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中性粒细胞明胶酶相关脂质运载蛋白通过抑制细胞凋亡减轻大鼠盲肠结扎穿刺脓毒症模型中的损伤。

Neutrophil gelatinase-associated lipocalin attenuates injury in the rat cecal ligation and puncture model of sepsis via apoptosis inhibition.

作者信息

Zhao Shuangping, Wei Yangjing, Xu Daomiao

机构信息

Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

Nephrology (Carlton). 2015 Sep;20(9):646-53. doi: 10.1111/nep.12498.

Abstract

AIM

The aim of this study was to investigate the effect of neutrophil gelatinase-associated lipocalin (NGAL) on the rat cecal ligation and puncture (CLP)-induced sepsis and the possible mechanism.

METHODS

Thirty male Sprague-Dawley rats underwent CLP as sepsis models and were randomized into three groups including the sham-operated group (sham, n = 10), which only underwent a laparotomy; the sepsis group (sepsis, n = 10), which underwent CLP and subcutaneous injection of normal saline; and the sepsis + NGAL group (sepsis + NGAL, n = 10), which underwent CLP and subcutaneous injection of NGAL. Urine, blood and kidney tissue samples were collected for the determination of urine NGAL (uNGAL), plasma NGAL (pNGAL), serum creatinine (Scr), blood urea nitrogen (BUN), histomorphological and immunohistochemical examination, lipid peroxidation product malondialdehyde (MDA) and superoxide dismutase (SOD), and expression of heme oxygenase-1 (HO)-1.

RESULTS

The levels of uNGAL, pNGAL, Scr, BUN, kidney injury score, positive TUNEL staining, activated Caspase-3 and Bax, and kidney tissue MDA levels in the sepsis group were significantly increased compared with those in the sham-operated group and the sepsis + NGAL group (P < 0.05). SOD level and HO-1 expression in sepsis + NGAL group were significantly higher than those in the sham-operated group and the sepsis group (P < 0.05).

CONCLUSION

NGAL can attenuate kidney injury and apoptosis in the rat CLP model of sepsis. And the protective effect of NGAL was probably due to the inhibition of apoptosis and lipid peroxidation, and increased expression of HO-1.

摘要

目的

本研究旨在探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL)对大鼠盲肠结扎穿刺(CLP)诱导的脓毒症的影响及其可能机制。

方法

30只雄性Sprague-Dawley大鼠接受CLP手术作为脓毒症模型,随机分为三组,包括假手术组(假手术,n = 10),仅接受剖腹手术;脓毒症组(脓毒症,n = 10),接受CLP手术并皮下注射生理盐水;脓毒症+NGAL组(脓毒症+NGAL,n = 10),接受CLP手术并皮下注射NGAL。收集尿液、血液和肾脏组织样本,用于测定尿NGAL(uNGAL)、血浆NGAL(pNGAL)、血清肌酐(Scr)、血尿素氮(BUN),进行组织形态学和免疫组化检查,测定脂质过氧化产物丙二醛(MDA)和超氧化物歧化酶(SOD),以及血红素加氧酶-1(HO)-1的表达。

结果

与假手术组和脓毒症+NGAL组相比,脓毒症组的uNGAL、pNGAL、Scr、BUN水平、肾脏损伤评分、TUNEL染色阳性、活化的Caspase-3和Bax以及肾脏组织MDA水平显著升高(P < 0.05)。脓毒症+NGAL组的SOD水平和HO-1表达显著高于假手术组和脓毒症组(P < 0.05)。

结论

NGAL可减轻大鼠CLP脓毒症模型中的肾脏损伤和细胞凋亡。NGAL的保护作用可能是由于抑制细胞凋亡和脂质过氧化,并增加HO-1的表达。

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