衣康酸对脓毒症小鼠急性肾损伤的保护作用

The protective effect of Itaconic Acid on acute renal injury in sepsis mice

目的观察脓毒症急性肾损伤小鼠肾组织炎性因子的变化规律并探讨衣康酸对脓毒症小鼠炎性因子的影响以及对脂多糖(LPS)诱导的小鼠急性肾损伤的保护作用。方法雄性C57BL/6小鼠24只,根据随机数字表法将其分为三组:空白对照组、LPS组、衣康酸+LPS组,每组各8只。衣康酸+LPS组腹腔给予50 mg/kg衣康酸,空白对照组和LPS组腹腔给予等量生理盐水。给药2 h后,空白对照组注射等量的生理盐水,其他两组小鼠腹腔注射LPS(10 mg/kg)。24 h后,麻醉小鼠,留取肾组织备用。肾组织切片苏木精-伊红染色观察肾损伤程度。酶联免疫吸附试验法检测血浆中白细胞介素(IL)-1β、IL-6和肿瘤坏死因子-α(TNF-α)水平的变化。Western blot法检测肾组织中细胞外调节蛋白激酶(ERK)、c-Jun氨基末端激酶(JNK)、P38和P65蛋白的磷酸化程度。结果LPS处理24 h后,LPS组肾损伤评分,髓过氧化物酶活性,血浆中IL-1β、IL-6和TNF-α水平,肾组织中ERK、JNK、P38和P65蛋白磷酸化水平均高于对照组,差异有统计学意义(P<0.05),而衣康酸+LPS组低于LPS组,差异有统计学意义(P<0.05)。结论衣康酸对LPS诱导的急性肾损伤有保护作用,可能是抑制丝裂原活化蛋白激酶信号通路介导的炎性反应。

Objective To observe the changes of inflammatory factors in renal tissue of sepsis mice with acute kidney injury and to investigate the effect of Itaconic Acid on inflammatory factors in sepsis mice and the protective effect on lipopolysaccharide(LPS)induced acute kidney injury in mice.Methods A total of 24 male C57BL/6 mice were divided into three groups:blank control group,LPS group,and Ttaconic Acid+LPS group,with 8 mice in each group.A total of 50 mg/kg of Itaconic Acid was given to the abdominal cavity of the Itaconic Acid+LPS group,and the same amount of normal saline was given to the abdominal cavity of the blank control group and the LPS group.After 2 h of administration,the mice in the blank control group were injected with the same amount of normal saline,and the mice in the other two groups were intraperitoneally injected with LPS(10 mg/kg).After 24 h,the mice were anesthetized and kidney tissue was taken for reserve.Renal tissue sections were stained with hematoxylin-eosin to observe the degree of renal injury.Serum levels of interleukin(IL)-1,IL-6 and tumor necrosis factor-α(TNF-α)were determined by enzyme linked immunosorbent assay.Phosphorylation levels of extracellular regulatory protein kinase(ERK),c-Jun amino-terminal kinase(JNK),P38 and P65 proteins in renal tissues were detected by Western blot.Results The renal injury score,MPO activity,the levels of IL-1β,IL-6 and TNF-αin the plasma,the levels of ERK,JNK,P38 and P65 protein phosphorylated in the renal tissue of LPS group were higher than those of the control group,the differences were statistically significant(P<0.05).While those of Itaconic Acid+LPS group were lower than LPS group,the differences were statistically significant(P<0.05).Conclusion Itaconic Acid has a protective effect on LPS-induced acute kidney injury,possibly by inhibiting the inflammatory response mediated by the mitogen-activated protein kinase signal pathway.