针刺治疗胰岛素抵抗机制的研究进展与思考
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摘要
胰岛素抵抗是多种代谢性疾病的共同病理基础。笔者基于近10年国内外胰岛素抵抗发病机制及针刺治疗胰岛素抵抗机制的相关研究,从以下几方面进行了分析总结:(1)针刺对中枢神经元的影响;(2)针刺对外周靶器官的影响;(3)针刺对机体炎性反应及氧化应激的影响;(4)针刺对胰岛β细胞的影响。笔者认为今后的研究应重视腧穴特异性、配伍方法及刺激参数对针刺治疗胰岛素抵抗的影响,这对揭示针刺的临床应用规律,优化临床治疗方案具有重要的意义。
Insulin resistance(IR)is a common pathophysiological basis of many chronic diseases,such as obesity,type2 diabetes mellitus(T2 DM),nonalcoholic fatty liver disease,cerebral vascular disease,cardiovascular and neurodegenerative diseases,etc.Acupuncture therapy has been demonstrated to have a positive role in reducing IR level in clinical practice.In the present paper,we summarized development of researches on the mechanism of acupuncture therapy underlying improvement of IR in recent 10 years from 1)regulating expression of hypothalamic phosphatidylinositol-3-kinase(PI3 K)-p85 and PI3 K-P110 proteins in obesity rats;2)regulating the levels of some related proteins of insulin target tissues(liver and skeletal muscle),such as insulin receptor substrate-1(IRS)-1 and-2,glucose transporter mRNAs and proteins,sterol regulatory element-binding protein 1(SREBP-1)and fatty acid synthetase proteins;3)suppressing inflammatory reaction of liver tissue and down-regulating serum adiponectin in T2 DM rats;4)raising the activity of superoxide dismutase(SOD)and reducing the levels of reactive oxygen species,and malondialdehyde(MDA)contents of quadriceps femoris in spontaneous IR rats;and 5)attenuating structural injury of pancreas islet and apoptosis of pancreaticβcells in diabetes rats.Multi-levels and various systems of the neuro-endocrine-immune networks are involved in the actions of acupuncture in the improvement of IR.In the future,more attention should be paid to the study on the acupoint specificity,suitable acupoint combinations and stimulus parameters in clinical treatment of IR related various metabolic diseases,further optimizing clinical treatment protocols.
Insulin resistance(IR)is a common pathophysiological basis of many chronic diseases,such as obesity,type2 diabetes mellitus(T2 DM),nonalcoholic fatty liver disease,cerebral vascular disease,cardiovascular and neurodegenerative diseases,etc.Acupuncture therapy has been demonstrated to have a positive role in reducing IR level in clinical practice.In the present paper,we summarized development of researches on the mechanism of acupuncture therapy underlying improvement of IR in recent 10 years from 1)regulating expression of hypothalamic phosphatidylinositol-3-kinase(PI3 K)-p85 and PI3 K-P110 proteins in obesity rats;2)regulating the levels of some related proteins of insulin target tissues(liver and skeletal muscle),such as insulin receptor substrate-1(IRS)-1 and-2,glucose transporter mRNAs and proteins,sterol regulatory element-binding protein 1(SREBP-1)and fatty acid synthetase proteins;3)suppressing inflammatory reaction of liver tissue and down-regulating serum adiponectin in T2 DM rats;4)raising the activity of superoxide dismutase(SOD)and reducing the levels of reactive oxygen species,and malondialdehyde(MDA)contents of quadriceps femoris in spontaneous IR rats;and 5)attenuating structural injury of pancreas islet and apoptosis of pancreaticβcells in diabetes rats.Multi-levels and various systems of the neuro-endocrine-immune networks are involved in the actions of acupuncture in the improvement of IR.In the future,more attention should be paid to the study on the acupoint specificity,suitable acupoint combinations and stimulus parameters in clinical treatment of IR related various metabolic diseases,further optimizing clinical treatment protocols.
引文
[1]KIM C H,KIM H K,KIM E H,et al.Longitudinal changes in insulin resistance,beta-cell function,and glucose regulation status in prediabetes[J].Am J Med Sci,2018,355(1):54-60.
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[3]REGAZZETTI C,PERALDI P,GRMEAUX T,et al.Hypoxia decreases insulin signaling pathways in adipocytes[J].Diabetes,2009,58(1):95-103.
[4]LI J,NG E H,STENER-VICTORIN E,et al.Acupuncture treatment for insulin sensitivity of women with polycystic ovary syndrome and insulin resistance:a study protocol for a randomized controlled trial[J].Trials,2017,18(1):115.
[5]ZHENG Y,STENER-VICTORIN E,NG E H,et al.How does acupuncture affect insulin sensitivity in women with polycystic ovary syndrome and insulin resistance?Study protocol of a prospective pilot study[J].BMJ Open,2015,5(4):e007757.
[6]刘美君,刘志诚,徐斌.针灸治疗2型糖尿病640例临床疗效观察[J].中华中医药杂志,2015,30(12):4531-4533.
[7]张亚琴.针灸对肥胖型多囊卵巢综合征患者脂联素、瘦素及胰岛素抵抗的影响[J].中医学报,2017,32(11):2259-2262.
[8]KOSKINEN J,MAGNUSSEN C G,SABIN M A,et al.Youth overweight and metabolic disturbances in predicting carotid intima-media thickness,type 2diabetes,and metabolic syndrome in adulthood:the cardiovascular risk in young Finns study[J].Diabetes Care,2014,37(7):1870-1877.
[9]MORTON G J,CUMMINGS D E,BASKIN D G,et al.Central nervous system control of food intake and body weight[J].Nature,2006,443(7109):289-295.
[10]刘霞,何军锋,屈娅婷,等.电针对单纯性肥胖大鼠胰岛素抵抗及下丘脑胰岛素信号分子的影响[J].中国针灸,2016,36(9):957-961.
[11]王静芝,王华,周焕娇,等.电针对胰岛素抵抗大鼠下丘脑磷脂酰肌醇3激酶及磷脂酰肌醇3激酶催化亚基蛋白表达的影响[J].针刺研究,2014,39(1):46-51.
[12]DRAZNIN B.Molecular mechanisms of insulin resistance:serine phosphorylation of insulin receptor substrate-1and increased expression of p85alpha:the two sides of a coin[J].Diabetes,2006,55(8):2392-2397.
[13]SHIH C C,LIN C H,LIN W L,et al.Momordica charantia,extract on insulin resistance and the skeletal muscle GLUT4protein in fructose-fed rats[J].J Ethnopharmacol,2009,123(1):82-90.
[14]陈宏,张智龙,王栩,等.基于磷脂酰肌醇3激酶信号通路探究针刺对2型糖尿病大鼠胰岛素抵抗的影响[J].针刺研究,2017,42(3):197-201.
[15]SAVAGE D B,PETERSEN K F,SHULMAN G I.Disordered lipid metabolism and the pathogenesis of insulin resistance[J].Physiol Rev,2007,87(2):507-520.
[16]李媛媛,胡慧,梁翠梅,等.针刺“带脉”穴对代谢综合征大鼠体质量、血糖和脂代谢的影响[J].针刺研究,2014,39(3):202-206.
[17]李知行,张海华,蓝丹纯,等.电针对高脂诱导胰岛素抵抗大鼠肝脏固醇调节元件结合蛋白-1c、脂肪酸合成酶的影响[J].针刺研究,2018,43(1):8-13.
[18]SHOELSON S E,LEE J,GOLDFINE A B.Inflammation and insulin resistance[J].J Clin Invest,2006,116(7):1793-1801.
[19]SCHENK S,SABERI M,OLEFSKY J M.Insulin sensitivity:modulation by nutrients and inflammation[J].J Clin Invest,2008,118(9):2992-3002.
[20]黄振,阮继源.电针对实验性2型糖尿病大鼠胰岛素抵抗和瘦素的影响[J].中华中医药学刊,2012,30(10):2332-2335.
[21]李知行,蓝丹纯,张弘弢,等.电针对胰岛素抵抗大鼠肝脏AMPK及ACC蛋白表达的影响[J].辽宁中医杂志,2017,44(4):864-867.
[22]GOODARZI M T,NAVIDI A A,REZAEI M,et al.Oxidative damage to DNA and lipids:correlation with protein glycation in patients with type 1diabetes[J].J Clin Lab Anal,2010,24(2):72-76.
[23]DOKKEN B B,SAENGSIRISUWAN V,KIM J S,et al.Oxidative stress-induced insulin resistance in rat skeletal muscle:role of glycogen synthase kinase-3[J].Am J Physiol Endocrinol Metab,2008,294(3):E615-621.
[24]BOKOV A,CHAUDHURI A,RICHARDSON A.The role of oxidative damage and stress in aging[J].Mech Ageing Dev,2004,125(10-11):811-826.
[25]徐芬.电针对ZDR大鼠股四头肌PGC-1α及下游线粒体相关基因表达的影响[D].武汉:湖北中医药大学,2015.
[26]WEIR G C,BONNER-WEIR S.Isletβcell mass in diabetes and how it relates to function,birth,and death[J].Ann N YAcad Sci,2013,1281(1):92-105.
[27]王栩,张智龙,杨元庆,等.针刺对2型糖尿病大鼠胰岛素抵抗及胰岛β细胞形态学的影响[J].南京中医药大学学报,2016,32(1):45-49.
[28]肖会,覃健,杜一鹏,等.穴位埋线抑制2型糖尿病胰岛β细胞凋亡的实验研究[J].辽宁中医药大学学报,2011,13(10):254-256.
[29]金炳旭,赖新生,唐纯志.腧穴特异性研究进展[J].针刺研究,2008,33(2):135-138.
[30]张文奎,刘艳平,孙志.针刺脾经不同腧穴对2型糖尿病模型小鼠血脂水平的影响[J].江苏中医药,2015,47(8):74-75.
[31]李知行,蓝丹纯,张海华,等.基于数据挖掘的针灸治疗胰岛素抵抗用穴规律研究[J].针刺研究,2016,41(6):545-549.
[32]张国雪,刘昊,王富春.论腧穴配伍与针灸处方[J].中国针灸,2014,34(10):987-990.
[33]张海燕,秦黎虹,汪泓.电针不同刺激参数对单纯性肥胖患者减肥效应与胰岛素抵抗的影响临床观察[J].中国医学创新,2012,15(9):6-8.
[34]黄志真,梁凤霞,王华.不同强度针刺对糖尿病大鼠肝脏GLUT4mRNA的影响[J].中华中医药学刊,2008,26(2):427-429.
[35]ZHANG Y,QIN W,LIU P,et al.An fMRI study of acupuncture using independent component analysis[J].Neurosci Lett,2009,449(1):6-9.
[2]SHI Z.Prevalence of diabetes among men and women in China[J].N Engl J Med,2010,362(25):2425.
[3]REGAZZETTI C,PERALDI P,GRMEAUX T,et al.Hypoxia decreases insulin signaling pathways in adipocytes[J].Diabetes,2009,58(1):95-103.
[4]LI J,NG E H,STENER-VICTORIN E,et al.Acupuncture treatment for insulin sensitivity of women with polycystic ovary syndrome and insulin resistance:a study protocol for a randomized controlled trial[J].Trials,2017,18(1):115.
[5]ZHENG Y,STENER-VICTORIN E,NG E H,et al.How does acupuncture affect insulin sensitivity in women with polycystic ovary syndrome and insulin resistance?Study protocol of a prospective pilot study[J].BMJ Open,2015,5(4):e007757.
[6]刘美君,刘志诚,徐斌.针灸治疗2型糖尿病640例临床疗效观察[J].中华中医药杂志,2015,30(12):4531-4533.
[7]张亚琴.针灸对肥胖型多囊卵巢综合征患者脂联素、瘦素及胰岛素抵抗的影响[J].中医学报,2017,32(11):2259-2262.
[8]KOSKINEN J,MAGNUSSEN C G,SABIN M A,et al.Youth overweight and metabolic disturbances in predicting carotid intima-media thickness,type 2diabetes,and metabolic syndrome in adulthood:the cardiovascular risk in young Finns study[J].Diabetes Care,2014,37(7):1870-1877.
[9]MORTON G J,CUMMINGS D E,BASKIN D G,et al.Central nervous system control of food intake and body weight[J].Nature,2006,443(7109):289-295.
[10]刘霞,何军锋,屈娅婷,等.电针对单纯性肥胖大鼠胰岛素抵抗及下丘脑胰岛素信号分子的影响[J].中国针灸,2016,36(9):957-961.
[11]王静芝,王华,周焕娇,等.电针对胰岛素抵抗大鼠下丘脑磷脂酰肌醇3激酶及磷脂酰肌醇3激酶催化亚基蛋白表达的影响[J].针刺研究,2014,39(1):46-51.
[12]DRAZNIN B.Molecular mechanisms of insulin resistance:serine phosphorylation of insulin receptor substrate-1and increased expression of p85alpha:the two sides of a coin[J].Diabetes,2006,55(8):2392-2397.
[13]SHIH C C,LIN C H,LIN W L,et al.Momordica charantia,extract on insulin resistance and the skeletal muscle GLUT4protein in fructose-fed rats[J].J Ethnopharmacol,2009,123(1):82-90.
[14]陈宏,张智龙,王栩,等.基于磷脂酰肌醇3激酶信号通路探究针刺对2型糖尿病大鼠胰岛素抵抗的影响[J].针刺研究,2017,42(3):197-201.
[15]SAVAGE D B,PETERSEN K F,SHULMAN G I.Disordered lipid metabolism and the pathogenesis of insulin resistance[J].Physiol Rev,2007,87(2):507-520.
[16]李媛媛,胡慧,梁翠梅,等.针刺“带脉”穴对代谢综合征大鼠体质量、血糖和脂代谢的影响[J].针刺研究,2014,39(3):202-206.
[17]李知行,张海华,蓝丹纯,等.电针对高脂诱导胰岛素抵抗大鼠肝脏固醇调节元件结合蛋白-1c、脂肪酸合成酶的影响[J].针刺研究,2018,43(1):8-13.
[18]SHOELSON S E,LEE J,GOLDFINE A B.Inflammation and insulin resistance[J].J Clin Invest,2006,116(7):1793-1801.
[19]SCHENK S,SABERI M,OLEFSKY J M.Insulin sensitivity:modulation by nutrients and inflammation[J].J Clin Invest,2008,118(9):2992-3002.
[20]黄振,阮继源.电针对实验性2型糖尿病大鼠胰岛素抵抗和瘦素的影响[J].中华中医药学刊,2012,30(10):2332-2335.
[21]李知行,蓝丹纯,张弘弢,等.电针对胰岛素抵抗大鼠肝脏AMPK及ACC蛋白表达的影响[J].辽宁中医杂志,2017,44(4):864-867.
[22]GOODARZI M T,NAVIDI A A,REZAEI M,et al.Oxidative damage to DNA and lipids:correlation with protein glycation in patients with type 1diabetes[J].J Clin Lab Anal,2010,24(2):72-76.
[23]DOKKEN B B,SAENGSIRISUWAN V,KIM J S,et al.Oxidative stress-induced insulin resistance in rat skeletal muscle:role of glycogen synthase kinase-3[J].Am J Physiol Endocrinol Metab,2008,294(3):E615-621.
[24]BOKOV A,CHAUDHURI A,RICHARDSON A.The role of oxidative damage and stress in aging[J].Mech Ageing Dev,2004,125(10-11):811-826.
[25]徐芬.电针对ZDR大鼠股四头肌PGC-1α及下游线粒体相关基因表达的影响[D].武汉:湖北中医药大学,2015.
[26]WEIR G C,BONNER-WEIR S.Isletβcell mass in diabetes and how it relates to function,birth,and death[J].Ann N YAcad Sci,2013,1281(1):92-105.
[27]王栩,张智龙,杨元庆,等.针刺对2型糖尿病大鼠胰岛素抵抗及胰岛β细胞形态学的影响[J].南京中医药大学学报,2016,32(1):45-49.
[28]肖会,覃健,杜一鹏,等.穴位埋线抑制2型糖尿病胰岛β细胞凋亡的实验研究[J].辽宁中医药大学学报,2011,13(10):254-256.
[29]金炳旭,赖新生,唐纯志.腧穴特异性研究进展[J].针刺研究,2008,33(2):135-138.
[30]张文奎,刘艳平,孙志.针刺脾经不同腧穴对2型糖尿病模型小鼠血脂水平的影响[J].江苏中医药,2015,47(8):74-75.
[31]李知行,蓝丹纯,张海华,等.基于数据挖掘的针灸治疗胰岛素抵抗用穴规律研究[J].针刺研究,2016,41(6):545-549.
[32]张国雪,刘昊,王富春.论腧穴配伍与针灸处方[J].中国针灸,2014,34(10):987-990.
[33]张海燕,秦黎虹,汪泓.电针不同刺激参数对单纯性肥胖患者减肥效应与胰岛素抵抗的影响临床观察[J].中国医学创新,2012,15(9):6-8.
[34]黄志真,梁凤霞,王华.不同强度针刺对糖尿病大鼠肝脏GLUT4mRNA的影响[J].中华中医药学刊,2008,26(2):427-429.
[35]ZHANG Y,QIN W,LIU P,et al.An fMRI study of acupuncture using independent component analysis[J].Neurosci Lett,2009,449(1):6-9.