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N-乙酰半胱氨酸和阿托伐他汀对大鼠肠缺血再灌注模型肾肝损伤的保护作用。

Protective effects of N-acetylcystein and atorvastatin against renal and hepatic injury in a rat model of intestinal ischemia-reperfusion.

机构信息

Laboratory for Experimental Surgery and Surgical Research "N.S Christeas", Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Laboratory for Experimental Surgery and Surgical Research "N.S Christeas", Medical School, National and Kapodistrian University of Athens, Athens, Greece.

出版信息

Biomed Pharmacother. 2017 May;89:673-680. doi: 10.1016/j.biopha.2017.02.086. Epub 2017 Mar 6.

Abstract

AIM OF THE STUDY

We sought to examine whether the separate and combined effect of N-acetylcystein (NAC) and atorvastatin prevented hepatic and renal tissue injury induced by intestinal ischemia-reperfusion (I/R).

MATERIAL AND METHODS

40 male Wistar rats were allocated into 5 experimental groups; Control (n=8): sham, I/R (n=8): rats underwent occlusion of superior mesenteric artery for 45min, Atorvastatin (n=8): rats received 10mg/kg atorvastatin, NAC (n=8): rats received 160mg/kg NAC, NAC&Atorvastatin (n=8): rats received both aforementioned agents. Administration of the agents was facilitated by oral gavage 24h before I/R. Serum levels of urea, creatinine, transaminases, IL-1β, IL-6, TNF-α, ICAM-1, as well as liver and kidney histopathological examination were evaluated.

RESULTS

Pretreatment with either NAC or Atorvastatin or their combination led to lower levels of transaminases and ICAM-1 (2.75±0.46, 2.88±0.84 and 1.5±0.76 respectively for NAC, Atorvastatin and I/R groups), while only their combination led to lower ratios of IL-1, IL-6 and TNF-α than I/R group (1.3±0.12 vs 1.94±0.54, 1.21±0.11 vs 2.12±0.96 and 1.33±0.11 vs 2.14±0.77, respectively). NAC was associated with enhanced renal tissue histology, while atorvastatin was found superior in protecting hepatic tissue degenaration.

CONCLUSIONS

Both agents, seperately and combined, seem to exhibited tissue-specific protective activity against intestinal I/R induced injury.

摘要

目的

本研究旨在探讨 N-乙酰半胱氨酸(NAC)和阿托伐他汀的单独和联合作用是否能预防肠缺血再灌注(I/R)引起的肝肾功能损伤。

材料与方法

将 40 只雄性 Wistar 大鼠随机分为 5 个实验组;对照组(n=8):假手术组;I/R 组(n=8):大鼠肠系膜上动脉夹闭 45min;阿托伐他汀组(n=8):大鼠给予 10mg/kg 阿托伐他汀;NAC 组(n=8):大鼠给予 160mg/kg NAC;NAC 和阿托伐他汀组(n=8):大鼠给予上述两种药物。在 I/R 前 24 小时,通过口服灌胃给予药物。评估血清尿素、肌酐、转氨酶、IL-1β、IL-6、TNF-α、ICAM-1 水平以及肝肾功能组织学检查。

结果

NAC 或阿托伐他汀或两者联合预处理可降低转氨酶和 ICAM-1 水平(NAC、阿托伐他汀和 I/R 组分别为 2.75±0.46、2.88±0.84 和 1.5±0.76),只有联合治疗可降低 IL-1、IL-6 和 TNF-α 比值(分别为 1.3±0.12 与 1.94±0.54、1.21±0.11 与 2.12±0.96 和 1.33±0.11 与 2.14±0.77)。NAC 与改善肾组织病理学相关,而阿托伐他汀在保护肝组织变性方面表现更佳。

结论

两种药物,单独或联合使用,对肠 I/R 诱导的损伤均表现出组织特异性保护活性。

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