连续性肾脏替代治疗对急性肾损伤患者自噬相关蛋白表达及预后的影响

Effect of continuous renal replacement therapy on mRNA expression of autophagy-related molecules and prognosis in patients with acute kidney injury

目的:探讨连续性肾脏替代治疗(CRRT)对急性肾损伤(AKI)患者自噬相关蛋白表达及预后的影响。方法:选取2015年2月~2018年3月于杭州师范大学附属医院被诊断为AKI并接受CRRT的患者共计174例。比较CRRT治疗前后患者血浆白细胞介素1β(IL-1β)和白细胞介素6(IL-6)蛋白水平及血单核细胞中微管相关蛋白1轻链3-Ⅱ(LC3-Ⅱ)、自噬相关蛋白5(Atg5)和beclin-1的mRNA表达水平,并进一步分析上述分子的表达水平与患者血清肌酐(SCr)的相关性。根据治疗4周后的生存情况,将入选患者分为死亡组(n=43)和生存组(n=131),对两组患者上述指标的水平进行比较。结果:CRRT后,患者外周血的IL-1β、IL-6和SCr水平均较治疗前显著下降(P<0.05),LC3-Ⅱ、Atg5和beclin-1的mRNA表达水平显著降低(P<0.05)。死亡组患者LC3-Ⅱ、Atg5和beclin-1的mRNA表达水平显著高于生存组(P<0.05)。IL-1β、IL-6、LC3-Ⅱ和beclin-1的表达水平与SCr呈正相关(P<0.05),然而Atg5的表达水平与SCr无显著相关性(P>0.05)。结论:CRRT能够降低AKI患者外周血自噬相关分子的mRNA表达水平,进而降低自噬水平,对AKI患者发挥保护性作用。自噬相关分子的mRNA可作为预测CRRT预后的重要指标。

AIM:To explore the effect of continuous renal replacement therapy(CRRT)on mRNA expression of autophagy-related molecules and the prognosis in the patients with acute kidney injury(AKI).METHODS:A total of174 patients from our hospital who were diagnosed to have AKI and underwent CRRT between February 2015 and March2018 were involved in this study.The plasma levels of interleukin-1β(IL-1β)and interleukin-6(IL-6),the serum creatinine(SCr)level,and the mRNA expression levels of autophagy-related molecules,including microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ),autophagy-related protein 5(Atg5)and beclin-1,in the monocytes from peripheral blood were compared before and after CRRT.According to the survival of AKI patients after 4 weeks of CRRT,the enrolled patients were divided into death group(n=43)and survival group(n=131),and the mRNA expression levels of the above molecules were compared between the 2 groups.RESULTS:After CRRT treatment,the plasma levels of IL-1β and IL-6,the level of SCr,and the mRNA expression levels of LC3-Ⅱ,Atg5 and beclin-1 in the monocytes were significantly lower than those before CRRT treatment(P<0.05).The mRNA expression levels of LC3-Ⅱ,Atg5 and beclin-1 in death group were significantly higher than those in survival group(P<0.05).The positive correlation between SCr and IL-1β,IL-6,LC3-Ⅱ or beclin-1 was observed(P<0.05),and no correlation between SCr and Atg5 was found(P>0.05).CONCLUSION:CRRT decreases the mRNA expression levels of autophagy-related molecules in the patients with AKI and reduces the autophagy activity,which is protective for the patients.These autophagy-related molecules may be applied as a potential markers to predict the prognosis of CRRT.