聚腺苷二磷酸核糖糖苷水解酶调节癫痫大鼠海马组织凋亡诱导因子及炎症因子的研究

目的: 探讨聚腺苷二磷酸核糖糖苷水解酶(PARG)对癫痫大鼠海马神经元损伤的影响及其分子机制,探讨PARG抑制剂单宁酸对凋亡诱导因子(AIF)、白细胞介素1β(IL-1β)和肿瘤坏死因子α (TNF-α)的调节作用。方法: 应用Nissl染色方法检测海藻氨酸致痫大鼠海马神经元在单宁酸干预前后的变化;应用Western blotting检测单宁酸干预前后致痫大鼠海马组织聚腺苷二磷酸核糖、AIF、IL-1β和TNF-α表达的变化。结果: 单宁酸干预明显减少癫痫大鼠损伤海马神经元数目(P<0.05);增加致痫大鼠海马组织聚腺苷二磷酸核糖水平(P<0.05);增加致痫大鼠海马组织线粒体蛋白中AIF含量,降低核蛋白中AIF含量 (P<0.05);可显著降低致痫大鼠海马组织IL-1β和TNF-α蛋白表达(P<0.05)。结论: PARG抑制剂单宁酸可减轻癫痫大鼠海马神经元损伤,阻断线粒体AIF的核转位,抑制海马组织IL-1β和TNF-α的表达。

Poly(adenosine diphosphate ribose) glycohydrolase regulates apoptosis-inducing factor and inflammatory factors in rat hippocampus after seizures

AIM: To investigate the effects and molecular mechanisms of poly(adenosine diphosphate ribose) glycohydrolase(PARG) on rat hippocampus neurons after seizures and to study the effects of gallotannin on the expression of apoptosis-inducing factor(AIF),interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in rat hippocampus after seizures.METHODS: Seizures were induced by kainic acid(KA).The damage of hippocampus neurons was evaluated by Nissl staining.The protein expression levels of poly(adenosine diphosphate ribose)(PAR),AIF,IL-1β and TNF-α were detected by Western blotting analysis.RESULTS: The number of damaged hippocampal pyramidal neurons in gallotannin-treated group was significantly lower than that in KA-treated group(P<0.05).The expression of PAR was increased in gallotannin-treated group compared with KA-treated group(P<0.05).AIF in mitochondrial fraction increased and its accumulation in nucleus fraction decreased in gallotannin-treated group compared with KA-treated group(P<0.05).In addition,gallotannin significantly decreased the protein expression of IL-1β and TNF-α,which were obviously increased in hippocampus after seizures(P<0.05).CONCLUSION: PARG inhibition by gallotannin has the neuroprotective effect on the damage of hippocampal neurons induced by seizures.In addition,gallotannin suppresses the translocation of AIF from mitochondria to nucleus and the expression of IL-1β and TNF-α in rat hippocampus after seizures.