Objective To investigate the protective effect and mechanism of low dose glueocorticoid (GC)on sepsis induced acute kidney injury(AKI)in rat.Methods Eighty healthy Wistar male rats were randomly divided into sham group(n=10),AKI model group(AKI group,n=35)and hydrocortisone treatment group(HC group,n=35),according to random digital table.Septic AKI model was reproduced using cecal ligation and puncture(CLP).After the procedure hydrocortisone 6 mg/kg was injected via sublingual vein in HC group.At 24 hours after the procedure,blood was obtained and the animals were sacrificed in all groups.Pathological changes in the kidney were observed with hematoxylin eosin(HE)staining.The expressions of glucocorticoid receptor alpha(GR-α)and nuclear transcription factor-κB (NF-κB)in the kidney were assessed by immunohistochemistry.The levels of tumor necrosis factor alpha (TNF-α)and interleukins(IL-1β,IL-6,IL-10)in the plasma were determined by enzyme-linked swollen and exfoliated,with loss and vacuolation of tubular brush border under light microscope in AKI expression of GR-α was increased[absorbance(A)value:0.35±0.05 vs.0.25±0.05,P<0.01] and the expression of NF-κB was decreased in HC group(A value:0.23±0.04 vs.0.34±0.04,P<0.01).Compared with AKI group,the levels of TNF-α,IL-1β,IL-6 were lowered[TNF-α(ng/L):94.25±7.96vs.118.24±6.63;IL-1β(ng/L):19.14±1.99 vs.28.91±6.81; IL-6(ng/L): 66.32±1.99 vs.85.70±11.54;all P<0.01] and the level of IL-10(ng/L)was elevated(98.33±6.68 vs.88.59±7.34,P<0.01)in HC group.Conclusion A low dose of hydrocortisone can inhibit the activity of NF-κB,possibly by means of increasing the expression of renal GR-α in septic rats.Accordingly it reduces the production of pro-inflammatory factors which participate in sepsis.So it effectively inhibits inflammation in sepsis and protects the kidney in septic rats.%目的 探讨小剂量糖皮质激素(GC)对脓毒症导致急性肾损伤(AKI)大鼠肾脏的保护作用及其机制.方法 将80只雄性Wistar大鼠按随机数字表法分为假手术组(10只)、AKI模型组(35只)和氢化可的松治疗组(HC组,35只).采用盲肠结扎穿孔术(CLP)复制脓毒症AKI模型.HC组术后经舌下静脉注射氢化可的松6mg/kg.各组于术后24 h取血后处死动物,用苏木素-伊红(HE)染色观察肾脏组织病理学改变;免疫组化法检测肾组织糖皮质激素受体-α(GR-α)、核转录因子-κB(NF-κB)表达;酶联免疫吸附法(ELISA)测定血浆肿瘤坏死因子-α(TNF-α)、白细胞介素(IL-1β、IL-6、IL-10)水平.结果 ①AKI模型组和HC组大鼠存活率差异无统计学意义(42.8%比48.6%,P>0.05).②光镜下观察AKI模型组肾小管上皮细胞肿胀、脱落、刷状缘消失、空泡变性,HC组肾小管病理损害减轻.③与AKI模型组比较,HC组肾脏GR-α表达[吸光度(A值)]增多(0.35±0.05比0.25±0.05,P<0.01),NF-κB表达(A值)减少(0.23±0.04比0.34±0.04,P<0.01);血浆TNF-α、IL-1β、IL-6含量减少[TNF-α(ng/L):94.25±7.96比118.24±6.63)IL-1β(ng/L):19.14±1.99比28.91±6.81;IL-6(ng/L):66.32±1.99比85.70±11.54,均P<0.01],IL-10含量(ng/L)增多(98.33±6.68比88.59±7.34,P<0.01).结论 小剂量氢化可的松可能通过上调脓毒症大鼠肾脏GR-α的表达,抑制NF-κB活性,降低炎症因子产生,有效抑制炎症反应,从而对脓毒症大鼠肾脏起到保护作用.
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