腹腔注射褪黑素对大鼠模型中因杀头节剂溶液所致腐蚀性硬化性胆管炎的影响。

Effects of intraperitoneal melatonin on caustic sclerosing cholangitis due to scolicidal solution in a rat model.

作者信息

Sezer Atakan, Hatipoglu Ahmet Rahmi, Usta Ufuk, Altun Gülay, Sut Necdet

机构信息

Department of General Surgery, Faculty of Medicine, Trakya University, Edirne, Turkey.

Department of Pathology, Faculty of Medicine, Trakya University, Edirne, Turkey.

出版信息

Curr Ther Res Clin Exp. 2010 Apr;71(2):118-28. doi: 10.1016/j.curtheres.2010.03.004.

DOI:10.1016/j.curtheres.2010.03.004

PMID:24683258

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3967282/

Abstract

BACKGROUND

Hydatid disease is a worldwide health problem. Treatment is surgical or percutaneous, using scolicidal agents. Caustic sclerosing cholangitis might develop after the contact of scolicidal agents with the biliary ducts. Melatonin, an antioxidant, anti-inflammatory, and anticarcinogenic agent, might be used in the treatment of caustic sclerosing cholangitis due to its possible preventive effects on fibrosis and cell damage.

OBJECTIVE

The aim of the study was to investigate the effects of melatonin on an experimentally developed caustic sclerosing cholangitis with scolicidal solution (formalin) in a rat model.

METHODS

Forty female Sprague-Dawley rats aged 11 to 13 weeks and weighing 250 ± 30 g were randomly assigned to 1 of 4 groups of 10: formalin 5% at 0.5 mL/d + melatonin placebo; formalin placebo + intraperitoneal melatonin 10 mg/kg/d; formalin 5% at 0.5 mL/d + melatonin 10 mg/kg/d; and formalin placebo and melatonin placebo (control). Hepatobiliary function was assessed using dynamic scintigraphy with technetium-99m-mebrofenin on study day 60. The histology of the liver and biliary duct specimens was examined on study day 60. In each group, histopathologic alterations were scored as absent, slight, mild, or severe.

RESULTS

Mean severity scores for parenchymal necrosis in the liver (P < 0.01), portal fibrosis (P < 0.01), biliary duct proliferation (P < 0.001), cholangitis/ pericholangitis (P < 0.01), hyperemia in the biliary ducts (P < 0.01), and fibrosis (P < 0.01) were significantly lower in rats treated with formalin + melatonin compared with those treated with formalin alone. No significant differences were observed between the 3 treatment groups with respect to t½, a parameter used to assess the secretion function of the hepatocytes. However, the t½ was significantly longer in the treatment groups compared with controls (P < 0.001).

CONCLUSION

In this experimental study in a rat model of caustic sclerosing cholangitis, the histopathologic and scintigraphic findings suggested that melatonin is effective in attenuating the damage caused by scolicidal agents on the liver and biliary ducts.

摘要

背景

包虫病是一个全球性的健康问题。治疗方法为手术治疗或经皮治疗，使用杀头节剂。杀头节剂与胆管接触后可能会引发腐蚀性硬化性胆管炎。褪黑素是一种抗氧化、抗炎和抗癌剂，由于其对纤维化和细胞损伤可能具有预防作用，或许可用于治疗腐蚀性硬化性胆管炎。

目的

本研究旨在探讨褪黑素对大鼠模型中用杀头节剂溶液（福尔马林）实验性诱发的腐蚀性硬化性胆管炎的影响。

方法

将40只11至13周龄、体重250±30 g的雌性Sprague-Dawley大鼠随机分为4组，每组10只：5%福尔马林0.5 mL/d + 褪黑素安慰剂；福尔马林安慰剂 + 腹腔注射褪黑素10 mg/kg/d；5%福尔马林0.5 mL/d + 褪黑素10 mg/kg/d；以及福尔马林安慰剂和褪黑素安慰剂（对照组）。在研究第60天，使用锝-99m-美布芬宁动态闪烁扫描评估肝胆功能。在研究第60天检查肝脏和胆管标本的组织学。对每组的组织病理学改变进行评分，分为无、轻度、中度或重度。

结果

与单独使用福尔马林治疗的大鼠相比，用福尔马林 + 褪黑素治疗的大鼠肝脏实质坏死（P < 0.01）、门脉纤维化（P < 0.01）、胆管增生（P < 0.001）、胆管炎/胆管周围炎（P < 0.01）、胆管充血（P < 0.01）和纤维化（P < 0.01）的平均严重程度评分显著更低。在3个治疗组之间，关于评估肝细胞分泌功能的参数t½未观察到显著差异。然而，治疗组的t½显著长于对照组（P < 0.001）。