微RNA-155激动剂对脓毒症小鼠肝损伤时炎症应答的影响

目的探讨微RNA-155（miR-155）激动剂对脓毒症小鼠肝损伤时炎症应答的影响。 方法将80只雄性小鼠分成假手术组、脓毒症组、微RNA（miRNA）组及miR-155组，每组各20只。以盲肠结扎穿孔（CLP）术制备脓毒症小鼠模型，假手术组除不结扎和穿刺盲肠外，其余手术步骤相同。建模成功后48 h，miRNA组、miR-155组小鼠分别经尾静脉注射miRNA、miR-155激动剂，假手术组和脓毒症组注射等量等渗NaCl溶液。每组取10只用于观察小鼠活动状态及术后7 d存活情况；每组另取10只于术后5 d采集外周血，检测并比较miR-155及丙氨酸转氨酶（ALT）水平；采用酶联免疫吸附测定（ELISA）检测血清白细胞介素10（IL-10）及肿瘤坏死因子α（TNF-α）水平。 结果CLP术后7 d，miR-155组小鼠均死亡，脓毒症组和miRNA组仍有2只存活；而假手术组小鼠10只均存活。CLP术后5 d，4组小鼠间miR-155、ALT、IL-10及TNF-α水平比较，差异均有统计学意义（F = 46.536，P < 0.001；F = 39.194，P = 0.002；F = 39.228，P = 0.002；F = 83.400，P < 0.001）。进一步两两比较发现，脓毒症组、miRNA组及miR-155组小鼠的miR-155、ALT、IL-10及TNF-α水平均显著高于假手术组（P均< 0.05），且与脓毒症组和miRNA组比较，miR-155组小鼠的miR-155、ALT及IL-10水平均较高，而TNF-α水平均较低（P均< 0.05）。 结论miR-155激动剂可提高IL-10水平，降低TNF-α水平，从而加重脓毒症小鼠的肝损伤。

Effect of microRNA-155 agonist on inflammatory response during liver injury in septic mice

ObjectiveTo investigate the effect of microRNA-155 (miR155) agonist on inflammatory response during liver injury in septic mice. MethodsA total of 80 male mice were randomly divided into the sham operation group, sepsis group, microRNA (miRNA) group and miR-155 group, 20 in each group. The model of sepsis was produced by cecal ligation and puncture (CLP), and mice in the sham operation group received the same procedure except for ligation and puncture. Mice in the miRNA group and miR-155 group were given miRNA and miR-155 agonist respectively via the tail vein at 48 h after CLP, and mice in the sham operation group and sepsis group were injected with equal isotonic NaCl solution. Ten mice in each group were used to observe their survival condition on 7 d, and the others in each group were used to collect peripheral blood on 5 d after CLP. The levels of miR-155 and alanine aminotransferase (ALT) were determined and compared. The levels of interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). ResultsOn 7 d after CLP, 10 mice in the miR-155 group all died, 10 mice in the sham operation group all survived, and 2 mice survived in the sepsis group and miRNA group respectively. The levels of serum miR-155, ALT, IL-10 and TNF-α among four groups on 5 d after CLP were significantly different (F = 46.536, P < 0.001; F = 39.194, P = 0.002; F = 39.228, P = 0.002; F = 83.400, P < 0.001). Moreover, the levels of miR-155, ALT, IL-10 and TNF-α in the sepsis group, miRNA group and miR-155 group were significantly higher than those in the sham operation group (all P < 0.05). Compared with the sepsis group and miRNA group, the levels of miR-155, ALT and IL-10 increased obviously, and the level of TNF-α decreased remarkably in the miR-155 group (all P < 0.05). ConclusionThe miR-155 agonist can improve the IL-10 level and reduce the TNF-α level, thereby aggravating liver injury in septic mice.