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托吡酯改善大鼠腹主动脉夹闭所致的肝损伤。

Topiramate ameliorates abdominal aorta cross-clamping induced liver injury in rats.

作者信息

Cure Erkan, Cure Medine C, Tumkaya Levent, Kalkan Yildiray, Aydin Ibrahim, Kirbas Aynur, Yilmaz Arif, Yuce Suleyman, Gokce Mehmet F

机构信息

Department of Internal Medicine, Recep Tayyip Erdogan University, School of Medicine, Rize, Turkey.

出版信息

Saudi J Gastroenterol. 2014 Sep-Oct;20(5):297-303. doi: 10.4103/1319-3767.141690.

Abstract

BACKGROUND AND AIM

Ischemia/reperfusion (I/R) injury in the liver occurs after a prolonged period of ischemia followed by restoration of hepatic blood perfusion. During the surgery of abdominal aorta, I/R injury causes damage to lower extremities and many organs, especially liver. The antioxidant and tumor necrosis factor-alpha (TNF-α) suppression effects of topiramate (TPM) have been reported in several studies. We evaluated the potential protective effect of TPM on cellular damage in liver tissue during I/R injury.

MATERIALS AND METHODS

Thirty male Wistar albino rats were divided into three groups: Control, I/R, and I/R plus TPM (I/R + TPM) groups. Laparotomy without I/R injury was performed in the control group. After laparotomy, cross-ligation of infrarenal abdominal aorta was applied for 2 h in I/R groups that was followed by 2 h of reperfusion. TPM (100 mg/kg/day) was orally administrated to the animals in the I/R + TPM group for seven consecutive days before I/R procedure.

RESULTS

The I/R group's TNF-α and interleukin-6 (IL-6) levels were significantly higher than those of the control (P = 0.010; P = 0.002) and I/R + TPM groups (P = 0.010; P = 0.002, respectively). Asymmetric dimethyl arginine (ADMA) levels of I/R group were higher than the control (P = 0.015) and I/R + TPM groups. I/R caused serious histopathological damage to liver tissue; however, TPM led to very low histopathological changes.

CONCLUSION

Our data demonstrated that TPM treatment prominently decreases the severity of liver I/R injury. TPM pretreatment may have preventive effects on liver injury via I/R during intra-abdominal surgery.

摘要

背景与目的

肝脏缺血/再灌注(I/R)损伤发生于长时间缺血后肝血流灌注得以恢复之时。在腹主动脉手术过程中,I/R损伤会对下肢及许多器官造成损害,尤其是肝脏。多项研究报道了托吡酯(TPM)的抗氧化及肿瘤坏死因子-α(TNF-α)抑制作用。我们评估了TPM对I/R损伤期间肝组织细胞损伤的潜在保护作用。

材料与方法

30只雄性Wistar白化大鼠被分为三组:对照组、I/R组和I/R加TPM(I/R + TPM)组。对照组进行无I/R损伤的剖腹手术。剖腹手术后,I/R组行肾下腹主动脉交叉结扎2小时,随后再灌注2小时。在I/R手术前,I/R + TPM组动物连续7天口服TPM(100 mg/kg/天)。

结果

I/R组的TNF-α和白细胞介素-6(IL-6)水平显著高于对照组(P = 0.010;P = 0.002)和I/R + TPM组(分别为P = 0.010;P = 0.002)。I/R组的不对称二甲基精氨酸(ADMA)水平高于对照组(P = 0.015)和I/R + TPM组。I/R对肝组织造成了严重的组织病理学损伤;然而,TPM导致的组织病理学变化非常轻微。

结论

我们的数据表明,TPM治疗可显著降低肝脏I/R损伤的严重程度。TPM预处理可能对腹部手术期间因I/R引起的肝损伤具有预防作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe35/4196345/8d23b3846668/SJG-20-297-g002.jpg

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