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不同左旋肉碱给药途径对载脂蛋白 E 基因敲除小鼠动脉粥样硬化发展的影响。

The Effect of Different l-Carnitine Administration Routes on the Development of Atherosclerosis in ApoE Knockout Mice.

机构信息

Tianjin First Center Hospital, Tianjin, China.

Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of PAPF, Tianjin, China.

出版信息

Mol Nutr Food Res. 2018 Mar;62(5). doi: 10.1002/mnfr.201700299. Epub 2018 Feb 5.

Abstract

SCOPE

l-Carnitine (LC) is abundant in red meat and is widely added to health supplements and food. This study focuses on the adverse effects of oral supplementation of 1.3% LC in ApoE mice and whether the parenteral administration of LC (subcutaneously, sub) has any impact on the development of atherosclerosis.

METHODS AND RESULTS

Mice are randomly divided into three groups (n = 15). All mice are fed a high-fat diet (HFD). The number of Ly6C monocytes; degree of atherosclerosis; plasma LC, γ-butyrobetaine (γBB), and trimethylamine-N-oxide (TMAO) levels; and microbial community composition are analyzed. Compared with the HFD and HFD ± LC (sub) groups, the number of Ly6C monocytes, atherosclerotic plaque area, and plasma γBB and TMAO levels are increased in the HFD ± LC (oral) group (p < 0.001). Plasma LC levels in the HFD ± LC (sub) group are higher than those in other groups. The levels of γBB, TMAO, and Ly6C monocytes are positively correlated with atherosclerotic plaque area (p < 0.01), and TMAO is positively correlated with Bacteroidetes and negatively correlated with Firmicutes at the phylum level.

CONCLUSION

In contrast with oral LC administration, subcutaneous LC administration, which bypasses its conversion to TMAO in the liver, does not have a detrimental effect on the development of atherosclerosis in male ApoE mice. Taking LC parenterally may be preferable among patients who require LC supplementation.

摘要

研究范围

左旋肉碱(LC)在红肉中含量丰富,广泛添加于保健品和食品中。本研究聚焦于口服补充 1.3%LC 对载脂蛋白 E 敲除(ApoE)小鼠的不良影响,以及 LC 的肠外给药(皮下注射,sub)是否会对动脉粥样硬化的发展产生影响。

方法和结果

将小鼠随机分为三组(n=15)。所有小鼠均喂食高脂肪饮食(HFD)。分析 Ly6C 单核细胞数量;动脉粥样硬化程度;血浆 LC、γ-丁酰甜菜碱(γBB)和三甲胺 N-氧化物(TMAO)水平;以及微生物群落组成。与 HFD 组和 HFD+LC(sub)组相比,HFD+LC(口服)组的 Ly6C 单核细胞数量、动脉粥样硬化斑块面积以及血浆 γBB 和 TMAO 水平均增加(p<0.001)。HFD+LC(sub)组的血浆 LC 水平高于其他组。γBB、TMAO 和 Ly6C 单核细胞水平与动脉粥样硬化斑块面积呈正相关(p<0.01),TMAO 与厚壁菌门呈正相关,与拟杆菌门呈负相关。

结论

与口服 LC 给药相比,LC 的皮下给药绕过了其在肝脏中转化为 TMAO 的过程,不会对雄性 ApoE 小鼠动脉粥样硬化的发展产生不利影响。对于需要补充 LC 的患者,LC 的肠外给药可能更为可取。

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