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改性柑橘果胶通过抑制半乳糖凝集素-3和诱导星状细胞凋亡来阻止肝纤维化的进展。

Modified citrus pectin stops progression of liver fibrosis by inhibiting galectin-3 and inducing apoptosis of stellate cells.

作者信息

Abu-Elsaad Nashwa M, Elkashef Wagdi Fawzi

机构信息

a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Adakahlia 35516, Egypt.

b Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.

出版信息

Can J Physiol Pharmacol. 2016 May;94(5):554-62. doi: 10.1139/cjpp-2015-0284. Epub 2015 Dec 16.

DOI:10.1139/cjpp-2015-0284
PMID:27010252
Abstract

Modified citrus pectin (MCP) is a pH modified form of the dietary soluble citrus peel fiber known as pectin. The current study aims at testing its effect on liver fibrosis progression. Rats were injected with CCl4 (1 mL/kg, 40% v/v, i.p., twice a week for 8 weeks). Concurrently, MCP (400 or 1200 mg/kg) was administered daily in drinking water from the first week in groups I and II (prophylactic model) and in the beginning of week 5 in groups III and IV (therapeutic model). Liver function biomarkers (ATL, AST, and ALP), fibrosis markers (laminin and hyaluronic acid), and antioxidant biomarkers (reduced glutathione (GSH) and superoxide dismutase (SOD)) were measured. Stained liver sections were scored for fibrosis and necroinflammation. Additionally, expression of galectin-3 (Gal-3), α-smooth muscle actin (SMA), tissue inhibitor metalloproteinase (TIMP)-1, collagen (Col)1A1, caspase (Cas)-3, and apoptosis related factor (FAS) were assigned. Modified pectin late administration significantly (p < 0.05) decreased malondialdehyde (MDA), TIMP-1, Col1A1, α-SMA, and Gal-3 levels and increased levels of FAS, Cas-3, GSH, and SOD. It also decreased percentage of fibrosis and necroinflammation significantly (p < 0.05). It can be concluded that MCP can attenuate liver fibrosis through an antioxidant effect, inhibition of Gal-3 mediated hepatic stellate cells activation, and induction of apoptosis.

摘要

改性柑橘果胶(MCP)是膳食中可溶性柑橘皮纤维果胶的一种pH改性形式。本研究旨在测试其对肝纤维化进展的影响。给大鼠注射四氯化碳(1 mL/kg,40% v/v,腹腔注射,每周两次,共8周)。同时,在第I组和第II组(预防模型)从第一周开始以及在第III组和第IV组(治疗模型)在第5周开始,每天在饮用水中给予MCP(400或1200 mg/kg)。测量肝功能生物标志物(谷丙转氨酶、谷草转氨酶和碱性磷酸酶)、纤维化标志物(层粘连蛋白和透明质酸)以及抗氧化生物标志物(还原型谷胱甘肽(GSH)和超氧化物歧化酶(SOD))。对肝脏切片进行纤维化和坏死性炎症评分。此外,还检测了半乳糖凝集素-3(Gal-3)、α-平滑肌肌动蛋白(SMA)、组织金属蛋白酶抑制剂(TIMP)-1、胶原蛋白(Col)1A1、半胱天冬酶(Cas)-3和凋亡相关因子(FAS)的表达。晚期给予改性果胶显著(p < 0.05)降低了丙二醛(MDA)、TIMP-1、Col1A1、α-SMA和Gal-3的水平,并提高了FAS、Cas-3、GSH和SOD的水平。它还显著降低了纤维化和坏死性炎症的百分比(p < 0.05)。可以得出结论,MCP可通过抗氧化作用、抑制Gal-3介导的肝星状细胞活化以及诱导凋亡来减轻肝纤维化。

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