硫代葡萄糖苷代谢产物可改善胆管结扎大鼠门静脉高压和肝硬化的发展。

Glucobrassicin Metabolites Ameliorate the Development of Portal Hypertension and Cirrhosis in Bile Duct-Ligated Rats.

机构信息

Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan.

出版信息

Int J Mol Sci. 2019 Aug 26;20(17):4161. doi: 10.3390/ijms20174161.

Abstract

Patients suffering from liver cirrhosis are often complicated with the formation of portosystemic collateral vessels, which is associated with the progression of a splanchnic hyperdynamic circulatory state. Alleviating pathological angiogenesis has thus been proposed to be a feasible treatment strategy. Indole-3-carbinol (C9H9NO, I3C) and 3,3'-diindolymethane (DIM), formed by the breakdown of glucosinolate glucobrassicin, are prevalent in cruciferous vegetables and have anti-angiogenesis properties. We aimed to evaluate their influences on portal hypertension, the severity of mesenteric angiogenesis, and portosystemic collaterals in cirrhosis. Sprague-Dawley rats with common bile duct ligation (CBDL)-induced liver cirrhosis or sham operation (surgical control) were randomly allocated to receive I3C (20 mg/kg/3 day), DIM (5 mg/kg/day) or vehicle for 28 days. The systemic and portal hemodynamics, severity of portosystemic shunting, mesenteric angiogenesis, and mesenteric proangiogenic factors protein expressions were evaluated. Compared to vehicle, both DIM and I3C significantly reduced portal pressure, ameliorated liver fibrosis, and down-regulated mesenteric protein expressions of vascular endothelial growth factor and phosphorylated Akt. DIM significantly down-regulated pErk, and I3C down-regulated NFκB, pIκBα protein expressions, and reduced portosystemic shunting degree. The cruciferous vegetable byproducts I3C and DIM not only exerted a portal hypotensive effect but also ameliorated abnormal angiogenesis and portosystemic collaterals in cirrhotic rats.

摘要

患有肝硬化的患者常伴有门体侧支循环的形成,这与内脏高动力循环状态的进展有关。因此,减轻病理性血管生成被认为是一种可行的治疗策略。吲哚-3-甲醇(C9H9NO,I3C)和 3,3'-二吲哚甲烷(DIM)是由硫代葡萄糖苷葡萄糖异硫氰酸盐分解形成的,存在于十字花科蔬菜中,具有抗血管生成特性。我们旨在评估它们对肝硬化门静脉高压、肠系膜血管生成严重程度和门体侧支循环的影响。采用胆总管结扎(CBDL)诱导的肝硬化或假手术(手术对照)大鼠随机分为接受 I3C(20mg/kg/3 天)、DIM(5mg/kg/天)或载体 28 天。评估系统和门脉血液动力学、门体分流严重程度、肠系膜血管生成和肠系膜促血管生成因子蛋白表达。与载体相比,DIM 和 I3C 均显著降低门静脉压力,改善肝纤维化,并下调肠系膜血管内皮生长因子和磷酸化 Akt 的蛋白表达。DIM 显著下调 pErk,I3C 下调 NFκB、pIκBα 蛋白表达,并降低门体分流程度。十字花科蔬菜副产物 I3C 和 DIM 不仅具有降压作用,而且改善了肝硬化大鼠异常的血管生成和门体侧支循环。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/6747388/ac85c7731a1d/ijms-20-04161-g001a.jpg

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