连续性高容量血液滤过对重症胰腺炎患者血液中IRAK-4表达的影响

Influence of continuous high-volume hemofiltration on IRAK-4 protein expression in severe acute pancreatitis

目的探讨连续性高容量血液滤过(CHVHF)对重症急性胰腺炎(SAP)患者IRAK-4、TNF-α表达的影响和临床意义。方法SPA患者41例随机分为两组,CHVHF+常规治疗组21例,常规治疗组20例。治疗前及治疗开始后24、48和72h采集静脉血,分离出单核细胞,留取血清;同时对患者行APACHEⅡ评分。采用ELISA法检测血清中TNF-α,RT-PCR分析单核细胞中IRAK-4mRNA表达水平,Western blot检测单核细胞中IRAK-4蛋白表达水平。结果CHVHF+常规治疗组21例患者中,存活18例,死亡3例;常规治疗组20例患者中,存活14例,死亡6例。存活患者中,CHVHF+常规治疗组其APACHEⅡ评分下降显著,组内各时间点比较具有统计学意义(P<0.05),治疗开始后与常规治疗组相同时间点相比较,差异均具有统计学意义(P<0.05);TNF-α水平、IRAK-4mRNA水平与蛋白水平在CHVHF开始后24h就开始明显下降,组内及与常规治疗组于治疗开始后同时间点比较均具有统计学意义(P<0.05)。结论CHVHF治疗可降低SAP患者单核细胞中IRAK-4mRNA与蛋白水平及血清中TNF-α含量,显著改善临床症状及预后;其原因可能为CHVHF清除了血清中单核细胞的活化因子,抑制了TLR受体介导的单核细胞激活。

Objective To investigate the influence of continuous high-volume hemofiltration （CHVHF） on intedeukin 1 receptor-associated kinase-4 （IRAK-4） and tumor necrosis factor-or （TNF-α） levels in patients with severe acute pancreatitis （SAP）. Methods Forty-one patients with SAP were randomly divided into two groups to receive treatment with CHVHF plus conventional therapy （21 patients） and conventional therapy only （20 patients）. Venous blood samples were taken before and 12, 24, and 72 h after the treatment for evaluation of APACHE Ⅱ scores. The mRNA and protein levels of IRAK-4 in the monoctyes were determined by real-time PCR and Western blotting, respectively, and serum TNF-α levels was detected using enzyme-linked immunosorbent assay （ELISA）. Results Among the 21 patients receiving CHVHF, 18 survived and 3 died, and in the conventional therapy group, death occurred in 5 cases. In the surviving patients of CHVHF group, the APACHE Ⅱ scores, I1LAK-4 mRNA and protein levels and TNF-α levels were all significantly lowered after the treatment, and these indices were also significantly lower than those in the conventional group after treatment （P〈0.05）. Conclusion CHVHF is effective in reducing monocyte I1LAK-4 levels and serum TNF-α level in SPA patients, and thus alleviates the symptoms and improves the prognosis of SAP, possibly by reducing the level of the activators that induce monocyte activation via the Toll-like receptor.