健脾化湿法调控肝脏脂质输出基因甲基化治疗非酒精性脂肪性肝病的理论探讨

刘涛; 徐秋玲

doi:10.3969/j.issn.1001-5256.2019.03.047

健脾化湿法调控肝脏脂质输出基因甲基化治疗非酒精性脂肪性肝病的理论探讨

DOI: 10.3969/j.issn.1001-5256.2019.03.047

刘涛,
徐秋玲

海南医学院

基金项目:

国家自然科学基金资助项目(81760795)；

详细信息

中图分类号: R285
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出版历程
- 出版日期: 2019-03-20

Spleen-strengthening and dampness-removing therapy exerts a therapeutic effect on nonalcoholic fatty liver disease by regulating hepatic MTP promoter methylation

Liu Tao,
Xu QiuLing

Hainan Medical College

Research funding:

摘要

摘要:
非酒精性脂肪性肝病(NAFLD)是糖尿病、心脑血管疾病最常见危险因素,随着生活水平提高,NAFLD患病率急剧上升。微粒体甘油三酯转移蛋白(MTP)是肝脏脂质向外转运的关键酶,MTP启动子甲基化水平增加,是NAFLD肝脏脂质沉积重要因素。中医认为"脾气散精",MTP脂质转运功能可能是"脾气散精"的表现形式之一,临床研究表明,健脾化湿法是治疗NAFLD的重要原则。本文通过综述相关文章,分析健脾化湿法可能通过调控MTP启动子甲基化水平,提高NAFLD肝脏MTP水平,促进肝脏脂质外流,减轻NAFLD脂质沉积,达到改善NAFLD的作用。
- 非酒精性脂肪性肝病 /
- 健脾化湿法 /
- DNA甲基化 /
- 脂蛋白类,LDL /
- 综述
Abstract:
Nonalcoholic fatty liver disease ( NAFLD) is the most common risk factor for diabetes mellitus and cerebrovascular and cardiovascu-lar diseases. The prevalence of NAFLD is increasing rapidly with the improvement in living. Microsome triglyceride transfer protein ( MTP) isa key enzyme for outward transport of liver lipids, and the increase in MTP promoter methylation is an important factor for liver lipid depositionin NAFLD. Traditional Chinese medicine believes that“spleen Qi transfers essence”, and the lipid transport function of MTP may be one of themanifestations of“spleen Qi transfers essence”. Clinical studies have shown that the spleen-strengthening and dampness-removing principleis of great importance in the treatment of NAFLD. By reviewing related articles, this article points out that the spleen-strengthening anddampness-removing therapy can improve NAFLD by regulating MTP promoter methylation, increasing the level of hepatic MTP, promoting theoutflow of liver lipids, and alleviating lipid deposition.
- non-alcoholic fatty liver disease /
- the principle of nourishing spleenand dispelling dampness /
- DNA methylation /
- lipoproteins, LDL /
- review

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参考文献(33)

[1] FRANCQUE SM, van der GRAAFF D, KWANTEN WJ. Non-alcoholic fatty liver disease and cardiovascular risk:Patho-physiological mechanisms and implications[J]. J Hepatol, 2016, 65 (2) :425-443.

[2] RUAN JW, GAO LJ, LIANG XF, et al. Investigation and analy-sis of the incidence of non-alcoholic fatty liver disease inphysical examination population in Haikou area[J]. J ClinHepatol, 2018, 34 (9) :1925-1928. (in Chinese) 阮建文, 高丽娟, 梁雄飞, 等.海口地区体检人群非酒精性脂肪性肝病患病率调查分析[J].临床肝胆病杂志, 2018, 34 (9) :1925-1928.

[3] MUSSO G, CASSADER M, ROSINA F, et al. Impact of currenttreatments on liver disease, glucose metabolism and cardio-vascular risk in non-alcoholic fatty liver disease (NAFLD) :Asystematic review and meta-analysis of randomised trials[J]. Diabetologia, 2012, 55 (4) :885-904.

[4] HSIAO PJ, LEE MY, WANG YT, et al. MTTP-297H polymor-phism reduced serum cholesterol but increased risk of non-alcoholic fatty liver disease-a cross-sectional study[J].BMC Med Genet, 2015, 16:93.

[5] DAI D, WEN F, ZHOU S, et al. Association of MTTP gene va-riants with pediatric NAFLD:A candidate-gene-based anal-ysis of single nucleotide variations in obese children[J]. PLo SOne, 2017, 12 (9) :e0185396.

[6] SHINDO N, FUJISAWA T, SUGIMOTO K, et al. Involvementof microsomal triglyceride transfer protein in nonalcoholicsteatohepatitis in novel spontaneous mouse model[J]. J Hep-atol, 2010, 52 (6) :903-912.

[7] NEWBERRY EP, XIE Y, KENNEDY SM, et al. Prevention ofhepatic fibrosis with liver microsomal triglyceride transfer pro-tein deletion in Liver fatty acid binding protein null mice[J].Hepatology, 2017, 65 (3) :836-852.

[8] HOOPER AJ, BURNETT JR, WATTS GF. Contemporary aspectsof the biology and therapeutic regulation of the microsomal triglyc-eride transfer protein[J]. Circ Res, 2015, 116 (1) :193-205.

[9] LIN M, ZHAO S, SHEN L, et al. Potential approaches to amel-iorate hepatic fat accumulation seen with MTP inhibition[J].Drug Saf, 2014, 37 (4) :213-224.

[10] FUJITA K, IMAJO K, SHINOHARA Y, et al. Novel findings forthe development of drug therapy for various liver diseases:Liver microsomal triglyceride transfer protein activator may bea possible therapeutic agent in non-alcoholic steatohepatitis[J]. J Pharmacol Sci, 2011, 115 (3) :270-273.

[11] WANG X, SUGIMOTO K, FUJISAWA T, et al. Novel effect ofezetimibe to inhibit the development of non-alcoholic fatty liv-er disease in Fatty Liver Shionogi mouse[J]. Hepatol Res, 2014, 44 (1) :102-113.

[12] CHEN YJ, WALLIG MA, JEFFERY EH. Dietary broccoli less-ens development of fatty liver and liver cancer in mice givendiethylnitrosamine and fed a western or control diet[J]. J Nu-tr, 2016, 146 (3) :542-550.

[13] CHANG X, YAN H, FEI J, et al. Berberine reduces methyla-tion of the MTTP promoter and alleviates fatty liver induced bya high-fat diet in rats[J]. J Lipid Res, 2010, 51 (9) :2504-2515.

[14] WANG LJ, ZHANG HW, ZHOU JY, et al. Betaine attenuateshepatic steatosis by reducing methylation of the MTTP promot-er and elevating genomic methylation in mice fed a high-fatdiet[J]. J Nutr Biochem, 2014, 25 (3) :329-336.

[15] KANG KA, KIM HS, KIM DH, et al. The role of a ginseng sap-onin metabolite as a DNA methyltransferase inhibitor in color-ectal cancer cells[J]. Int J Oncol, 2013, 43 (1) :228-236.

[16] JIA XY, YANG WZ, SHEN ZW, et al. Clinical study on preven-tion and treatment of thrombocytopenia induced by demethyla-tion of myelodysplastic syndrome with Bushen Jianpi ZhixuePrescription[J]. Shanghai J Tradit Chin Med, 2015, 49 (12) :47-49. (in Chinese) 贾新颜, 杨文忠, 沈桢巍, 等.补肾健脾止血方防治骨髓增生异常综合征去甲基化治疗致血小板减少临床研究[J].上海中医药杂志, 2015, 49 (12) :47-49.

[17] LI N, GONG LH, CHENG XP. Effect of Chinese herbal medi-cine on methylation of estrogen receptor gene and matrix met-alloproteinase-9 gene in patients with acute coronary syn-drome[J]. J Emerg Tradit Chin Med, 2015, 24 (10) :1746-1749. (in Chinese) 李楠, 宫丽鸿, 程修平.复方中药对急性冠脉综合征患者雌激素受体基因与基质金属蛋白酶-9基因甲基化水平的影响[J].中国中医急症, 2015, 24 (10) :1746-1749.

[18] LI ZG, ZHANG W, XIA KH, et al. Effect of Jiedu Huayu JianpiPrescription on methylation of Thbs 1 gene in gastric mucosalhyperplasia[J]. World Chin J Dig, 2015, 23 (2) :243-248. (in Chinese) 李志钢, 张伟, 夏宽宏, 等.解毒化瘀健脾方对胃黏膜异型增生Thbs1基因甲基化的作用[J].世界华人消化杂志, 2015, 23 (2) :243-248.

[19] ZHANG LH. Clinical observation of regulating liver and spleenmethod in the treatment of non-alcoholic fatty liver disease[J]. China Med Herald, 2015, 14 (13) :84-87. (in Chinese) 张立宏.调肝理脾法治疗非酒精性脂肪肝临床观察[J].中国医药导报, 2015, 14 (13) :84-87.

[20] ZHANG LD, WEI W, SUN XH, et al. Cross-sectional surveyof TCM disease-body-syndrome of nonalcoholic fatty liver[J]. World Chin J Dig, 2015, 23 (33) :5296-5302. (in Chi-nese) 张良登, 魏玮, 孙晓红, 等.非酒精性脂肪肝中医病-体-证横断面调查[J].世界华人消化杂志, 2015, 23 (33) :5296-5302.

[21] XU L, MI YQ, LI P. Objective study on TCM syndromes ofnonalcoholic fatty liver[J]. China J Tradit Chin Med Pharma, 2015, 30 (7) :2544-2547. (in Chinese) 徐亮, 宓余强, 李萍.非酒精性脂肪肝中医证型客观化研究[J].中华中医药杂志, 2015, 30 (7) :2544-2547.

[22] CHEN Y, LENG X, DU Y, et al. Distribution characteristics ofTCM syndromes of non-alcoholic fatty liver and correlation a-nalysis with clinical indicators[J]. Chin Arch Tradit Chin Med, 2014, 32 (7) :1556-1558. (in Chinese) 陈阳, 冷雪, 杜莹, 等.非酒精性脂肪肝中医证候分布特点及与临床指标的相关性分析[J].中华中医药学刊, 2014, 32 (7) :1556-1558.

[23] XIONG Y, ZHANG SS, ZHOU T, et al. Effect of Tiaogan LipiPrescription on adiponectin, resistin and tumor necrosis factor-alpha in patients with non-alcoholic fatty liver[J]. China JTradit Chin Med Pharma, 2015, 30 (12) :4419-4422. (in Chi-nese) 熊鹰, 张声生, 周滔, 等.调肝理脾方对非酒精性脂肪肝患者脂联素、抵抗素及肿瘤坏死因子α的影响[J].中华中医药杂志, 2015, 30 (12) :4419-4422.

[24] SHENG QS, NONG H, WU FS, et al. Observation on the ther-apeutic effect of Zhishi Xiaopi Pill on non-alcoholic fatty liverof spleen deficiency and qi stagnation type[J]. Liaoning JTradit Chin Med, 2013, 40 (5) :932-934. (in Chinese) 盛庆寿, 农慧, 吴发胜, 等.枳实消痞丸治疗脾虚气滞型非酒精性脂肪肝疗效观察[J].辽宁中医杂志, 2013, 40 (5) :932-934.

[25] LIU Y, ZHU LY, WANG YR, et al. Clinical study of Heze Jian-gzhi Oral Liquid in the treatment of non-alcoholic fatty liver ofliver depression and spleen deficiency type[J]. Chin TraditPatent Med, 2014, 36 (8) :1607-1612. (in Chinese) 刘晏, 朱凌云, 王跃荣, 等.荷泽降脂口服液治疗肝郁脾虚型非酒精性脂肪肝的临床研究[J].中成药, 2014, 36 (8) :1607-1612.

[26] WANG JY, ZHANG YZ, ZOU JQ, et al. Meta-analysis of ran-domized controlled trial of Shenling Baizhu Powder in the treat-ment of non-alcoholic fatty liver[J]. J Liaoning Univ TraditChin Med, 2017, 19 (9) :110-114. (in Chinese) 王珏云, 张异卓, 邹金桥, 等.参苓白术散治疗非酒精性脂肪肝随机对照试验Meta分析[J].辽宁中医药大学学报, 2017, 19 (9) :110-114.

[27] ZHANG YP, YANG QH, JIN L, et al. Effects of ShenlingBaizhu Powder on liver lipid metabolism and SIRT1/UCP2pathway in NAFLD rats[J]. Tradit Chin Drug Res Clin Phar-macol, 2016, 27 (1) :38-44. (in Chinese) 张玉佩, 杨钦河, 金玲, 等.参苓白术散对NAFLD大鼠肝脏脂质代谢及SIRT1/UCP2通路的影响[J].中药新药与临床药理, 2016, 27 (1) :38-44.

[28] JIN L, YANG QH, ZHANG YP, et al. Effects of Shenling BaizhuPowder on Nrf2/ARE signaling pathway in liver tissue of NAFLD rats[J]. Tradit Chin Drug Res Clin Pharmacol, 2016, 27 (3) :327-332. (in Chinese) 金玲, 杨钦河, 张玉佩, 等.参苓白术散对NAFLD大鼠肝组织Nrf2/ARE信号通路的影响[J].中药新药与临床药理, 2016, 27 (3) :327-332.

[29] SHIN SS, YOON M. Korean red ginseng (Panax ginseng) in-hibits obesity and improves lipid metabolism in high fat diet-fed castrated mice[J]. J Ethnopharmacol, 2018, 210:80-87.

[30] LEE JB, YOON SJ, LEE SH, et al. Ginsenoside Rg3 ameliora-ted HFD-induced hepatic steatosis through downregulation ofSTAT5-PPARγ[J]. J Endocrinol, 2017, 235 (3) :223-235.

[31] MIAO H, ZHAO YH, VAZIRI ND, et al. Lipidomics biomarkersof diet-induced hyperlipidemia and its treatment with poriacocos[J]. J Agric Food Chem, 2016, 64 (4) :969-979.

[32] MENG SX, LIU Q, TANG YJ, et al. A recipe composed of chi-nese herbal active components regulates hepatic lipid metabo-lism of NAFLD in vivo and in vitro[J]. Biomed Res Int, 2016, 2016:1026852.

[33] YU F, GAO J, ZENG Y, et al. Inhibition of Coix seed extracton fatty acid synthase, a novel target for anticancer activity[J]. J Ethnopharmacol, 2008, 119 (2) :252-258.

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