从脂肪组织血管生成探讨益气活血方药治疗肥胖症
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摘要
脂肪组织血管系统与脂肪细胞功能活性关系密切,其不仅为脂肪细胞提供氧气及营养物质,而且在调节脂肪细胞代谢中也发挥重要作用。在机体生命周期内,因代谢需求的变化,脂肪组织类别、形态、功能亦随之发生改变,而血管生成直接参与了调控脂肪细胞可塑性。因而明确血管生成在脂肪组织中的作用,可能为肥胖症及相关代谢性疾病的治疗提供新思路。益气活血方药可用于治疗肥胖症,可能具有调节脂肪组织血管系统作用。本文回顾近年研究,阐述血管生成与脂肪组织功能关系,并探讨益气活血方药对脂肪组织血管生成的作用。
Recent studies showed that adipose vasculature system, which not only supplied oxygen and nutrients for adipocytes and also played an important role in adipocytes metabolism, was closely associated with adipocyte activity. During the entire adulthood, the type, form and function of adipose tissue change with the metabolic status of the host, and angiogenesis is directly involved in regulating adipocyte plasticity. Therefore, to clarify the effect of angiogenesis in adipose tissue may provide a new therapeutic strategy for obesity and related metabolic diseases. Benefiting qi and activating blood(BQAB) was used for clinical treatment of obesity, suggesting the possibility of regulating vasculature function in adipose tissue. This paper reviews the recent studies, elaborates the relationship between angiogenesis and adipose tissue function, and explore the effect of BQAB on adipose tissue angiogenesis.
Recent studies showed that adipose vasculature system, which not only supplied oxygen and nutrients for adipocytes and also played an important role in adipocytes metabolism, was closely associated with adipocyte activity. During the entire adulthood, the type, form and function of adipose tissue change with the metabolic status of the host, and angiogenesis is directly involved in regulating adipocyte plasticity. Therefore, to clarify the effect of angiogenesis in adipose tissue may provide a new therapeutic strategy for obesity and related metabolic diseases. Benefiting qi and activating blood(BQAB) was used for clinical treatment of obesity, suggesting the possibility of regulating vasculature function in adipose tissue. This paper reviews the recent studies, elaborates the relationship between angiogenesis and adipose tissue function, and explore the effect of BQAB on adipose tissue angiogenesis.
引文
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[22] Arany Z,Foo SY,Ma Y,et al.HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha [J].Nature,208,451(7181):1008-1012.
[23] Jo DH,Park SW,Cho CS,et al.Intravitreally injected Anti-VEGF antibody reduces brown fat in neonatal mice [J].PLoS One,2015,10(7):e0134308.
[24] Lim S,Honek J,Xue Y,et al.Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice[J].Nat Protoc,2012,7(3):606-615.
[25] Wang B,Fu X,Liang X,et al.Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFRα+ adipose progenitors[J].Cell Discov,2017,3:17036.
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[29] 周小青,梁昊,孙翔,等.冠心病中医血瘀证型与冠状动脉造影结果相关性的 Meta分析[J].中国循证医学杂志,2012,12(12):1470-1477.
[30] 黄凤,段行武,董建勋,等.不同浓度益气活血方含药血清对大鼠骨髓间充质干细胞体外增殖及VEGF表达的影响 [J].中医杂志,2014,55(13):1132-1135.
[31] 虢灿杰,唐涛,罗杰坤,等.益气活血法对脑出血大鼠脑组织促血管生成素-1及其受体表达的影响 [J].中国中西医结合急救杂志,2007,14(3):138-141.
[2] Cypess AM,Lehman S,Williams G,et al.Identification and importance of brown adipose tissue in adult humans [J].N Engl J Med,2009,360(15):1509-1517.
[3] Cao Y.Adipose tissue angiogenesis as therapeutic target for obesity and metabolic diseases [J].Nat Rev Drug Discov,2010,9(2):107-115.
[4] Br?kenhielm E,Cao R,Gao B,et al.Angiogenesis inhibitor,TNP-470,prevents diet-induced and genetic obesity in mice [J].Circ Res,2004,94(12):1579-1588.
[5] 杨仕权,陈贵海,邓巍,等.血府逐瘀合二陈汤对肥胖大鼠内脏脂肪素等脂肪因子含量的影响[J].北京中医药大学学报,2015,38(2):104-110.
[6] 孙璐,唐咸玉,张鹏,等.益气化痰活血法改善超重/肥胖2型糖尿病患者糖脂代谢紊乱及肥胖抑制素的临床观察[J].中国实验方剂学杂志,2017,23(6):180-185.
[7] 李吉武,唐爱华,赵伟,等.温阳益气活血方对肥胖2型糖尿病患者肠道菌群变化及脂质代谢的影响[J].中医杂志,2015,56(5):409-413.
[8] 王培利,雷燕,王承龙.益气活血中药对血管生成PI3K和MAPK信号途径的影响 [J].中西医结合心脑血管病杂志,2010,8(9):1083-1085.
[9] 苑维,金明,潘琳,等.益气活血方对糖尿病大鼠视网膜微血管病变血管内皮生长因子表达的影响[J].中华中医药杂志,2010,25(5):758-760.
[10] van Marken Lichtenbelt WD,Vanhommerig JW,Smulders NM,et al.Cold-activated brown adipose tissue in healthy men [J].N Engl J Med,2009,360(15):1500-1508.
[11] Wu J,Bostr?m P,Sparks LM,et al.Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human [J].Cell,2012,150(2):366-376.
[12] Corvera S,Gealekman O.Adipose tissue angiogenesis:impact on obesity and type-2 diabetes [J].Biochim Biophys Acta,2014,1842(3):463-472.
[13] Ferrara N,Kerbel RS.Angiogenesis as a therapeutic target [J].Nature,2005,438(7070):967-974.
[14] Xue Y,Petrovic N,Cao R,et al.Hypo-xia-independent angiogenesis in adipose tissues during cold acclimation [J].Cell Metab,2009,9(1):99-109.
[15] Ye J.Emerging role of adipose tissue hypoxia in obesity and insulin resistance [J].Int J Obes (Lond),2009,33(1):54-66.
[16] Ye J,Gao Z,Yin J,et al.Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice [J].Am J Physiol Endocrinol Metab,2007,293(4):E1118-E1128.
[17] Kim KL,Suh W.Apatinib,an inhibitor of vascular endothelial growth factor receptor 2,suppresses pathologic ocular neovascularization in mice [J].Invest Ophthalmol Vis Sci,2017,58(9):3592-3599.
[18] Xue Y,Cao R,Nilsson D,et al.FOXC2 controls Ang-2 expression and modulates angiogenesis,vascular patterning,remodeling,and functions in adipose tissue [J].Proc Natl Acad Sci U S A,2008,105(29):10167-10172.
[19] Cao Y.Angiogenesis and vascular functions in modulation of obesity,adipose metabolism,and insulin sensitivity [J].Cell Metab,2013,18(4):478-489.
[20] Sung HK,Doh KO,Son JE,et al.Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis [J].Cell Metab,2013,17(1):61-72.
[21] Pino E,Wang H,McDonald ME,et al.Roles for peroxisome proliferator-activated receptor γ (PPARγ) and PPARγ co-activators 1α and 1β in regulating resp-onse of white and brown adipocytes to hypoxia [J].J Biol Chem,2012,287(22):18351-18358.
[22] Arany Z,Foo SY,Ma Y,et al.HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha [J].Nature,208,451(7181):1008-1012.
[23] Jo DH,Park SW,Cho CS,et al.Intravitreally injected Anti-VEGF antibody reduces brown fat in neonatal mice [J].PLoS One,2015,10(7):e0134308.
[24] Lim S,Honek J,Xue Y,et al.Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice[J].Nat Protoc,2012,7(3):606-615.
[25] Wang B,Fu X,Liang X,et al.Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFRα+ adipose progenitors[J].Cell Discov,2017,3:17036.
[26] 高世试.医学真传[M].南京:江苏科学技术出版社,1981:21.
[27] 杨士瀛.仁斋直指方[M].上海:第二军医大学出版社,2006:389.
[28] 陈士铎.石室秘录[M].北京:人民卫生出版社,2006:9.
[29] 周小青,梁昊,孙翔,等.冠心病中医血瘀证型与冠状动脉造影结果相关性的 Meta分析[J].中国循证医学杂志,2012,12(12):1470-1477.
[30] 黄凤,段行武,董建勋,等.不同浓度益气活血方含药血清对大鼠骨髓间充质干细胞体外增殖及VEGF表达的影响 [J].中医杂志,2014,55(13):1132-1135.
[31] 虢灿杰,唐涛,罗杰坤,等.益气活血法对脑出血大鼠脑组织促血管生成素-1及其受体表达的影响 [J].中国中西医结合急救杂志,2007,14(3):138-141.
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