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目的观察大鼠局灶脑缺血再灌注(Ischemia-reperfusion,I/R)后脑实质生长抑制与DNA损伤修复相关基因β(Growth arrest and DNA-damage inducible geneβ,Gadd45β)的表达变化,探讨其神经保护作用及机制。方法将SD大鼠随机分为正常对照组、假手术组、脑I/R对照组和四氢化吡咯二硫代氨基甲酸酯(PDTC)组,采用线栓法复制大鼠大脑中动脉缺血再灌注模型,假手术组和脑I/R对照组均在缺血再灌注后经腹腔注射生理盐水,PDTC组经腹腔注射等剂量的PDTC(100 mg/kg)。采用Zea Longa评分法对患肢运动功能进行评分,免疫组化法检测缺血灶周边脑组织中Gadd45β蛋白的表达,RT-PCR法检测缺血灶周边脑组织中Gadd45βmRNA的表达。结果脑I/R对照组和PDTC组大鼠在各时间点神经功能缺损评分呈相同变化趋势,PDTC组大鼠在72 h神经功能缺损评分显著高于脑I/R对照组(P﹤0.05)。脑I/R对照组大鼠缺血灶周边脑组织中Gadd45β蛋白的表达在缺血再灌注后6 h开始增高,24 h达高峰,之后开始下降,但仍高于假手术组(P﹤0.05);PDTC组大鼠Gadd45β蛋白的表达在各个时间点均明显低于脑I/R对照组(P﹤0.05);脑I/R对照组大鼠Gadd45β基因mRNA在12 h的表达明显高于假手术组,24 h达高峰,之后开始下降,但72 h仍高于假手术组(P<0.05);PDTC组大鼠Gadd45β基因mRNA的表达在各个时间点均明显低于脑I/R对照组(P﹤0.05)。结论 PDTC可抑制大鼠脑缺血灶周边脑组织中Gadd45β的表达,Gadd45β可能具有神经保护作用。
Objective To observe the changes of growth arrest and DNA-damage inducible geneβ (Gadd45β) after focal cerebral ischemia-reperfusion (I / R) Protection and mechanism. Methods SD rats were randomly divided into normal control group, sham operation group, brain I / R control group and PDTC group. The middle cerebral artery occlusion Rats in reperfusion group, sham operation group and brain I / R control group were injected intraperitoneally with normal saline after ischemia / reperfusion, and PDTC group was injected intraperitoneally with equal dose of PDTC (100 mg / kg). The limb movement function was evaluated by Zea Longa score method. The expression of Gadd45β protein in the peri-ischemic brain tissue was detected by immunohistochemical method. The expression of Gadd45β mRNA in the peri-ischemic brain tissue was detected by RT-PCR. Results Neurological deficit scores of rats in I / R control group and PDTC group showed the same trend at each time point. The score of neurological deficit in PDTC group at 72 h was significantly higher than that in cerebral I / R control group (P <0.05) . The expression of Gadd45βprotein in cerebral I / R control group began to increase at 6 h after ischemia-reperfusion and peaked at 24 h, then decreased, but still higher than that in sham-operated group (P <0.05) ). The expression of Gadd45βprotein in PDTC group was significantly lower than that in brain I / R control group at each time point (P <0.05). The expression of Gadd45β mRNA in brain I / R control group was significantly higher than that of the control (P <0.05). The expression of Gadd45β mRNA in PDTC group was significantly lower than that in brain I / R control group at each time point (P <0.05). Conclusion PDTC can inhibit the expression of Gadd45β in peripheral brain tissue of rats with cerebral ischemia, and Gadd45β may have neuroprotective effect.