乌司他丁经p38MAPK通路对脓毒症大鼠急性肾损伤影响的研究  

Ulinastatin protects against acute kidney injury in septic rats via p38MAPK signaling pathway

作　　者：王敏 刘虹[2] Wang Min;Liu Hong(Department of General Practice,Shanxi Bethune Hospital(Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital),Third Hospital of Shanxi Medical University,Taiyuan 030032,China;Department of Critical Care Medicine,First Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西白求恩医院(山西医学科学院同济山西医院)山西医科大学第三医院综合医疗科,太原030032 [2]山西医科大学第一医院重症医学科,太原030001

出　　处：《中华临床医师杂志（电子版）》2022年第6期566-571,共6页Chinese Journal of Clinicians(Electronic Edition)

摘　　要：目的研究乌司他丁(UTI)经p38MAPK通路对脓毒症大鼠急性肾损伤(AKI)的影响。方法采用脂多糖(LPS)诱导脓毒症AKI大鼠模型,将32只SD大鼠随机分为4组,空白对照组、脂多糖组(LPS组)、乌司他丁处理组(LPS+UTI组)、p38MAPK阻断剂干预组(LPS+SB组),采用酶联免疫吸附试验(ELISA)法检测肾组织中肿瘤坏死因子α(TNF-α)和转化生长因子(TGF-β1)的表达,采用蛋白质免疫印迹试验(WesternBlotting)检测肾组织中磷酸化p38MAPK蛋白的表达,并在光镜和电镜下观察肾小球及肾小管的变化。结果与空白对照组相比,LPS组光镜下肾小球充血肿胀,肾球囊扩张,近曲肾小管上皮细胞肿胀明显,细胞核淡染,部分出现核浓缩、破碎甚至溶解现象,肾间质充血、水肿、大量炎性细胞浸润;电镜下肾小球毛细血管内皮细胞窗孔消失或闭塞,基底膜部分断裂消失,足细胞足突广泛融合消失,近曲肾小管上皮细胞质内线粒体排列紊乱,结构模糊,高度肿胀,有空泡样现象;均提示脓毒症肾损伤严重,且肾组织TNF-α、TGF-β1和p38MAPK蛋白的表达明显升高。与LPS组相比,LPS+UTI组肾组织TNF-α、TGF-β1和p38MAPK蛋白的表达均较LPS组下降[TNF-α(pg/ml):4915.00±267.06 vs 8836.00±739.51;TGF-β1(pg/ml):257.71±23.88 vs 354.39±29.44;p-p38MAPK/β-actin:0.158±0.022 vs 0.300±0.044,均P<0.05],LPS+SB组肾组织中TNF-α、TGF-β1和p38MAPK蛋白的表达较LPS组均下降[TNF-α(pg/ml):4856.75±167.23 vs 8836.00±739.51;TGF-β1(pg/ml):249.56±23.42 vs 354.39±29.44;p-p38MAPK/β-actin:0.136±0.017 vs 0.300±0.044,均P<0.05],但LPS+UTI组与LPS+SB组差异无统计学意义(P>0.05)。结论乌司他丁对脓毒症急性肾损伤有保护作用,且可能是通过抑制TGF-β1/p38MAPK信号转导通路来实现的。Objective To study the effect of ulinastatin(UTI)on acute kidney injury(AKI)in septic rats and explore the possible mechanism involved.Methods Thirty-two SD rats were randomly divided into four groups:blank control group,lipopolysaccharide group(LPS group),ulinastatin treatment group(LPS+UTI group),and p38 MAPK blocker intervention group(LPS+SB group).A rat model of sepsis was induced by LPS.The expression of TNF-αand TGF-β1 in renal tissues was detected by ELISA,and the expression of phosphorylated p38 MAPK protein in renal tissues was detected by Western blot.The pathomorphological changes of glomeruli and renal tubules were observed by light microscopy and electron microscopy.Results Compared with the blank control group,the LPS group showed glomerular hyperemia and swelling,renal balloon dilation,obvious swelling of proximal convoluted renal tubule epithelial cells,weak nuclear staining,partial nuclear concentration,breakage,and even dissolution,renal interstitial hyperemia,edema,and a large amount of inflammatory cell infiltration.Electron microscopy showed that the endothelial cells of glomerular capillaries disappeared or were occluded,the basement membrane partially fractured and disappeared,the foot processes of podiocytes extensively fused and disappeared,and the mitochondria in the epithelial cytoplasm of proximal convoluted renal tubules were disorganized,with a fuzzy structure,marked swelling,and vacuolated phenomenon.The expression of TNF-α,TGF-β1,and p38 MAPK proteins in renal tissues increased significantly.Compared with the LPS group,the expression of TNF-α,TGF-β1,and p38 MAPK proteins in the LPS+UTI group was decreased compared with the LPS group[TNF-α(pg/ml):4915.00±267.06 vs 8836.00±739.51;TGF-β1(pg/ml):257.71±23.88 vs 354.39±29.44;P-p38 MAPK/β-actin:0.158±0.022 vs 0.300±0.044,P<0.05].The expression of TNF-α,TGF-β1,and p38 MAPK proteins in the LPS+SB group was decreased compared with the LPS group[TNFα(pg/ml):4856.75±167.23 vs 8836.00±739.51;TGFβ1(pg/ml):249.56±23.42 vs 3

关 键 词：脓毒症 急性肾损伤 乌司他丁 P38MAPK信号转导通路 

分 类 号：R459.7[医药卫生—急诊医学] R692[医药卫生—治疗学]