腹腔注射富氢生理盐水促进高脂血症金黄地鼠胆固醇逆向转运和血脂水平降低

首页 > 按月查看>2024年第12月 >1041-1050

腹腔注射富氢生理盐水促进高脂血症金黄地鼠胆固醇逆向转运和血脂水平降低
DOI:
                        
                    
作者:
                        陈微1,2,3陈微
山东第一医科大学第二附属医院,山东省泰安市 271000;山东第一医科大学临床与基础医学院,山东省泰安市 271000;山东第一医科大学泰山氢生物医学研究院,山东省泰安市 271000
在知网中查找
在百度中查找
在本站中查找
王新程2,3王新程
山东第一医科大学临床与基础医学院,山东省泰安市 271000;山东第一医科大学泰山氢生物医学研究院,山东省泰安市 271000
在知网中查找
在百度中查找
在本站中查找
陈远2,3陈远
山东第一医科大学临床与基础医学院,山东省泰安市 271000;山东第一医科大学泰山氢生物医学研究院,山东省泰安市 271000
在知网中查找
在百度中查找
在本站中查找
秦树存1,2,3秦树存
山东第一医科大学第二附属医院,山东省泰安市 271000;山东第一医科大学临床与基础医学院,山东省泰安市 271000;山东第一医科大学泰山氢生物医学研究院,山东省泰安市 271000
在知网中查找
在百度中查找
在本站中查找

                    
作者单位:(1.山东第一医科大学第二附属医院,山东省泰安市 271000;2.山东第一医科大学临床与基础医学院,山东省泰安市 271000;3.山东第一医科大学泰山氢生物医学研究院,山东省泰安市 271000)
作者简介:陈微,博士,讲师,主要研究方向为氢分子在脂代谢性疾病中的作用及机制,E-mail:13181815068@163.com。通信作者秦树存,教授,主要研究方向为胆固醇代谢与心脑血管疾病的基础和临床研究,E-mail:scqin@sdfmu.edu.cn。
通讯作者:
基金项目:国家自然科学基金项目(NSFC 81929002)；山东第一医科大学学术提升计划项目(2019QL010)；山东省高校重大疾病与氢医学转化应用重点实验室(鲁教科字[2022]7号)；山东省医药卫生氢分子生物医学研究重点实验室(鲁卫科教字[2022]3号)

Intraperitoneal injection of hydrogen-rich saline promotes reverse cholesterol transport and decreases plasma lipid levels in golden hamster with hyperlipidemia

Author:

CHEN Wei ^{^1,2,3}
CHEN Wei
The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong 271000, China;School of Clinical and Basic Medicine, Shandong First Medical University, Taian, Shandong 271000, China;Taishan Institute of Hydrogen Biomedical Research, Shandong First Medical University, Taian, Shandong 271000, China
在知网中查找
在百度中查找
在本站中查找
WANG Xincheng ^{^2,3}
WANG Xincheng
School of Clinical and Basic Medicine, Shandong First Medical University, Taian, Shandong 271000, China;Taishan Institute of Hydrogen Biomedical Research, Shandong First Medical University, Taian, Shandong 271000, China
在知网中查找
在百度中查找
在本站中查找
CHEN Yuan ^{^2,3}
CHEN Yuan
School of Clinical and Basic Medicine, Shandong First Medical University, Taian, Shandong 271000, China;Taishan Institute of Hydrogen Biomedical Research, Shandong First Medical University, Taian, Shandong 271000, China
在知网中查找
在百度中查找
在本站中查找
QIN Shucun ^{^1,2,3}
QIN Shucun
The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong 271000, China;School of Clinical and Basic Medicine, Shandong First Medical University, Taian, Shandong 271000, China;Taishan Institute of Hydrogen Biomedical Research, Shandong First Medical University, Taian, Shandong 271000, China
在知网中查找
在百度中查找
在本站中查找

Affiliation:

1.The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong 271000, China;2.School of Clinical and Basic Medicine, Shandong First Medical University, Tai'an, Shandong 271000, China;3.Taishan Institute of Hydrogen Biomedical Research, Shandong First Medical University, Tai'an, Shandong 271000, China)

Fund Project:

摘要

图/表

访问统计

参考文献

相似文献

引证文献

资源附件

摘要:

目的]观察腹腔注射富氢生理盐水(HRS)对高脂饲料饲喂金黄地鼠胆固醇逆向转运的影响。 [方法]将雄性金黄地鼠分为三组:正常饮食组、高脂饮食组和高脂饮食＋HRS组。高脂饲料饲喂和HRS同时持续干预12周后,将³H-胆固醇标记的巨噬细胞注射到金黄地鼠体内,检测血液、肝脏、胆汁和粪便中的放射性；通过RT-qPCR和Western blot检测肝脏组织中胆固醇逆向转运相关基因转录水平和蛋白表达水平。 [结果]长期的高脂饲料饲喂诱导金黄地鼠出现明显的高脂血症和肝脏脂质蓄积。与高脂饮食组相比,高脂饮食+HRS组金黄地鼠体质量下降(P＜0.01),血浆总胆固醇(TC)、低密度脂蛋白胆固醇(LDLC)显著降低(P＜0.05),甘油三酯(TG)略有降低(P＝0.11),高密度脂蛋白胆固醇(HDLC)显著升高(P＜0.01),血浆和肝脏中氧化应激指标丙二醛(MDA)显著降低(P＜0.05或P＜0.01),抗氧化指标谷胱甘肽(GSH)显著升高(P＜0.01),肝体比略下降(P＝0.05),肝脏中TC和TG分别下降10.8%(P＝0.05)和20.1%(P＜0.01),肝脏脂肪变性明显缓解,但是炎症因子水平没有明显变化。同位素示踪结果显示,与高脂饮食组相比,HRS组金黄地鼠血浆³H放射性在24 h和48 h分别下降16.5%(P＜0.01)和8.9%(P＜0.05),肝脏、胆汁和粪便中的³H放射性分别升高了1.2倍(P＜0.05)、1.2倍(P＝0.08)和1.1倍(P＝0.08)。RT-qPCR和Western blot结果显示,HRS干预使高脂饲料饲喂金黄地鼠肝脏CD36、清道夫受体B1(SR-B1)和低密度脂蛋白受体(LDLR)蛋白水平分别降低39.5%(P＜0.05)、40.5%(P＜0.01)和28.0%(P＜0.01),ATP结合盒转运体G5(ABCG5)和固醇调节元件结合蛋白2(SREBP2)蛋白水平分别升高1.5倍(P＜0.05)和1.3倍(P＜0.01),同时ATP结合盒转运体A1和G8的mRNA水平分别升高2.9倍(P＜0.05)和3.2倍(P＜0.01)。 [结论]腹腔注射HRS可促进高脂饲料饲喂金黄地鼠胆固醇逆向转运,并发挥降血脂效应；此外,腹腔注射HRS也可能通过抑制肝脏对脂质的摄取和促进肝脏胆固醇外排来缓解肝脏脂质蓄积。

关键词:富氢生理盐水;高脂血症;金黄地鼠;胆固醇逆向转运;血脂

Abstract:

Aim To observe the effect of intraperitoneal injection of hydrogen-rich saline (HRS) on reverse cholesterol transport in golden hamsters with high fat diet. Methods The male golden hamsters were divided into three groups:chow diet group, high-fat diet group, and high-fat diet＋HRS group. After 12 weeks of high-fat diet feeding and HRS administration, macrophages labeled with ³H-cholesterol were injected into hypercholesterolemic golden hamsters, and then radioactivity in blood, liver, bile, and feces was measured. RT-qPCR and Western blot were used to assess the transcription and protein expression levels of cholesterol reverse transport-related genes in liver tissue. Results Long-term feeding with a high-fat diet induced significant hyperlipidemia and liver lipid accumulation in golden hamsters. Compared with the high-fat diet group, after HRS intervention, the body mass of golden hamsters decreased (P＜0.01), plasma TC and LDLC significantly decreased (P＜0.05), TG slightly decreased (P＝0.11), HDLC significantly increased (P＜0.01), oxidative stress index MDA in plasma and liver significantly decreased (P＜0.05 or P＜0.01), antioxidant index glutathione (GSH) significantly increased (P＜0.01), liver weight/body weight ratio slightly decreased (P＝0.05), TC and TG in liver decreased by 10.8% (P＝0.05) and 20.1% (P＜0.01), respectively. Liver steatosis was significantly relieved, but there was no significant change in inflammatory factor levels. In isotopic tracing, high-fat diet fed golden hamsters treated with HRS showed decreased ³H radioactivity in plasma at 24 and 48 hours by 16.5% (P＜0.01) and 8.9% (P＜0.05) respectively, while increased ³H radioactivity was observed in liver, bile, and feces by 1.2-fold (P＜0.05), 1.2-fold (P＝0.08), and 1.1-fold (P＝0.08) respectively, compared to those fed a high-fat diet alone. Furthermore, RT-qPCR and Western blot analyses of liver tissue demonstrated that HRS intervention resulted in a decrease of CD36, scavenger receptor-B1 (SR-B1), and low density lipoprotein receptor (LDLR) protein levels by 39.5% (P＜0.05), 40.5% (P＜0.01), and 28.0% (P＜0.01) respectively, an increase of ATP-binding cassette transporter G5 (ABCG5) and sterol regulatory element-binding protein (SREBP2) protein levels by 1.5-fold (P＜0.05) and 1.3-fold (P＜0.01), and an increase of mRNA levels of ATP-binding cassette transporter A1 and G8 by 2.9-fold (P＜0.05) and 3.2-fold (P＜0.01) respectively in high-fat diet-fed hamsters. Conclusions Intraperitoneal injection of HRS promotes reverse cholesterol transport in high-fat diet-fed golden hamsters and exerts lipid-lowering effects. Additionally, intraperitoneal injection of HRS may alleviate hepatic lipid accumulation by inhibiting hepatic lipid uptake and promoting cholesterol excretion from liver.

Key words:hydrogen-rich saline; gold hamster; hyperlipidemia; reverse cholesterol transport; plasma lipids

参考文献

[1] 中国血脂管理指南修订联合专家委员会.中国血脂管理指南(2023年).中国循环杂志, 3,8(3):237-271.Joint Expert Committee on Revision of Chinese Blood Lipid Management Guidelines.Chinese guidelines for lipid management (2023).Chin Circ J, 3,8(3):237-271.

[2] LUO J, YANG H, SONG B L.Mechanisms and regulation of cholesterol homeostasis.Nat Rev Mol Cell Biol, 0,1(4):225-245.

[3] QIN S.Role of hydrogen in atherosclerotic disease:from bench to bedside.Curr Pharm Des, 1,7(5):713-722.

[4] 谢云博, 陈军, 刘伯言, 等.氢分子在心血管病及其风险因素防控中的作用和分子机制.中国病理生理杂志, 1,7(12):2264-2270.XIE Y B, CHEN J, LIU B Y, et al.Role and molecular mechanism of hydrogen molecule in prevention and control of cardiovascular diseases and its risk factors.Chin J Pathophysiol, 1,7(12):2264-2270.

[5] SONG G, LIN Q, ZHAO H, et al.Hydrogen activates ATP-binding cassette transporter a1-dependent efflux ex vivo and improves high-density lipoprotein function in patients with hypercholesterolemia:a double-blinded, randomized, and placebo-controlled trial.J Clin Endocrinol Metab, 5,0(7):2724-2733.

[6] QIU X, YE Q, SUN M, et al.Saturated hydrogen improves lipid metabolism disorders and dysbacteriosis induced by a high-fat diet.Exp Biol Med (Maywood), 0,5(6):512-521.

[7] ZONG C, SONG G, YAO S, et al.Cigarette smoke exposure impairs reverse cholesterol transport which can be minimized by treatment of hydrogen-saturated saline.Lipids Health Dis, 5,4:159.

[8] 刘伯言, 贾修滨, 薛俊莉, 等.顶空-气相色谱法与氢气微电极法用于富氢水中氢气含量的检测.食品工业科技, 3,4(2):352-357.LIU B Y, JIA X B, XUE J L, et al.Determination of hydrogen concentration in hydrogen-rich water by headspace gas chromatography and hydrogen microelectrode.Sci Technol Food Ind, 3,4(2):352-357.

[9] RIOS F J, TOUYZ R M, MONTEZANO A C.Isolation and differentiation of murine macrophages.Methods Mol Biol, 7,7:297-309.

[10] TRGUIER M, BRIAND F, BOUBACAR A, et al.Diet-induced dyslipidemia impairs reverse cholesterol transport in hamsters.Eur J Clin Invest, 1,1(9):921-928.

[11] SI Y, ZHANG Y, CHEN X, et al.Phospholipid transfer protein deficiency in mice impairs macrophage reverse cholesterol transport in vivo.Exp Biol Med (Maywood), 6,1(13):1466-1472.

[12] 温元元, 薛俊莉, 刘伯言, 等.氢分子增强高密度脂蛋白介导的胆固醇排出功能:从动物实验到临床试验.中国动脉硬化杂志, 2,0(11):996-1000.WEN Y Y, XUE J L, LIU B Y, et al.Hydrogen molecule enhances high density lipoprotein-mediated cholesterol efflux:from animal experiments to clinical trials.Chin J Arterioscler, 2,0(11):996-1000.

[13] LIU B, LV P, ZHANG X, et al.Zn-Fe primary battery-enabled controlled hydrogen release in stomach for improving insulin resistance in obesity-associated type 2 diabetes.Bioact Mater, 4,3:242-250.

[14] LEBARON T W, SINGH R B, FATIMA G, et al.The effects of 24-week, high-concentration hydrogen-rich water on body composition, blood lipid profiles and inflammation biomarkers in men and women with metabolic syndrome:a randomized controlled trial.Diabetes Metab Syndr Obes, 0,3:889-896.

[15] SONG G, LI M, SANG H, et al.Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome.J Lipid Res, 3,4(7):1884-1893.

[16] MORVARIDZADEH M, ZOUBDANE N, HESHMATI J, et al.High-density lipoprotein metabolism and function in cardiovascular diseases:what about aging and diet effects?.Nutrients, 4,6(5):653.

[17] ZONG C, SONG G, YAO S, et al.Administration of hydrogen-saturated saline decreases plasma low-density lipoprotein cholesterol levels and improves high-density lipoprotein function in high-fat diet-fed hamsters.Metabolism, 2,1(6):794-800.

[18] LIU B, ZHAO M, XUE J, et al.Hydrogen influences HDL-associated enzymes and reduces oxidized phospholipids levels in rats fed with a high-fat diet.Life Sci, 1,7:118945.

[19] BEN-AICHA S, BADIMON L, VILAHUR G.Advances in HDL:much more than lipid transporters.Int J Mol Sci, 0,1(3):732.

[20] SONG G, TIAN H, QIN S, et al.Hydrogen decreases athero-susceptibility in apolipoprotein B-containing lipoproteins and aorta of apolipoprotein E knockout mice.Atherosclerosis, 2,1(1):55-65.

[21] TAO G, LIU F, JIN Z, et al.A strategy of local hydrogen capture and catalytic hydrogenation for enhanced therapy of chronic liver diseases.Theranostics, 3,3(8):2455-2470.

[22] TAO G, ZHANG G, CHEN W, et al.A randomized, placebo-controlled clinical trial of hydrogen/oxygen inhalation for non-alcoholic fatty liver disease.J Cell Mol Med, 2,6(14):4113-4123.

[23] IIO A, ITO M, ITOH T, et al.Molecular hydrogen attenuates fatty acid uptake and lipid accumulation through downregulating CD36 expression in HepG2 cells.Med Gas Res, 3,3(1):6.

[24] XU L, GUO W, DAI J, et al.Hydrogen gas alleviates acute ethanol-induced hepatotoxicity in mice via modulating TLR4/9 innate immune signaling and pyroptosis.Int Immunopharmacol, 4,7:111399.

[25] ADZAVON Y M, XIE F, YI Y, et al.Long-term and daily use of molecular hydrogen induces reprogramming of liver metabolism in rats by modulating NADP/NADPH redox pathways.Sci Rep, 2,2(1):3904.

[26] TAKAHASHI S, NAKAGAWA K, NAGATA W, et al.A preliminary therapeutic study of the effects of molecular hydrogen on intestinal dysbiosis and small intestinal injury in high-fat diet-loaded senescence-accelerated mice.Nutrition, 4,2:112372.

引用本文

陈微,王新程,陈远,秦树存.腹腔注射富氢生理盐水促进高脂血症金黄地鼠胆固醇逆向转运和血脂水平降低[J].中国动脉硬化杂志,2024,32(12):1041~1050.

复制

文章指标

点击次数:47
下载次数: 1764

历史

收稿日期:2023-12-24
最后修改日期:2024-05-29
录用日期:
在线发布日期: 2025-01-06

政策指南

引用本文

分享

文章指标

历史