAD-fmk对HIBD大鼠脑组织有一定的保护作用, 其机制可能是降低脑组织中Caspase-3 mRNA的表达, 减轻神经细胞凋亡。

关键词: 缺血缺氧性脑损伤, 大鼠, 细胞凋亡, 半胱氨酸蛋白酶-3

CLC Number:

Q426

CHEN Hui-jun, YANG Yang.. Study on protective effect and its mechanism of pretreatment of Caspase-3 gene inhibiter on hypoxic-ischemic brain damage in the neonatal rats.[J]. journal1, 2014, 22(1): 38-40.

陈惠军, 杨旸. 早期应用z-VAD-fmk对新生鼠HIBD的保护作用及其机制研究[J]. 中国儿童保健杂志, 2014, 22(1): 38-40.

References

[1] Okamura T, Miura T, Takuma G, et al.Effector caspase inhibitors on myocardial infarct size and myocyte DNA fragmentation in the ischemia-reperfused ratheart[J].Cardiovasc Res, 2000, 45(3):642-650.
[2] 李荣堂, 杨廷桐, 刘玲玲.缺血和缺血再灌注后交界区心肌细胞Caspase-3mRNA的动态变化与药物影响的研究[J].中原医刊, 2005, 32(18):3-5.
[3] Rice JE, Vannucci RC, Brierley JB.The inflluence of immaturity on hypoxic-ischemic brain damage in the rat[J].Ann Neurol, 1981, 9(2):131-141.
[4] 陈惠军.GM1对新生儿缺氧缺血性脑病IL-1β, NSE, ICAM-1的影响[J].山东医药, 2011, 51(41):39-40.
[5] 张媛媛, 李斐, 金星明, 等.生命早期前爪感觉和精细动作剥夺对大鼠海马Schaffer-CA1通路突触可塑性的影响[J].中国儿童保健杂志, 2010, 18(1):45-47.
[6] Abe T, Kunz A, Shimamura M, et al.The neuroprotective effect of pros-taglandin E2 EP1 receptor inhibition has a wideth erapeutic window, is sustained in time and is not sexually dimorphic[J].J Cereb Blood Flow Metab, 2009, 29(1):66-71.
[7] Xie NL, Zhang W, Li J, et al.Alpha-linolenic acid intake attenuates myocardial ischemia/reperfusioninjurythrough anti-inflammatory and anti-oxidative stress effects in diabetic but not normal rets[J].Aechives of Medical Research, 2011, 42(3):171-181.
[8] Chichkova NV, Shaw J, Galiullina RA, et al.Phytaspasw a relocalisable cell death promoting plant protease with caspase specificity[J].EMBO Journal, 2010, 29(6):1149-1161.
[9] Mami Y, Yayoi E, Toshii I, et al.Quantification of activated and total caspase-14 with newly developed ELISA systems in nirmal and atopic skin[J].J Dermatol Sci, 2011, 61(2):110-117.
[10] Sirbulescu RF, Zupanc CK.Inhibition of caspase-3 mediated apoptosis improves spinal cord repair a regeneration-competent vertebrate system[J].Neu Sci, 2010, 26(2):126-131.
[11] Van Empel VP, Bertrand AT, Hofstra L, et al.Myocyte apoptosis in heart failure[J].Cardiovasc Resc, 2005, 67(1):21-29.
[12] Wang Y, Qin NH.Molecular ang cellular mechanisms of excitotoxic neuronal death[J].Apoptosis, 2010, 7(5):798-806.
[13] Saitoh T, Nakajima T, Takahashi T, et al.Changes in cardiovascular funetion on treatmentof inhibitors of apoptotic signal transduction pathways in left ventricular remodeling after myocardial infarction[J].Cardiovasc Path, 2006, 15(3):130-138.
[14] Niizuma K, Yoshioks H, Chen H, et al.Mitochondrial and apoptotic neuronal death signaling pathways in cerebral ischemia[J].Biochim Biophy Acta, 2010, 1802(1):92-99.
[15] Matsuura S, Egi Y, Yuki S, et al.Mp-124 a novel poly (ADP-ri-bose) polymerase-1(PARP-1)inhibitor ameliorales ischemic brain damage in a non-human primate model[J].Brain Res, 2011, 1410(1):122-131.

Study on protective effect and its mechanism of pretreatment of Caspase-3 gene inhibiter on hypoxic-ischemic brain damage in the neonatal rats.

早期应用z-VAD-fmk对新生鼠HIBD的保护作用及其机制研究

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