Gp91ds—tat抑制JNK3／c—Jun信号通路减轻缺血／再灌注导致的海马CA1区神经元损伤的研究

Gp91 ds- tat attenuates neuronal damage in hippocampal CA1 region induced by ischemia/reperfusion through inhibiting the JNK3/c -Jun signaling pathway

目的探讨NOX2抑制剂Gp91ds—tat对大鼠海马CA1区神经元缺血／再灌注损伤产生的保护作用是否与JNK3／c—Jun信号通路有关。方法通过四动脉结扎法建立全脑缺血模型。SD大鼠随机分为：假手术组（sham组）、缺血／再灌注组（I／R组）、生理盐水组（Saline组）、Gp91ds—tat组（Gp组）。Saline组、Gp组于全脑缺血前20min分别经侧脑室注射生理盐水和Gp91ds—tat（0．4μg/kg）。运用蛋白免疫印迹法检测大鼠海马CA1区JNK3、P—JNK3、c—Jun与P—c—Jun的变化；焦油紫染色法观察海马CA1区神经元的存活情况。结果在缺血复灌1天时，与I／R组相比，Gp组JNK3、c—Jun磷酸化水平明显降低（P〈0．05），而JNK3、c—Jun蛋门含量没有明显变化。同时焦油紫结果显示Gp组神经元的存活数量明显多于I／R组（P〈0．05）。结论Gp91ds—tat对大鼠海马CA1区神经元缺血／再灌注损伤具有保护作用。这作用可能是通过抑制JNK3／c—Jun信号通路实现的。

Objective To investigate whether the protective effects of NOX2 inhibitor Gp91ds - tat on neuronal is- ehemia/repeffusion damage in rat hippocampal CA1 region are associated with inhibition of the JNK3/c - Jun signaling pathway. Methods A brain isehemia nlodel of rats was established using the four - vessel occlusion methods. SD rats were randomly divided into a sham group, an isehemia/repeffusion （I/R） group, a normal saline group and a Gp91 - tat （Gp） group. The normal saline and Gp groups were injected with normal saline and 0.4 pog/kg Gp91ds -tat into the lat- eral ventricle 20 rain before global cerebral isehemia. The levels of JNK3, P - JNK3, c - Jun and P - e - Jun in hipp- oeampal CAI region of rats were detected by immunoblotting. The survival of neurons was observed in hippoeampal CA1 region. Results On Day 1 of I/R, compared with the I/R group, the Gp group showed remarkable decreases in the lev- els of phosphorylated JNK3 and c - Jun （P 〈 0.05）. Meanwhile, the number of viable neurons were higher in the Gp group than those in the I/R group （P 〈 0.05）. Conclusions Gp91ds -tat has protective effects on the I/R damage of hippocampal CA1 neurons in rats, which may be achieved through inhibiting the JNK3/c -Jun signaling pathway.