Alaca Nuray, Özbeyli Dilek, Uslu Serap, Şahin Hasan Hüseyin, Yiğittürk Gürkan, Kurtel Hızır, Öktem Gülperi, Çağlayan Yeğen Berrak
Department of Physiotherapy and Rehabilitation, Acıbadem University Faculty of Health Sciences, İstanbul, Turkey.
Turk J Gastroenterol. 2017 Nov;28(6):476-484. doi: 10.5152/tjg.2017.16742. Epub 2017 Oct 25.
BACKGROUND/AIMS: Cholestasis, which results in hepatic cell death, fibrosis, cirrhosis, and eventually liver failure, is associated with oxidative stress. The aim of this study was to evaluate the effects of milk thistle (MT, Silybum marianum) and ursodeoxycholic acid (UDCA) or their combination on the activation of hepatic stem cells and on the severity of cholestasis liver injury in rats.
Under anesthesia, bile ducts of female Sprague Dawley rats were ligated (BDL) or had sham operation. BDL rats were administered saline, UDCA (15 mg/kg/d), MT (600 mg/kg/d), or UDCA+MT by gavage for 10 days. On the 11th day, rats were sacrificed and blood and liver samples were obtained. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) levels, and myeloperoxidase (MPO) activity were measured. Hepatic injury, a-smooth muscle actin expression, and stem cell markers c-kit, c-Myc, Oct3/4, and SSEA-1 were histologically determined.
Histological scores, serum ALT, and hepatic MDA levels were higher in BDL group than in the sham rats, while all treatments significantly reduced these levels. The reduction in ALT was significantly greater in UCDA+MT-treated group than in other treatment groups. c-Kit, c-Myc, Oct3/4, and SSEA-1 were increased in saline-treated BDL group with respect to sham-operated control group, and these markers were significantly reduced in all treatment groups.
In addition to a modulatory effect on the stem cell-induced regenerative response of the liver, UDCA, MT, and their combination demonstrated similar anti-inflammatory and antiproliferative effects on cholestasis-induced hepatic injury.
背景/目的：胆汁淤积会导致肝细胞死亡、纤维化、肝硬化，并最终引发肝衰竭，且与氧化应激相关。本研究旨在评估水飞蓟（MT，水飞蓟属植物）和熊去氧胆酸（UDCA）或它们的组合对大鼠肝干细胞激活及胆汁淤积性肝损伤严重程度的影响。
在麻醉状态下，对雌性斯普拉格-道利大鼠进行胆管结扎（BDL）或假手术。BDL大鼠通过灌胃给予生理盐水、UDCA（15毫克/千克/天）、MT（600毫克/千克/天）或UDCA+MT，持续10天。在第11天，处死大鼠并获取血液和肝脏样本。测量血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、肝脏丙二醛（MDA）水平以及髓过氧化物酶（MPO）活性。通过组织学方法确定肝损伤、α-平滑肌肌动蛋白表达以及干细胞标志物c-kit、c-Myc、Oct3/4和SSEA-1。
BDL组的组织学评分、血清ALT和肝脏MDA水平高于假手术大鼠，而所有治疗均显著降低了这些水平。UDCA+MT治疗组的ALT降低幅度显著大于其他治疗组。与假手术对照组相比，生理盐水处理的BDL组中c-Kit、c-Myc、Oct3/4和SSEA-1升高，而所有治疗组中这些标志物均显著降低。
除了对肝干细胞诱导的肝脏再生反应具有调节作用外，UDCA、MT及其组合对胆汁淤积诱导的肝损伤表现出相似的抗炎和抗增殖作用。
