高脂血症动物模型肾功能损伤机制及干预研究进展

doi:10.12300/j.issn.1674-5817.2021.116

摘要/Abstract

摘要：

高脂血症与肾功能损伤密切相关，两者相互影响。脂质沉积于肾脏，通过直接和间接的作用，影响肾小球、肾小管的功能和结构，导致肾功能损伤。而肾功能损伤进一步影响机体脂质代谢，又加剧了高脂血症的进程。目前，除了合成药物以外，还有很多非合成药物在高脂血症动物模型肾功能损伤的干预治疗中取得了很好的疗效。本文概述近年来国内外利用高脂血症动物模型研究肾功能损伤机制及其相关干预治疗的最新进展。

关键词: 高脂血症, 肾功能损伤, 动物模型

Abstract:

Hyperlipidemia is closely related to renal function damage, and they influence each other. Lipid deposition in the kidney affects the function and structure of glomerulus and renal tubules directly and indirectly, resulting in renal function injury. On the contrary, renal function damage further affects lipid metabolism and aggravates the progress of hyperlipidemia. At present, besides synthetic drugs, there are many non-synthetic drugs which have been well verified in the intervention of kidney injury in hyperlipidemia animal model. In this paper, the research progress in the mechanism of renal function damage and the related intervention using hyperlipidemia animal model at home and abroad in recent years were summarized.

Key words: Hyperlipidemia, Kidney injury, Animal model

中图分类号:

Q95-33

周晓丽, 张倩, 钱智勇. 高脂血症动物模型肾功能损伤机制及干预研究进展[J]. 实验动物与比较医学, 2022, 42(3): 213-219.

Xiaoli ZHOU, Qian ZHANG, Zhiyong QIAN. Research Progress on Mechanism and Intervention of Renal Function Injury in Hyperlipidemia Animal Model[J]. Laboratory Animal and Comparative Medicine, 2022, 42(3): 213-219.

参考文献 44

1	赵媛媛, 覃骊兰, 郝二伟. 高血脂症动物模型研究进展[J]. 中国实验方剂学杂志, 2018, 24(18):215-221. DOI:10.13422/j.cnki.syfjx.20181829 .
	ZHAO Y Y, QIN L L, HAO E W. Progress of research on animal model of hyperlipidemia[J]. Chin J Exp Tradit Med Formulae, 2018, 24(18):215-221. DOI:10.13422/j.cnki.syfjx.20181829 .
2	刁婷婷, 闵清. 高脂血症动物模型研究进展[J]. 湖北科技学院学报(医学版), 2018, 32(6):541-545. DOI:10.16751/j.cnki.2095-4646.2018.06.0541 .
	DIAO T T, MIN Q. Research progress of hyperlipidemia animal model[J]. J Hubei Univ Sci Technol Med Sci, 2018, 32(6):541-545. DOI:10.16751/j.cnki.2095-4646.2018.06.0541 .
3	MOORHEAD J F, EL-NAHAS M, CHAN M K, et al. Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease[J]. Lancet, 1982, 320(8311):1309-1311. DOI:10.1016/S0140-6736(82)91513-6 .
4	彭兰, 范能全, 杜晓刚. 高脂血症大鼠肾脏Angptl4变化及辛伐他汀的保护作用[J]. 重庆师范大学学报(自然科学版), 2014, 31(3):88-92. DOI:10.11721/cqnuj20140318 .
	PENG L, FAN N Q, DU X G. The changes of Angptl4in the kidney of hyperlipidemic rats and the protective effect of simvastatin[J]. J Chongqing Norm Univ Nat Sci, 2014, 31(3):88-92. DOI:10.11721/cqnuj20140318 .
5	彭兰. Pdlim2在高脂血症大鼠肾小球足细胞中的表达改变及意义[D]. 重庆: 重庆医科大学, 2014.
	PENG L. Expression and significance of Pdlim2 in the glomerular podocyte of hyperlipidemic rats[D]. Chongqing: Chongqing Medical University, 2014.
6	张维忠, 郭宗琳, 钱泉, 等. 2578例高脂血症者慢性肾脏病分析[J]. 现代临床医学, 2016, 42(1):55-56, 58. DOI:10.11851/j.issn.1673-1557.2016.01.019 .
	ZHANG W Z, GUO Z L, QIAN Q, et al. Analysis of prevalence rate and relating risk factors of chronic kidney disease with hyperlipidemia in 2 578 cases[J]. J Mod Clin Med, 2016, 42(1):55-56, 58. DOI:10.11851/j.issn.1673-1557.2016.01.019 .
7	VAZIRI N D. Lipotoxicity and impaired high density lipoprotein-mediated reverse cholesterol transport in chronic kidney disease[J]. J Ren Nutr, 2010, 20(5): S35-S43. DOI:10.1053/j.jrn.2010.05.010 .[LinkOut]
8	FALKE L L, GHOLIZADEH S, GOLDSCHMEDING R, et al. Diverse origins of the myofibroblast—implications for kidney fibrosis[J]. Nat Rev Nephrol, 2015, 11(4):233-244. DOI:10.1038/nrneph.2014.246 .
9	徐国宾, 朱立华, 夏铁安, 等. 实验性高脂血症对大鼠肾脏的损伤作用[J]. 北京医科大学学报, 1994, 26(5): 370.
	XU G B, ZHU L H, XIA T A, et al. Damage of experimental hyperlipidemia on kidney in rats[J]. J Beijing Med Univ, 1994, 26(5): 370.
10	姚俊成, 牟艳, 窦科. 高血脂对单肾和双肾大鼠肾功能影响分析[J]. 实用医院临床杂志, 2018, 15(1):4-6. DOI:10.3969/j.issn.1672-6170.2018.01.002 .
	YAO J C, MOU Y, DOU K. Effect of hyperglycemia on renal function in rats with single kidney or double kidneys[J]. Pract J Clin Med, 2018, 15(1):4-6. DOI:10.3969/j.issn.1672-6170.2018.01.002 .
11	LIANG H, LILI H, XIN F, et al. Severe hypertriglyceridemia and hypercholesterolemia accelerating renal injury: a novel model of type 1 diabetic hamsters induced by short-term high-fat / high-cholesterol diet and low-dose streptozotocin[J]. BMC Nephrology, 2015, 16(1) .
12	樊爱英, 韩子明, 张贺. 细胞凋亡及Fas和FasL在高脂肾损害中的作用[J]. 陕西医学杂志, 2004, 33(4):303-305, 311. DOI:10.3969/j.issn.1000-7377.2004.04.005 .
	FAN A Y, HAN Z M, ZHANG H. Effect of cell apoptosis and Fas and FasL on rat renal injury in dietary hyperlipidemia[J]. Shaanxi Med J, 2004, 33(4):303-305, 311. DOI:10.3969/j.issn.1000-7377.2004.04.005 .
13	王海燕. 肾脏病学[M]. 3版. 北京: 人民卫生出版社, 2008.
	WANG H. Nephrology (3rd Edition)[M]. Beijing: People Health Publishing House, 2008.
14	RUAN X Z, VARGHESE Z, FERNANDO R, et al. Cytokine regulation of low-density lipoprotein receptor gene transcription in human mesangial cells[J]. Nephrol Dial Transplant, 1998, 13(6):1391-1397. DOI:10.1093/ndt/13.6.1391 .
15	HE L G, WU P F, TAN L, et al. Characteristics of lipid metabolism including serum apolipoprotein M levels in patients with primary nephrotic syndrome[J]. Lipids Health Dis, 2017, 16(1):167. DOI:10.1186/s12944-017-0556-9 .
16	PEI Z W, OKURA T, NAGAO T, et al. Osteopontin deficiency reduces kidney damage from hypercholesterolemia in Apolipoprotein E-deficient mice[J]. Sci Rep, 2016, 6:28882. DOI:10.1038/srep28882 .
17	刘彤, 李龙. 单独应用贝特类降脂药治疗高脂血症肾损害大鼠的机制探讨[J]. 中南药学, 2015, 13(7):716-719. DOI:10.7539/j.issn.1672-2981.2015.07.011 .
	LIU T, LI L. Mechanism of fibrate alone for hyperlipidemia kidney damage in rats[J]. Central South Pharm, 2015, 13(7):716-719. DOI:10.7539/j.issn.1672-2981.2015.07.011 .
18	吴晓静. 高脂喂养大鼠肾脏NF-κB及炎症因子表达变化及利拉鲁肽的干预研究[D]. 承德: 承德医学院, 2017.
	WU X. Expression of NF-nuclear factor kappa B and inflammatory factors in kidney of high fat diet rats and intervention of liraglutide[D]. Chengde: Chengde Medical University, 2017.
19	陈荟婷, 柳洁. 高脂血症对大鼠心肌与肾皮质微细结构的影响[J]. 中国临床研究, 2016, 29(5):577-580. DOI:10.13429/j.cnki.cjcr.2016.05.001 .
	CHEN H T, LIU J. Influence of hyperlipemia on micro-structures of myocardium and renal cortex in rats[J]. Chin J Clin Res, 2016, 29(5):577-580. DOI:10.13429/j.cnki.cjcr.2016.05.001 .
20	ZIAEIAN B, FONAROW G C. Epidemiology and aetiology of heart failure[J]. Nat Rev Cardiol, 2016, 13(6):368-378. DOI:10.1038/nrcardio.2016.25 .
21	MACK M, YANAGITA M. Origin of myofibroblasts and cellular events triggering fibrosis[J]. Kidney Int, 2015, 87(2):297-307. DOI:10.1038/ki.2014.287 .
22	GWINNER W, SCHEUER H, HALLER H, et al. Pivotal role of xanthine oxidase in the initiation of tubulointerstitial renal injury in rats with hyperlipidemia[J]. Kidney Int, 2006, 69(3):481-487. DOI:10.1038/sj.ki.5000121 .
23	SASTRE C, RUBIO-NAVARRO A, BUENDÍA I, et al. Hyperlipidemia-associated renal damage decreases Klotho expression in kidneys from ApoE knockout mice[J]. PLoS One, 2013, 8(12): e83713. DOI:10.1371/journal.pone.0083713 .
24	WEN H X, KUMAR V, LAN X Q, et al. APOL1 risk variants cause podocytes injury through enhancing endoplasmic reticulum stress[J]. Biosci Rep, 2018, 38(4): BSR20171713. DOI:10.1042/BSR20171713 .
25	褚宇东, 李荣山, 田渊, 等. 阿司匹林阻断高脂血症诱导的足细胞内质网应激的机制[J]. 中华肾脏病杂志, 2020, 36(2):139-144. DOI:10.3760/cma.j.issn.1001-7097.2020.02.007 .
	CHU Y D, LI R S, TIAN Y, et al. Aspirin intervenes in hyperlipidemia kidney damage by blocking endoplasmic reticulum stress in podocytes[J]. Chin J Nephrol, 2020, 36(2):139-144. DOI:10.3760/cma.j.issn.1001-7097.2020.02.007 .
26	吴静, 罗朋立. 代谢综合征合并肾损害时血脂变化[J]. 中西医结合心血管病电子杂志, 2020, 8(34):36, 38. DOI:10.16282/j.cnki.cn11-9336/r.2020.34.025 .
	WU J, LUO P L. Changes of blood lipid in metabolic syndrome complicated with renal damage[J]. Cardiovasc Dis Electron J Integr Tradit Chin West Med, 2020, 8(34):36, 38. DOI:10.16282/j.cnki.cn11-9336/r.2020.34.025 .
27	张敏, 高霞. 高脂血症导致慢性肾脏病机制的研究进展[J]. 转化医学杂志, 2020, 9(1):61-65. DOI:10.3969/j.issn.2095-3097.2020.01.017 .
	ZHANG M, GAO X. Advances in research on the mechanism of chronic kidney disease caused by hyperlipidemia[J]. Transl Med J, 2020, 9(1):61-65. DOI:10.3969/j.issn.2095-3097.2020.01.017 .
28	YANG P, XIAO Y Y, LUO X, et al. Inflammatory stress promotes the development of obesity-related chronic kidney disease via CD36 in mice [J]. J Lipid Res, 2017, 58(7):1417-1427. DOI:10.1194/jlr.M076216 .
29	SAJA M F, COOK H T, RUSEVA M M, et al. A triglyceride-rich lipoprotein environment exacerbates renal injury in the accelerated nephrotoxic nephritis model[J]. Clin Exp Immunol, 2018, 192(3):337-347. DOI:10.1111/cei.13111 .[LinkOut]
30	FANG Q L, ZOU C P, ZHONG P, et al. EGFR mediates hyperlipidemia-induced renal injury via regulating inflammation and oxidative stress: the detrimental role and mechanism of EGFR activation[J]. Oncotarget, 2016, 7(17):24361-24373. DOI:10.18632/oncotarget.8222 .
31	孟梅霞, 张锦华, 朱小静, 等. 高脂饮食对大鼠肾组织抑瘤素-M表达的影响[J]. 现代医学, 2017, 45(10):1427-1430. DOI:10.3969/j.issn.1671-7562.2017.10.009 .
	MENG M X, ZHANG J H, ZHU X J, et al. Effects of high-fat diet on the expression of oncostatin-M in rat kidney[J]. Mod Med J, 2017, 45(10):1427-1430. DOI:10.3969/j.issn.1671-7562.2017.10.009 .
32	LIM G B. ANGPTL3: a therapeutic target for atherosclerosis[J]. Nat Rev Cardiol, 2017, 14(7):381. DOI:10.1038/nrcardio. 2017.91 .
33	石晓玲, 曹灵. 他汀类药物对慢性肾功能衰竭中脂代谢异常的研究进展[J]. 广东医学, 2016, 37(19):2987-2990. DOI:10.13820/j.cnki.gdyx.2016.19.038 .
	SHI X L, CAO L. Research progress of statins on abnormal lipid metabolism in chronic renal failure[J]. Guangdong Med J, 2016, 37(19):2987-2990. DOI:10.13820/j.cnki.gdyx.2016.19.038 .
34	CHEN Y, ZHAO L, LI Q, et al. Inflammatory stress reduces the effectiveness of statins in the kidney by disrupting HMGCoA reductase feedback regulation[J]. Nephrol Dial Transplant, 2014, 29(10):1864-1878. DOI:10.1093/ndt/gfu203 .
35	VINICIUS F F, CAMILA P L, GERSON A P, et al. Rapid and direct analysis of statins in human plasma by column-switching liquid chromatography with restricted-access material[J]. Journal of Chromatography B Analytical Technologies in the Biomedical & Life Sciences, 2014, 947-948(1):8-16. DOI:10.1016/j.jchromb.2013.12.002 .
36	LIM C, LIM S, LEE B, et al. Effect of methanol extract of Salviae miltiorrhizae Radix in high-fat diet-induced hyperlipidemic mice[J]. Chin Med, 2017, 12:29. DOI:10.1186/s13020-017-0150-0 .
37	KOUBAA-GHORBEL F, CHAÂBANE M, TURKI M, et al. The protective effects of Salvia officinalis essential oil compared to simvastatin against hyperlipidemia, liver, and kidney injuries in mice submitted to a high-fat diet[J]. J Food Biochem, 2020, 44(4): e13160. DOI:10.1111/jfbc.13160 .
38	宋春蕾, 王玲, 赵永芳, 等. 叶黄素对高脂膳食大鼠尿酸代谢及肾脏功能的影响[J]. 食品工业科技, 2016, 37(17):344-347. DOI:10.13386/j.issn1002-0306.2016.17.059 .
	SONG C L, WANG L, ZHAO Y F, et al. Effects of lutein on serum uric acid and renal function in high-fat-diet induced hyperlipidemia rats[J]. Sci Technol Food Ind, 2016, 37(17):344-347. DOI:10.13386/j.issn1002-0306.2016.17.059 .
39	顾清, 周朋辉, 张静姝, 等. 核黄素对高脂血症大鼠脂质代谢的影响[J]. 中国慢性病预防与控制, 2015, 23(1):34-36. DOI:10.16386/j.cjpccd.issn.1004-6194.2015.01.022 .
	GU Q, ZHOU P H, ZHANG J S, et al. The effects of riboflavin on lipid metabolism in rats with hyperlipidemia[J]. Chin J Prev Control Chronic Dis, 2015, 23(1):34-36. DOI:10.16386/j.cjpccd.issn.1004-6194.2015.01.022 .
40	张大龙, 钱智勇, 张倩, 等. 亚硒酸钠与核黄素联合暴露对高脂饮食大鼠血脂及血清肝生化指标的影响[J]. 环境与健康杂志, 2017, 34(7):579-582. DOI:10.16241/j.cnki.1001-5914.2017.07.005 .
	ZHANG D L, QIAN Z Y, ZHANG Q, et al. Effects of combined supplementation by sodium selenite and riboflavin on blood lipid and liver biochemical indicators in rats with high-fat diet[J]. J Environ Health, 2017, 34(7):579-582. DOI:10.16241/j.cnki.1001-5914.2017.07.005 .
41	周晓丽, 张倩, 张大龙, 等. 富硒酵母对高脂血症大鼠脂代谢的影响[J]. 国际内分泌代谢杂志, 2017, 37(6):361-366, 封3. DOI:10.3760/cma.j.issn.1673-4157.2017.06.001 .
	ZHOU X L, ZHANG Q, ZHANG D L, et al. Effects of selenium enriched yeast on lipid metabolism in rats with hyperlipidemia[J]. Int J Endocrinol Metab, 2017, 37(6):361-366, 封3. DOI:10.3760/cma.j.issn.1673-4157.2017.06.001 .
42	ZHANG Q, QIAN Z Y, ZHOU P H, et al. Effects of oral selenium and magnesium co-supplementation on lipid metabolism, antioxidative status, histopathological lesions, and related gene expression in rats fed a high-fat diet[J]. Lipids Health Dis, 2018, 17(1):165. DOI:10.1186/s12944-018-0815-4 .
43	NIHEI T, MIURA Y, YAGASAKI K. Inhibitory effect of resveratrol on proteinuria, hypoalbuminemia and hyper-lipidemia in nephritic rats[J]. Life Sci, 2001, 68(25):2845-2852. DOI:10.1016/S0024-3205(01)01061-X .
44	许伶, 凌梦玉, 陈超, 等. 白藜芦醇减轻高脂饮食小鼠肾损伤的作用及机制[J]. 安徽医科大学学报, 2019, 54(10):1521-1525. DOI:10.19405/j.cnki.issn1000-1492.2019.10.005 .
	XU L, LING M Y, CHEN C, et al. Effect and mechanism of resveratrol on chronic kidney injury induced by high-lipid diet in mice[J]. Acta Univ Med Anhui, 2019, 54(10):1521-1525. DOI:10.19405/j.cnki.issn1000-1492.2019.10.005 .

[1]	梁天薇, 邓亚胜, 黄慧, 荣娜, 刘鑫, 王玉洁, 林江. 围绝经期综合征动物模型的制备方法及评价指标分析[J]. 实验动物与比较医学, 2024, 44(1): 74-84.
[2]	中国研究型医院学会医学动物实验专家委员会. 自发性脑出血动物模型选择及临床前药物试验指南（2024年版）[J]. 实验动物与比较医学, 2024, 44(1): 3-30.
[3]	刘欣, 石少波, 张翠, 杨波, 曲川. 小鼠自体动静脉内瘘端侧吻合模型的建立与评价[J]. 实验动物与比较医学, 2023, 43(6): 595-603.
[4]	万颖寒, 顾也欣, 袁雨浓, 汤忞, 鲁立. FDA现代化法案2.0给疾病动物模型发展带来的启示和思考[J]. 实验动物与比较医学, 2023, 43(5): 472-481.
[5]	谢淑武, 沈如凌, 林金杏, 范春. 雄性不育药物研发相关实验动物模型建立和应用进展[J]. 实验动物与比较医学, 2023, 43(5): 504-511.
[6]	陈艳娟, 沈如凌. 模式动物疾病模型在结直肠癌医学研究中的应用进展[J]. 实验动物与比较医学, 2023, 43(5): 512-523.
[7]	张睿, 吕美豫, 张建军, 刘金莲, 陈彦, 黄志强, 刘尧, 周澜华. 痤疮动物模型建立及评价研究进展[J]. 实验动物与比较医学, 2023, 43(4): 398-405.
[8]	卢今, 王剑, 朱莲, 严国锋, 马政文, 李垚, 戴建军, 朱寅秋, 周晶. 山羊先兆子痫疾病模型的构建及母体生物学特性评价[J]. 实验动物与比较医学, 2023, 43(4): 371-380.
[9]	俞佳慧, 巩倩, 庄乐南. 肺动脉高压动物模型及其在药物研究中的应用进展[J]. 实验动物与比较医学, 2023, 43(4): 381-397.
[10]	邓亚胜, 林江, 甘池伶, 曾官凤, 黄嘉茵, 邓慧芳, 麻颖贤, 韩丝银. 皮肤光老化动物模型制备要素和受试物数据的文献分析[J]. 实验动物与比较医学, 2023, 43(4): 406-414.
[11]	王雪, 呼永河. 糖尿病小鼠模型的常见种类及其构建要素分析[J]. 实验动物与比较医学, 2023, 43(4): 415-421.
[12]	黄慧, 邓亚胜, 梁天薇, 郑艺清, 范燕萍, 荣娜, 林江. 卵巢储备功能减退动物模型的造模方法评价与分析[J]. 实验动物与比较医学, 2023, 43(4): 422-428.
[13]	相磊, 景金珠, 梁震, 阎国强, 郭文峰, 张萌, 张威, 刘亚军. 基于VOSviewer的肌少症动物模型研究可视化分析[J]. 实验动物与比较医学, 2023, 43(4): 429-439.
[14]	谭志刚, 刘锦信, 郑楚雅, 廖文峰, 冯露平, 彭红丽, 严秀, 卓振建. 神经母细胞瘤动物模型研究进展与应用[J]. 实验动物与比较医学, 2023, 43(3): 288-296.
[15]	赖灿, 李乐乐, 胡塔拉, 孟彦. 肾脏间质纤维化动物模型的研究进展[J]. 实验动物与比较医学, 2023, 43(2): 163-172.