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口服西洛他唑可提高大鼠肝脏缺血/再灌注损伤后的生存率。

Oral administration of cilostazol improves survival rate after rat liver ischemia/reperfusion injury.

作者信息

Fujii Taku, Obara Hideaki, Matsubara Kentaro, Fujimura Naoki, Yagi Hiroshi, Hibi Taizo, Abe Yuta, Kitago Minoru, Shinoda Masahiro, Itano Osamu, Tanabe Minoru, Masugi Yohei, Sakamoto Michiie, Kitagawa Yuko

机构信息

Department of Surgery, Hiratsuka City Hospital, Kanagawa, Japan.

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

出版信息

J Surg Res. 2017 Jun 1;213:207-214. doi: 10.1016/j.jss.2017.02.020. Epub 2017 Feb 23.

DOI:10.1016/j.jss.2017.02.020
PMID:28601316
Abstract

BACKGROUND

Cilostazol is a type III phosphodiesterase inhibitor used to treat the symptoms of intermittent claudication. Recent studies have shown that cilostazol decreases ischemia/reperfusion (I/R) injury in several organs.

MATERIALS AND METHODS

We evaluated the effects of cilostazol in a rat model of liver I/R injury. Thirty male Wistar rats with liver I/R injury were divided into a cilostazol or saline (control) group (n = 15 each). Each rat was orally administered cilostazol or saline for 3 d before I/R injury. Liver I/R injury was induced via 1 h of warm ischemia of the median and left lateral liver lobes, followed by 3 h of reperfusion. The rats were then euthanized. Serum aspartate aminotransferase, alanine aminotransferase, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels were measured. The Mann-Whitney U test was used to compare the differences between the treatment groups. Histologic examination was performed on the liver tissues. We also conducted a survival study to confirm the effect of cilostazol on the mortality rate in rats. For the survival study, a liver I/R injury model with an ischemia time of 1.5 h was used, and the rats were observed for 1 wk.

RESULTS

Serum aspartate aminotransferase, alanine aminotransferase, IL-1β, and IL-6 levels were significantly lower in the cilostazol group than in the saline group. Treatment with cilostazol significantly improved pathological findings associated with liver I/R injury and increased survival rate compared to that in controls.

CONCLUSIONS

Cilostazol reduced mortality and alleviated the effects of liver I/R injury in Wistar rats.

摘要

背景

西洛他唑是一种III型磷酸二酯酶抑制剂,用于治疗间歇性跛行症状。最近的研究表明,西洛他唑可减轻多个器官的缺血/再灌注(I/R)损伤。

材料与方法

我们评估了西洛他唑在大鼠肝脏I/R损伤模型中的作用。30只雄性Wistar大鼠,造成肝脏I/R损伤后,分为西洛他唑组或生理盐水(对照)组(每组n = 15)。在I/R损伤前3天,每组大鼠分别口服西洛他唑或生理盐水。通过对肝中叶和左外叶进行1小时的热缺血,然后再灌注3小时,诱导肝脏I/R损伤。随后对大鼠实施安乐死。检测血清天冬氨酸转氨酶、丙氨酸转氨酶、白细胞介素(IL)-1β、IL-6和肿瘤坏死因子-α水平。采用Mann-Whitney U检验比较治疗组之间的差异。对肝组织进行组织学检查。我们还进行了一项生存研究,以确认西洛他唑对大鼠死亡率的影响。在生存研究中,使用缺血时间为1.5小时的肝脏I/R损伤模型,并对大鼠观察1周。

结果

西洛他唑组血清天冬氨酸转氨酶、丙氨酸转氨酶、IL-1β和IL-6水平显著低于生理盐水组。与对照组相比,西洛他唑治疗显著改善了与肝脏I/R损伤相关的病理表现,并提高了生存率。

结论

西洛他唑降低了Wistar大鼠的死亡率,并减轻了肝脏I/R损伤的影响。

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