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西罗莫司减轻大鼠肝部分缺血再灌注损伤,但损害肝再生。

Sirolimus attenuates reduced-size liver ischemia-reperfusion injury but impairs liver regeneration in rats.

机构信息

Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang Province, People's Republic of China.

出版信息

Dig Dis Sci. 2010 Aug;55(8):2255-62. doi: 10.1007/s10620-009-1002-2. Epub 2009 Oct 24.

Abstract

BACKGROUND

Evidence has suggested that immunosuppressive drugs impact ischemia-reperfusion injury.

AIMS

The purpose of the present study was to evaluate the effect of sirolimus on hepatic injury and regeneration in a rat reduced-size liver ischemia-reperfusion model.

METHODS

Using a newly developed rat reduced-size liver ischemia-reperfusion injury model, the effects of sirolimus were evaluated by assessing liver cell apoptosis and aspartate aminotransferase, myeloperoxidase, and malondialdehyde levels. In addition, liver regeneration after sirolimus treatment was evaluated by measuring liver weight resumption and by the histological examination of bromodeoxyuridine and proliferating cell nuclear antigen expression.

RESULTS

Sirolimus significantly decreased liver cell apoptosis as well as tissue myeloperoxidase and malondialdehyde levels, but impaired postischemic liver regeneration. Ischemia-reperfusion-induced elevation of aspartate aminotransferase serum levels was significantly decreased by sirolimus.

CONCLUSIONS

Despite an impairment of postischemic liver proliferation, sirolimus demonstrated beneficial amelioration of ischemia-reperfusion-induced liver injury in a reduced-size liver model in rats.

摘要

背景

有证据表明,免疫抑制剂会影响缺血再灌注损伤。

目的

本研究旨在评估西罗莫司对大鼠减小体积肝脏缺血再灌注模型中肝损伤和再生的影响。

方法

使用新开发的大鼠减小体积肝脏缺血再灌注损伤模型,通过评估肝细胞凋亡以及天门冬氨酸氨基转移酶、髓过氧化物酶和丙二醛水平来评估西罗莫司的作用。此外,通过测量肝重恢复和溴脱氧尿苷和增殖细胞核抗原表达的组织学检查来评估西罗莫司治疗后的肝再生情况。

结果

西罗莫司显著降低了肝细胞凋亡以及组织髓过氧化物酶和丙二醛水平,但损害了缺血后肝脏的再生。西罗莫司显著降低了缺血再灌注诱导的血清天门冬氨酸氨基转移酶水平升高。

结论

尽管西罗莫司抑制了缺血后肝脏的增殖,但它在大鼠减小体积肝脏模型中显示出对缺血再灌注引起的肝损伤有益的改善作用。

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