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不同鼠龄脓毒症大鼠血浆早期急性肾损伤标志物的变化
作者:姜生茂 毛智 胡新 虎磐 齐霜 李彦波 周飞虎 
单位:100853  北京 解放军医学院(姜生茂、毛智、胡新、虎磐、齐霜、李彦波、周飞虎) 100853  北京 解放军总医院第一医学中心重症医学科(毛智、胡新、周飞虎) 
关键词:急性肾损伤 脓毒症 生物标志物 
分类号:R631.4
出版年,卷(期):页码:2019,44(6):466-470
摘要:

 [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[12月龄大鼠以D-半乳糖500 mg/(kg.d)诱导6]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3CLP术前0.5 h,术后0.54.58.5 h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)[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0.5 h比较,3组动物血浆Cr在术后0.54.58.5 h均升高(P<0.05);成年组血浆IL-6BUN 在术后4.5 h下降[(121.1±14.9) pg/ml vs. (98.24±13.37) pg/mlP=0.009(5.43±0.73) mmol/L vs. (5.06±0.82) mmol/LP=0.041],但仅青年组达到AKI;与成年组比较,青年组血浆IL-6TIMP-2[TIMP-2]*[IGFBP-7]CLP术后4.5 h升高[分别为(98.24±13.37) pg/ml vs. (116.86±19.75) pg/mlP=0.046(4042.56±781.68) pg/ml vs. (5662.57±1527.8) pg/mlP=0.013(0.112±0.03) (ng/ml)2/1000 vs. (0.17±0.052) (ng/ml) 2/1000P=0.021],血浆BUNCLP术后8.5 h升高[(5.34±0.43) mmol/L vs. (6.29±0.51) mmol/LP=0.017];其余各组CLP术后不同时间点与CLP术前0.5 h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。

 [Abstract]  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-galactose-induced 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 between-group difference (P>0.05). Conclusion  Only the young rats suffered earlier and more serious sepsis-induced AKI. Plasma level of Cr may be useful for early detection of sepsis. Age may not be a risk factor for early AKI in sepsis. Plasma TIMP-2, [TIMP-2]*[IGFBP-7] are potential markers for the detection of early AKI in sepsis in both young and adult animals.

基金项目:
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)
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