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百里醌可逆转与实验性甲状腺功能减退相关的非酒精性脂肪性肝病(NAFLD)。

Thymoquinone reverses nonalcoholic fatty liver disease (NAFLD) associated with experimental hypothyroidism.

作者信息

Ayuob Nasra Naeim, Abdel-Hamid Ahmed Abdel Hamid Mohamed, Helal Ghada Mohamed Moneir, Mubarak Wafaa Alaa

机构信息

Department of Histology, Faculty of Medicine, Mansoura University, Egypt;

出版信息

Rom J Morphol Embryol. 2019;60(2):479-486.

PMID:31658321
Abstract

OBJECTIVES

To assess the efficacy of thymoquinone (TQ), the most active constituent in Nigella sativa, which is a medicinal plant from the Ranunculaceae family, in restoring the normal liver structure after 6-propyl-2-thiouracil (PTU)-induced hypothyroidism and explore the mechanism behind this.

MATERIALS AND METHODS

Hypothyroidism was induced in rats by injection of PTU [6 mg∕kg body weight (b.w.)] for six weeks. Twenty-four adult male Wistar rats were divided into four groups; the control, TQ-treated at the dose 400 mg∕kg b.w., untreated hypothyroidism and TQ-treated hypothyroid groups. Serum levels of thyroid hormones and antioxidant profile were measured. Real-time polymerase chain reaction was used to assess gene expression of catalase (CAT). Liver was histopathologically examined using routine and immunohistochemical techniques.

RESULTS

Livers of rats with hypothyroidism displayed nonalcoholic fatty liver disease (NAFLD) in the form of steatosis as well as nonalcoholic steatohepatitis (NASH). Moreover, there was an intralobular inflammatory reaction associated with significant (p<0.05) increases in the density of resident hepatic macrophages [cluster of differentiation 68 (CD68)+ cells], as well as in activated hepatic stellate cells, alpha-smooth muscle actin (α-SMA) index in livers with hypothyroidism. Resolution of hypothyroid NAFLD was observed in livers after treatment with TQ. The significantly increased (p<0.05) steatosis, lobular inflammation, NAFLD activity scores, α-SMA index as well as CD68+ cells induced by hypothyroidism were corrected after TQ administration. Up-regulation of the CAT gene in livers with hypothyroidism after treatment with TQ supported our hypothesis of its antioxidant mechanistic hepatoprotective action.

CONCLUSIONS

TQ efficiently restores the normal liver histology in hypothyroid rats with up-regulation of the antioxidant CAT gene.

摘要

目的

评估黑种草(毛茛科药用植物)中最具活性的成分百里醌(TQ)在恢复6-丙基-2-硫氧嘧啶(PTU)诱导的甲状腺功能减退后正常肝脏结构方面的疗效,并探究其背后的机制。

材料与方法

通过注射PTU[6毫克/千克体重(b.w.)]诱导大鼠甲状腺功能减退6周。将24只成年雄性Wistar大鼠分为四组;对照组、以400毫克/千克b.w.剂量进行TQ治疗组、未经治疗的甲状腺功能减退组和TQ治疗的甲状腺功能减退组。检测血清甲状腺激素水平和抗氧化指标。采用实时聚合酶链反应评估过氧化氢酶(CAT)基因表达。使用常规和免疫组织化学技术对肝脏进行组织病理学检查。

结果

甲状腺功能减退大鼠的肝脏呈现非酒精性脂肪性肝病(NAFLD),表现为脂肪变性以及非酒精性脂肪性肝炎(NASH)。此外,存在小叶内炎症反应,甲状腺功能减退肝脏中的驻留肝巨噬细胞[分化簇68(CD68)+细胞]密度以及活化的肝星状细胞、α-平滑肌肌动蛋白(α-SMA)指数显著(p<0.05)增加。TQ治疗后,甲状腺功能减退的NAFLD在肝脏中得到缓解。TQ给药后,甲状腺功能减退诱导的显著增加(p<0.05)的脂肪变性、小叶炎症、NAFLD活动评分、α-SMA指数以及CD68+细胞均得到纠正。TQ治疗后甲状腺功能减退肝脏中CAT基因的上调支持了我们关于其抗氧化机制性肝保护作用的假设。

结论

TQ通过上调抗氧化CAT基因有效地恢复了甲状腺功能减退大鼠的正常肝脏组织学。

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