不同鼠龄脓毒症大鼠血浆早期急性肾损伤标志物的变化  

Evaluation of age-related changes of early kidney injury markers in plasma of septic rats

作　　者：姜生茂 毛智 胡新[1,2] 虎磐 齐霜[1] 李彦波 周飞虎 JIANG Sheng-mao;MAO Zhi;HU Xin;HU Pan;QI Shuang;LI Yan-bo;ZHOU Fei-hu(Chinese PLA Medical School,100853 Beijing,China;Department of Critical Care Medicine,the First Medical Center of Chinese PLA General Hospital,100853 Beijing,China)

机构地区：[1]解放军医学院,北京100853 [2]解放军总医院第一医学中心重症医学科,北京100853

出　　处：《解放军医学杂志》2019年第6期466-470,共5页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金面上项目(81871581);国家老年疾病临床医学研究中心课题(NCRCG-PLAGH-2017008)~~

摘　　要：目的 比较不同鼠龄脓毒症大鼠血浆早期急性肾损伤(AKI)标志物变化,为不同年龄AKI的早期发现提供参考。方法 21只雄性SD大鼠按鼠龄分为青年组(12周龄)、成年组(12月龄)和老年组[由12月龄大鼠以D-半乳糖500mg/(kg.d)诱导6周]3组,每组7只,均通过盲肠结扎穿孔(CLP)建立脓毒症模型。检测3组CLP术前0.5h,术后0.5、4.5、8.5h的血浆肌酐(Cr)、尿素氮(BUN)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肾损伤分子-1(KIM-1)、白介素-6(IL-6)、胱抑素C(CysC)、金属蛋白酶组织抑制因子-2(TIMP-2)、胰岛素样生长因子结合蛋白-7(IGFBP-7)和[TIMP-2]*[IGFBP-7]水平;血浆Cr升高值≥1.5倍基线值水平定义为AKI。比较不同鼠龄组以及CLP术后不同时间点血浆AKI标志物变化。结果 与CLP术前0.5h比较,3组动物血浆Cr在术后0.5、4.5、8.5h均升高(P<0.05);成年组血浆IL-6、BUN在术后4.5h下降[(121.1±14.9)pg/mlvs.(98.24±13.37)pg/ml,P=0.009;(5.43±0.73)mmol/Lvs.(5.06±0.82)mmol/L,P=0.041],但仅青年组达到AKI;与成年组比较,青年组血浆IL-6、TIMP-2、[TIMP-2]*[IGFBP-7]在CLP术后4.5h升高[分别为(98.24±13.37)pg/mlvs.(116.86±19.75)pg/ml,P=0.046;(4042.56±781.68)pg/mlvs.(5662.57±1527.8)pg/ml,P=0.013;(0.112±0.03)(ng/ml)^2/1000vs.(0.17±0.052)(ng/ml)2/1000,P=0.021],血浆BUN在CLP术后8.5h升高[(5.34±0.43)mmol/Lvs.(6.29±0.51)mmol/L,P=0.017];其余各组CLP术后不同时间点与CLP术前0.5h相比、相同时间点不同组间比较,血浆AKI标志物变化差异均无统计学意义(P>0.05)。结论 青年组脓毒症大鼠AKI出现较早且较重,血浆Cr水平监测有助于其早期发现;年龄可能不是早期脓毒性AKI的影响因素;血浆TIMP-2、[TIMP-2]*[IGFBP-7]可能有助于对青年组和成年组的脓毒症早期AKI进行判断。Objective To evaluate age-related changes of early plasma renal injury markers in rats with sepsis,which can serve as evidence for the early detection of acute kidney injury(AKI).Methods Twenty-one male Sprague Dawley rats were divided into 3 groups based on their age:young group(12 weeks,n=7),adult group(12 months,n=7),and old group(D-galactoseinduced 12 months,500 mg/(kg.d),for 6 weeks,n=7).All rats were received cecal ligation and puncture(CLP)procedure to induce sepsis.Plasma samples of each rat were collected 0.5 h before CLP,and 0.5 h,4.5 h,8.5 h after CLP.For each sample,plasma level of kidney injury markers,including plasma creatinine(Cr),blood urea nitrogen(BUN),neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),interleukin-6(IL-6),Cystatin C(CysC),insulin-like growth factor-binding protein 7(IGFBP-7),tissue inhibitor of metalloproteinases-2(TIMP-2)and[TIMP-2]*[IGFBP-7]were quantified.We adopted the criteria for AKI:plasma creatinine elevation≥1.5 times of the baseline level.Within-group longitudinal changes and between-group changes were evaluated.Results Compared with samples collected at 0.5 h before CLP,plasma Cr levels were significantly increased at 0.5 h,4.5 h and 8.5 h after CLP in all three groups(P<0.05),while plasma IL-6[(121.1±14.9)pg/ml vs.(98.24±13.37)pg/ml,P=0.009]and BUN[(5.43±0.73)mmol/L vs.(5.06±0.82)mmol/L,P=0.041]significantly decreased at 4.5 h after CLP in adult rats,Only the young rats suffered AKI.In between-group comparison,plasma level of IL-6[(98.24±13.37)pg/ml vs.(116.86±19.75)pg/ml,P=0.046],TIMP-2[(4042.56±781.68)pg/ml vs.(5662.57±1527.8)pg/ml,P=0.013],[TIMP-2]*[IGFBP-7][(0.112±0.03)(ng/ml)2/1000 vs.(0.17±0.052)(ng/ml)^2/1000,P=0.021]significantly increased at 4.5 h after CLP and BUN[(5.34±0.43)mmol/L vs.(6.29±0.51)mmol/L,P=0.017]at 8.5 h after CLP in the young group,compared with the adult rats.There was no significant difference in the plasma levels of other markers when compared with 0.5 h before CLP and also no significant betwe

关 键 词：急性肾损伤 脓毒症 生物标志物 

分 类 号：R631.4[医药卫生—外科学]