内质网应激诱导血管反应性降低与线粒体通透性转换孔开放的关系

 目的:探讨内质网应激是否可诱导血管反应性降低及其与线粒体通透性转换孔开放的关系。方法:利用SD大鼠盲肠结扎穿孔（CLP）脓毒性休克模型,检测不同时点肠系膜上动脉内质网应激标志分子GRP78和CHOP的蛋白质表达水平,同时检测肠系膜上动脉对去甲肾上腺素的反应性;离体血管环观察毒胡萝卜素孵育对肠系膜上动脉血管反应性的影响,并观察线粒体通透性转换孔在其中的作用。结果:大鼠CLP后不同时点肠系膜上动脉GRP78和CHOP表达呈逐渐升高趋势,肠系膜上动脉的反应性降低,用内质网应激抑制剂牛磺酸能够抑制GRP78和CHOP的表达,并显著恢复血管反应性。离体血管环研究表明,毒胡萝卜素能够降低血管反应性,牛磺酸能恢复血管反应性,线粒体通透性转换孔抑制剂环孢素A能显著增加血管反应性。结论: 内质网应激能诱导血管反应性降低,且可能与线粒体通透性转换孔有关。

Endoplasmic reticulum stress induces vascular hyporeactivity and its relationship with mitochondrial permeability transition pore

AIM: To explore whether endoplasmic reticulum stress induces vascular hyporeactivity in septic shock rat and its relationship with mitochondrial permeability transition pore (MPTP). METHODS: The rat model of septic shock was established by cecal ligation and puncture. The protein expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) was measured by Western blotting. The reactivity of superior mesenteric artery (SMA) to norepinephrine (NE) was observed. Isolated rat SMAs were incubated with thapsin to observe the change of reactivity to NE and the relationship to MPTP. RESULTS: The protein expression of GRP78 and CHOP in septic shock rats was increased, while the reactivity of SMA to NE was declined in a time-dependent manner. Taurine, an endoplasmic reticulum stress inhibitor, down-regulated the expression of GRP78 and CHOP, and restored the vascular reactivity. Incubation of SMA with thapsin significantly decreased the reactivity of SMA to NE, and intervention with taurine abolished the decline of reactivity of SMA. Besides, cyclosporin A, an MPTP closer, greatly increased the reactivity of SMA after treated with thapsin. CONCLUSION: Endoplasmic reticulum stress induces the vascular hyporeactivity in the rat model of septic shock and the opening of MPTP may take part in the process.