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龙生蛭胶囊通过改善肝脏脂质代谢和抑制炎症减轻载脂蛋白 E 缺陷小鼠的动脉粥样硬化病变。

LongShengZhi Capsule Reduces Established Atherosclerotic Lesions in apoE-Deficient Mice by Ameliorating Hepatic Lipid Metabolism and Inhibiting Inflammation.

机构信息

College of Life Sciences, Key Laboratory of Bioactive Materials of Ministry of Education, Nankai University, Tianjin, China.

College of Biomedical Engineering, Hefei University of Technology, Hefei, China.

出版信息

J Cardiovasc Pharmacol. 2019 Feb;73(2):105-117. doi: 10.1097/FJC.0000000000000642.

DOI:10.1097/FJC.0000000000000642
PMID:30540683
Abstract

Disorders of lipid metabolism and inflammation play an important role in atherosclerosis. LongShengZhi (LSZ) capsule, a Chinese herbal medicine, has been used for treatment of patients with vascular diseases for many years. In this article, we determined the effect of LSZ on the progression of established atherosclerotic lesions in apoE-deficient (apoE) mice. ApoE mice were prefed high-fat diet (HFD) for 8 weeks to induce atherosclerosis, then started with LSZ treatment contained in HFD for 10 weeks. Although LSZ had little effect on HFD-induced hypercholesterolemia, it substantially reduced en face and sinus aortic lesions. The reduction of lesions was associated with reduced macrophage/foam cell accumulation by activating ABCA1/ABCG1 expression. LSZ maintained the integrity of arterial wall by increasing collagen or smooth muscle cell content and inhibiting cell apoptosis. LSZ also attenuated HFD-induced fatty liver by down-regulating expression of lipogenic and cholesterol synthetic genes while activating expression of triglyceride catabolism genes. Moreover, LSZ demonstrated potent anti-inflammatory effects. In vivo, LSZ reduced serum TNF-α levels, infiltration of neutrophils, Kupffer cells, and expression of inflammatory cytokines in the liver. In vitro, it inhibited lipopolysaccharide or palmitate-induced expression of inflammatory cytokines in macrophages. Therefore, LSZ reduces atherosclerosis by ameliorating hepatic lipid metabolism and inhibiting inflammation.

摘要

脂质代谢和炎症紊乱在动脉粥样硬化中起着重要作用。LongShengZhi(LSZ)胶囊是一种中药,多年来一直用于治疗血管疾病患者。在本文中,我们确定了 LSZ 对载脂蛋白 E 缺陷(apoE)小鼠已建立的动脉粥样硬化病变进展的影响。apoE 小鼠先用高脂肪饮食(HFD)喂养 8 周以诱导动脉粥样硬化,然后开始用 HFD 中的 LSZ 治疗 10 周。尽管 LSZ 对 HFD 诱导的高胆固醇血症几乎没有影响,但它大大减少了主动脉面和窦状动脉病变。病变的减少与通过激活 ABCA1/ABCG1 表达来减少巨噬细胞/泡沫细胞积累有关。LSZ 通过增加胶原蛋白或平滑肌细胞含量和抑制细胞凋亡来维持动脉壁的完整性。LSZ 还通过下调脂肪生成和胆固醇合成基因的表达,同时激活甘油三酯分解代谢基因的表达,减轻 HFD 诱导的脂肪肝。此外,LSZ 具有强大的抗炎作用。在体内,LSZ 降低了血清 TNF-α 水平、中性粒细胞、库普弗细胞的浸润以及肝脏中炎症细胞因子的表达。在体外,它抑制了巨噬细胞中脂多糖或棕榈酸诱导的炎症细胞因子的表达。因此,LSZ 通过改善肝脏脂质代谢和抑制炎症来减少动脉粥样硬化。

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