Ulinastatin ameliorates acute kidney injury following liver transplantation in rats and humans.

Ulinastatin ameliorates acute kidney injury following liver transplantation in rats and humans.
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乌司他丁可改善大鼠和人类肝移植后的急性肾损伤

DOI:
10.3892/etm.2014.2088
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发表时间:
2015-02
影响因子:
2.7
通讯作者:
Hei Z
Hei Z
中科院分区:
医学4区
文献类型:
--
作者:
Li X;Li X;Chi X;Luo G;Yuan D;Sun G;Hei Z

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急性肾损伤(acute kidney injury,阿基)是奥尔特移植术后常见的并发症,严重影响患者的预后。然而,对于阿基没有有效的治疗方法。本研究的目的是阐明乌司他丁在人类奥尔特中的应用是否可以减少肾损伤和改善肾功能。此外,乌司他丁的潜在机制进行了研究大鼠自体奥尔特(AOLT)模型。共60例接受奥尔特的患者,随机选择在奥尔特手术期间接受乌司他丁(U组; n=30)或生理盐水(C组; n=30)。在围手术期测量患者人口统计学资料、阿基发生率、恢复指标和肾损伤指标。除临床试验外,还对40只大鼠进行AOLT,并将其分为对照组(C-R)、假手术组和乌司他丁治疗组。通过检测病理性肾损伤、炎症标志物和氧化应激指标,探讨乌司他丁对阿基的影响及其可能机制。临床试验显示,应用乌司他丁可降低肝奥尔特后阿基的发生率(P<0.05),并降低奥尔特24 h内血清胱抑素C和尿β2微球蛋白水平(P<0.05)。乌司他丁能显著缩短患者在重症监护室的时间(与C组相比P<0.01)、通气时间和血液透析率(与C组相比P<0.05),从而显著改善患者的恢复。在大鼠AOLT模型中,乌司他丁应用还显示通过降低血清胱抑素C和肌酐水平来减轻肾脏病理损伤。与C-R组相比,乌司他丁组肿瘤坏死因子-α、白细胞介素-6、过氧化氢和活性氧水平明显降低,超氧化物歧化酶水平明显升高(P<0.05)。总之,乌司他丁应用被证明通过抑制炎症和氧化来防止奥尔特后的阿基。
Acute kidney injury (AKI) is a common complication following orthotopic liver transplantation (OLT) that evidently affects prognosis. However, no effective treatment exists for AKI. The aim of the present study was to elucidate whether ulinastatin application during OLT in humans can reduce kidney damage and improve renal function. In addition, the underlying mechanisms of ulinastatin were investigated on a rat autologous OLT (AOLT) model. In total, 60 patients undergoing an OLT were randomly selected to receive ulinastatin (U group; n=30) or saline (C group; n=30) during the OLT surgery. The patient demographics, AKI incidence rate, recovery indicators and renal injury indexes were measured during the perioperative period. In addition to the clinical trials, 40 rats were subjected to an AOLT and were divided into the control (C-R), sham-operation and ulinastatin treatment groups. Pathological renal damage, biomarkers of inflammation and oxidative stress were measured to investigate the effects and possible mechanisms of ulinastatin on AKI. In the clinical trials, ulinastatin application was shown to attenuate the incidence of AKI following OLT (P<0.05) and reduce the serum levels of cystatin C and urinary β2 microglobulin within 24 h of the OLT (P<0.05). Furthermore, ulinastatin was found to significantly improve the recovery of patients by reducing the time spent in the intensive care unit (P<0.01 vs. C group), the ventilation time and the hemodialysis rates (P<0.05 vs. C group). In the rat AOLT model, ulinastatin application was also shown to relieve renal pathological damage by reducing the serum cystatin C and creatinine levels. Notably, the levels of tumor necrosis factor-α, interleukin-6, hydrogen peroxide and reactive oxygen species were evidently reduced, while the level of superoxide dismutase was increased in the ulinastatin groups (P<0.05, vs. C-R group). In conclusion, ulinastatin application was demonstrated to protect against AKI following OLT by inhibiting inflammation and oxidation.
DOI: 10.1186/1471-227x-13-s1-s7
发表时间: 2013
影响因子: 2.5
作者:
Song Z;Chen G;Lin G;Jia C;Cao J;Ao G
通讯作者: Ao G
DOI: 10.3892/ol.2013.1576
发表时间: 2013-11
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期刊: BMC nephrology
影响因子: 2.3
作者:
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发表时间: 2013-11
影响因子: 3.6
作者:
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通讯作者: Dent P
乌司他丁通过 mTOR 激活调节自噬,保护心肌细胞免受缺血再灌注损伤
DOI: 10.3892/mmr.2014.2450
发表时间: 2014-10-01
影响因子: 3.4
作者:
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通讯作者: Wang, Zhinong