关键词: TGF‐ß1 astaxanthin bile duct ligation liver fibrosis α‐SMA

Mesh : Animals Xanthophylls / pharmacology therapeutic use Male Rats, Wistar Rats Cholestasis / pathology metabolism drug therapy Liver Cirrhosis / metabolism pathology drug therapy prevention & control Ligation Bile Ducts / surgery Liver / drug effects pathology metabolism Transforming Growth Factor beta1 / metabolism

来  源:   DOI:10.1002/jbt.23788

Abstract:
In this study, we evaluated the hepatoprotective effects of astaxanthin, a natural carotenoid, against the cholestatic liver fibrosis induced by bile duct ligation (BDL). Toward this end, male rats were subjected to BDL and treated with astaxanthin for 35 days. Afterwards, their serum and liver biochemical factors were assessed. Also, histopathological and immunohistochemical analyses were performed to determine the fibrosis and the expression levels of alpha-smooth muscle actin (α-SMA) and transforming growth factor beta (TGF-ß1) in the liver tissue. Based on the results, BDL caused a significant increase in liver enzyme levels, blood lipids, and bilirubin, while decreasing the activity of superoxide dismutase(SOD), catalase (CAT), and glutathione (GSH) enzymes. Also, in the BDL rats, hepatocyte necrosis, infiltration of inflammatory lymphocytes, and hyperplasia of bile ducts were detected, along with a significant increase in α-SMA and TGF-ß1 expression. Astaxanthin, however, significantly prevented the BDL\'s detrimental effects. In all, 10 mg/kg of this drug maintained the bilirubin and cholesterol serum levels of BDL rats at normal levels. It also reduced the liver enzymes\' activity and serum lipids, while increasing the SOD, CAT, and GSH activity in BDL rats. The expression of α-SMA and TGF-ß1 in the BDL rats treated with 10 mg/kg of astaxanthin was moderate (in 34%-66% of cells) and no considerable cholestatic fibrosis was observed in this group. However, administrating the 20 mg/kg of astaxanthin was not effective in this regard. These findings showed that astaxanthin could considerably protect the liver from cholestatic damage by improving the biochemical features and regulating the expression of related proteins.
摘要:
在这项研究中,我们评估了虾青素的保肝作用,一种天然的类胡萝卜素,抗胆管结扎(BDL)引起的胆汁淤积性肝纤维化。为此,对雄性大鼠进行BDL并用虾青素处理35天。之后,对其血清和肝脏生化因子进行评估.此外,进行组织病理学和免疫组织化学分析以确定肝组织中的纤维化以及α-平滑肌肌动蛋白(α-SMA)和转化生长因子β(TGF-β1)的表达水平。根据结果,BDL引起肝酶水平显著升高,血脂,和胆红素,同时降低超氧化物歧化酶(SOD)的活性,过氧化氢酶(CAT),和谷胱甘肽(GSH)酶。此外,在BDL大鼠中,肝细胞坏死,炎性淋巴细胞浸润,并检测到胆管增生,随着α-SMA和TGF-β1表达的显着增加。虾青素,然而,显著防止了BDL的有害影响。总之,10mg/kg该药使BDL大鼠血清胆红素和胆固醇水平维持在正常水平。它还降低肝酶活性和血清脂质,在增加SOD的同时,CAT,和BDL大鼠的GSH活性。用10mg/kg虾青素处理的BDL大鼠中α-SMA和TGF-β1的表达是中等的(在34%-66%的细胞中),在该组中未观察到明显的胆汁淤积性纤维化。然而,服用20mg/kg的虾青素在这方面无效。这些发现表明虾青素可以通过改善生化特征和调节相关蛋白的表达来显著保护肝脏免受胆汁淤积性损伤。
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