【摘 要】
：
目的 探讨高容量血液滤过(HVHF)治疗多脏器功能障碍综合征(multiple organ dysfunction syndrome,MODS)对内质网应激相关性细胞凋亡及应激标志蛋白Caspase-12基因水平及表达
【机 构】
：
新疆医科大学第一附属医院肾病科,新疆伊犁州新华医院肾病科
论文部分内容阅读
目的 探讨高容量血液滤过(HVHF)治疗多脏器功能障碍综合征(multiple organ dysfunction syndrome,MODS)对内质网应激相关性细胞凋亡及应激标志蛋白Caspase-12基因水平及表达的影响,并探讨高容量血液滤过(high volume hemofiltration,HVHF)治疗MODS的机制.方法 经二次打击建立犬MODS模型.分HVHF组和MODS组,于术前(T1)、内毒素注射完后Oh (T2)、6h (T3)、12h(T4)及24h(T5)留血标本.体内实验:应用荧光定量PCR法检测肝、肾及肺组织Caspase 12mRNA基因表达水平.体外实验:2组血清体外诱导人脐静脉内皮细胞(HUVECs)建立内质网应激凋亡模型.测定siRNA干扰前后Caspase-12mRNA基因表达、蛋白表达及内皮细胞凋亡率.结果 体内实验:与MODS组相比,HVHF组肾、肺组织Caspase-12mRNA基因表达水平明显降低,差异有统计学意义(P＜0.05),而肝组织Caspase-12mRNA基因表达水平无明显差异(P＞0.05).体外实验:干扰前与MODS组相比,HVHF组在T2-T5 HUVECs Caspase-12mRNA基因表达水平、Caspase-12蛋白表达水平及细胞凋亡率均明显降低,差异有统计学意义(P＜0.01).干扰后2组HUVECs Caspase-12mRNA基因表达水平、Caspase-12蛋白表达水平及细胞凋亡率均较干扰前显著降低,差异有统计学意义(P＜0.01). 结论 内质网应激凋亡信号通路在MODS演进过程中占重要地位,经过HVHF治疗后内质网应激(ERS)凋亡信号通路中的关键蛋白Caspase-12基因表达、Caspase-12蛋白表达水平及细胞凋亡率均明显下降,此作用有助于减轻机体细胞凋亡程度,有效地救治MODS.而RNA干扰(RNAi)技术有望成为治疗MODS新的治疗靶点.
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