基于PI3K/Akt通路的中药治疗糖尿病研究进展
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摘要
糖尿病是一组以高血糖为特征的代谢性疾病,发病率极高,并发症较多,目前已成为世界范围内日益严重的公共健康问题,严重影响人民的生活质量。磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)信号通路是胰岛素信号转导的主要途径,也是调控血糖的主要信号通道,其信号分子的异常可引起信号转导途径异常,从而影响相应组织器官细胞的增殖、凋亡、转移和侵袭,导致疾病的发生。研究PI3K/Akt信号通道对于考察中药是否具有明确而稳定的降血糖作用具有积极的意义。目前,治疗糖尿病的中药、西药相对较多,但多数药物尤其是西药对于并发症的控制相对较差,为了解中药在治疗糖尿病方面的进展,以期更好地研究中药在糖尿病方面的综合治疗作用及机制,进一步发挥中医药在糖尿病治疗方面的多靶点、多途径、多通道、标本兼治的优势与特色,本文就近年来基于PI3K/Akt信号通路的中药治疗糖尿病体内、外研究进行了较为系统的分析,包括基于该信号通道的对糖尿病产生直接原因的胰岛素分泌的影响、对胰岛素3个主要靶器官(肝、骨骼肌、脂肪)及对糖尿病4个主要并发症相应部位(脑、肾、心、睾丸)的影响,也为研究中药单味药及复方的降血糖机制研究提供一定的思路及指导。
Diabetes mellitus(DM) is a metabolic disease characterized by hyperglycemia,with a high incidence and many complications. It has become an increasingly serious public health problem in the world,and has seriously affected the quality of life. Phosphatidylinositol-3-kinases(PI3 K)/protein kinase B(Akt) signaling pathway is the main pathway of insulin signal transmission and the main signal channel for regulating blood glucose.The abnormal signal molecule of PI3 K/Akt may cause abnormal signal transduction pathway,so as to impact the proliferation,apoptosis,metastasis and invasion of the corresponding tissues and organs,and lead to the occurrence of disease. Study of PI3 K/Akt signal channel has a positive significance for investigating whether traditional Chinese medicine(TCM) has a definite and stable hypoglycemic effect. Currently,there are many TCM and Western medicines to treat diabetes,however,most drugs,especially Western medicines,have a relatively poor effect in controlling complications. To understand the progress of TCM in treatment of diabetes,in expectation of better studying the comprehensive therapeutic effect and mechanism of TCM on diabetes,and further developing the multi-target,multi-way and multi-channel advantages and features of TCM in the treatment of diabetes,this paper focuses on a systematic analysis on the progress of in vivo and in vitro studies on DM based on PI3 K/Akt signaling channel in recent years,including the effect of the signaling channel on insulin secretion,the three main target organs of insulin(liver,skeletal muscle and fat),and its effect on the four main complications of diabetes(brain,kidney,heart,testis),and also provides certain ideas and guidance for the study of hypoglycemic mechanism of TCM monomer,TCM and compound medicine.
Diabetes mellitus(DM) is a metabolic disease characterized by hyperglycemia,with a high incidence and many complications. It has become an increasingly serious public health problem in the world,and has seriously affected the quality of life. Phosphatidylinositol-3-kinases(PI3 K)/protein kinase B(Akt) signaling pathway is the main pathway of insulin signal transmission and the main signal channel for regulating blood glucose.The abnormal signal molecule of PI3 K/Akt may cause abnormal signal transduction pathway,so as to impact the proliferation,apoptosis,metastasis and invasion of the corresponding tissues and organs,and lead to the occurrence of disease. Study of PI3 K/Akt signal channel has a positive significance for investigating whether traditional Chinese medicine(TCM) has a definite and stable hypoglycemic effect. Currently,there are many TCM and Western medicines to treat diabetes,however,most drugs,especially Western medicines,have a relatively poor effect in controlling complications. To understand the progress of TCM in treatment of diabetes,in expectation of better studying the comprehensive therapeutic effect and mechanism of TCM on diabetes,and further developing the multi-target,multi-way and multi-channel advantages and features of TCM in the treatment of diabetes,this paper focuses on a systematic analysis on the progress of in vivo and in vitro studies on DM based on PI3 K/Akt signaling channel in recent years,including the effect of the signaling channel on insulin secretion,the three main target organs of insulin(liver,skeletal muscle and fat),and its effect on the four main complications of diabetes(brain,kidney,heart,testis),and also provides certain ideas and guidance for the study of hypoglycemic mechanism of TCM monomer,TCM and compound medicine.
引文
[1]纪立伟,郭立新.糖尿病治疗临床药物指导手册[M].北京:人民卫生出版社,2014:10.
[2] Guariguata L,Whiting D R,Hambleton I,et al. Global estimates of diabetes prevalence in adults for 2013 and projections for 2035[J]. Diabetes Res Clin Pract,2014,103(2):137-149.
[3] HUANG X J,LIU G H,GUO J,et al. The PI3K/Akt pathway in obesity and type 2 diabetes[J]. Int J Biol Sci,2018,14(11):1483-1496.
[4] Fruman D A,Rommel C. PI3K and cancer:lessons,challenges and opportunities[J]. Nat Rev Drug Discov,2014,13(2):140-156.
[5] Velazquez-Garcia S,Valle S,Rosa T C,et al. Activation of protein kinase C-ζin pancreaticβ-cells in vivo improves glucose tolerance and inducesβ-cell expansion via m TOR activation[J]. Diabetes,2011,60(10):2546-2559.
[6]刘美晓,孙一婵,侯丽娜,等.丝胶对2型糖尿病大鼠胰腺胰岛素PI3K-Akt信号通路的调节作用[J].解剖学报,2016,47(6):807-811.
[7]王恩芳,刘曙玮.番茄红素通过激活PI3K/Akt信号通路对2型糖尿病小鼠治疗机制研究[J].实用糖尿病杂志,2015,11(5):35-37.
[8]杨萍.白背三七的体内降血糖作用及其对小鼠Akt/PI3K信号通路的影响[D].苏州:苏州大学,2015.
[9]周琦,朱向东,仝小林,等.葛根芩连汤对2型糖尿病模型大鼠胰岛细胞IRS-2/PI3K-Akt通路的影响[J].中医杂志,2018,59(11):973-977.
[10] Titchenell P M,Quinn W J,LU M,et al. Direct hepatocyte insulin signaling is required for lipogenesis but is dispensable for the suppression of glucose production[J]. Cell Metab,2016,23(6):1154-1166.
[11] WANG J,WANG C,LI S,et al. Anti-diabetic effects of Inonotusobliquus polysaccharides in streptozotocininduced type 2 diabetic mice and potential mechanism via PI3K-Akt signalpathway[J]. Biomed Pharmacother,2017,95(10):1669-1677.
[12]徐源,黄存东,李竹青,等.黄芪甲苷对糖尿病大鼠肝损伤保护作用及其机制研究[J].安徽医科大学学报,2017,52(12):1823-1829.
[13]林彩霞.青钱柳双瓜袋泡茶对2型糖尿病大鼠降糖降脂作用及其机制研究[D].南宁:广西医科大学,2018.
[14]刘贝,孙建平,赵阳,等.明日叶查尔酮对糖尿病大鼠肝细胞PI3K和Akt mRNA表达的影响[J].卫生研究,2013,42(3):466-469.
[15]刘颐轩,臧莎莎,宋光耀,等.津力达对胰岛素抵抗大鼠肝脏PI3K/Akt信号通路的影响[J].中国实验方剂学杂志,2015,21(12):72-76.
[16]邢瑞.六味地黄汤对2型糖尿病大鼠的干预作用及对PI3KP110、Akt蛋白磷酸化水平的影响[D].长沙:湖南中医药大学,2014.
[17]隋艳波,刘莉,谢宁.洋参御糖丸调控糖尿病大鼠肝脏胰岛素PI3K信号通路的机制研究[J].河南中医,2014,34(1):49-51.
[18]蔡羽.桑瓜饮干预2型糖尿病大鼠的作用及其PI3K/Akt信号通路机制研究[D].武汉:湖北中医药大学,2018.
[19]李中南,方朝晖,熊园园,等.丹蛭降糖胶囊对糖尿病大鼠肝脏PI3K/Akt信号通路的影响[J].上海中医药杂志,2015,49(9):67-70.
[20]张先慧,胡照娟,张艳红,等.辛开苦降方对初发2型糖尿病KKay小鼠肝脏胰岛素抵抗及IRS-2/PI3K通路的影响(英文)[J].中华中医药杂志,2015,30(5):1774-1779.
[21]吴天宸.岩藻黄素降血糖机理的研究[D].天津:天津科技大学,2016.
[22]张继媛.三种植物提取物联合改善2型糖尿病小鼠糖脂代谢效果及对肠道菌群的影响研究[D].天津:天津农学院,2017.
[23] FAN Y,HE Z W,WANG W,et al. Tangganjian decoction ameliorates type 2 diabetes mellitus and nonalcoholic fatty liver disease in rats by activating the IRS/PI3K/Akt signaling pathway[J]. Biomed Pharmacother,2018,106(9):733-737.
[24] YAN J,WANG C,JIN Y,et al. Catalpol ameliorates hepatic insulin resistance in type 2 diabetes through acting on AMPK/NOX4/PI3K/Akt pathway[J].Pharmacol Res,2017,130(12):466-480.
[25] SHAN G,GUO Q,QIN C G,et al. Sea buckthorn fruit oil extract alleviates insulin resistance through the PI3K/Akt signaling pathway in type 2 diabetes mellitus cells and rats[J]. J Agr Food Chem,2017,65(7):1328-1336.
[26] Choi J,Kim K J,Koh E J,et al. Gelidiumelegans extract ameliorates type 2 diabetes via regulation of MARK and PI3K/Akt signaling[J]. Nutrients,2018,10(1):51-64.
[27] SONG C J,LIU D H,YANG S H,et al. Sericin enhances the insulin PI3K/Akt signaling pathway in the liver of a type 2 diabetes rat model[J]. Exp Ther Med,2018,16(4):3345-3352.
[28] Kraegen E W,James D E,Jenkins A B,et al. Doseresponse curves for in vivo insulin sensitivity in individual tissues in rats[J]. Am J Physiol,1985,248(3/1):353-362.
[29]张茁,孙文,刘铜华,等.山柰酚对2型糖尿病小鼠骨骼肌PI3K-Akt-GLUT4信号通路的影响[J].世界科学技术-中医药现代化,2016,18(7):1139-1143.
[30]洪金妮,黎巍威,张宁,等.中药降糖复方水提取物对KK-Ay糖尿病小鼠骨骼肌糖代谢PI3K/Akt信号通路的影响[J].药物评价研究,2017,40(10):1397-1401.
[31]师林,杨玉彬,黄颖娟,等.健脾化湿方对脾虚痰湿型肥胖2型糖尿病胰岛素抵抗大鼠骨骼肌PI3K/Akt通路的影响[J].中华中医药杂志,2018,33(2):530-534.
[32]钟文,谢春光,朱海燕,等.参芪复方介导IGF-1/PI3K/Akt通路干预糖尿病大鼠骨骼肌病变的实验研究[J].辽宁中医杂志,2018,45(5):1072-1075,1118.
[33]陈璇,徐凛峰,汪悦,等.白虎二地汤改善2型糖尿病大鼠胰岛素抵抗分子机制的研究[J].南京中医药大学学报,2015,31(4):364-367.
[34] Kubota T,Kubota N,Kadowaki T. Imbalanced insulin actions in obesity and type 2 diabetes:key mouse models of insulin signaling pathway[J]. Cell Metab,2017,25(4):797-810.
[35] WANG J B,HU X Q,AI W,et al. Phytol increases adipocyte number and glucose tolerance through activation of PI3K/Akt signaling pathway in mice fed high-fat and high-fructose diet[J]. Biochem Bioph Res Co,2017,489(4):432-438.
[36]戴冰,吴沁璇,肖子曾,等.六味地黄汤及其水提醇溶部位对2型糖尿病模型大鼠脂肪组织中PI3K/Akt信号通路的影响[J].中成药,2016,38(2):428-430.
[37]葛惠娜.紫檀芪对2型糖尿病大鼠糖脂代谢的影响[D].郑州:郑州大学,2018.
[38]谢宁,关慧波,侯淑峰,等.正交实验法优选洋参御糖丸最佳水提工艺研究[J].中华中医药学刊,2007,25(12):2446-2447.
[39]隋艳波,刘莉,谢宁.洋参御糖丸对糖尿病大鼠脂肪组织PI3K信号通路的调控作用[J].中医药学报,2013,41(3):85-87.
[40] LI W,Risacher S L,HUANG E,et al. Type 2 diabetes mellitus is associated with brain atrophy and hypometabolism in the ADNI cohort[J]. Neurology,2016,87(6):595-600.
[41] ZHOU X,WANG S,DING X,et al. Zeaxanthin improves diabetes-induced cognitive deficit in rats through activiting PI3K/Akt signaling pathway[J]. Brain Res Bull,2017,132(6):190-198.
[42]毛小元,周宏灏,刘昭前.蛇床子素通过抑制PI3K/Akt信号通路减轻糖尿病脑病的炎症反应[J].中国老年学杂志,2015,35(17):4743-4746.
[43]师林,柯斌,杨玉彬,等.加味苓桂术甘汤联合限食对脾虚痰湿型糖尿病脑病大鼠海马组织PI3K/Akt/m TOR通路的影响[J].中药材,2018,41(5):1187-1191.
[44]王耕银. PI3K/Akt/GSK-3β通路在莱菔硫烷调控糖尿病大鼠认知功能减退中的作用[D].石家庄:河北医科大学,2017.
[45]王永胜,杨丽霞,程涛,等.糖尿病肾病的炎症致病机制与中药防治[J].中国实验方剂学杂志,2018,24(2):200-207.
[46]杨辰,尹德海,朴元林,等.黄芪菟箭合剂对糖尿病大鼠肾脏PI3K-Akt-mTOR信号通路的影响[J].中国中西医结合肾病杂志,2016,17(10):862-866,944.
[47]刘颖.基于PI3K/m TOR通路研究通心络对STZ糖尿病大鼠肾脏的保护作用[D].锦州:锦州医科大学,2018.
[48]童楠,张宁.中药益肾颗粒通过PI3K/Akt/m TOR和LKB1/AMPK/Sirt1信号通路对糖尿病肾病大鼠的干预作用研究[J].中华中医药杂志,2018,33(5):1853-1857.
[49]张雅琴,李小宁,吴萍萍,等.苦瓜皂苷对糖尿病肾病PI3K/Akt信号通路的影响[J].江苏医药,2015,41(7):750-753,869.
[50]苏衍进,王郁金,王琴,等.糖肾一号胶囊对糖尿病肾病大鼠的作用及其机制研究[J].中草药,2017,48(19):4011-4016.
[51] HUANG W J,FU Q,XIAO Y H,et al. Effect of qufengtongluo decoction on PI3K/Akt signaling pathway in the kidney of type 2 diabetes mellitus rat(GK Rat)with diabetic nephropathy[J]. Evid-Based Compl Alt,2018,2018(9):1-9.
[52]吴学敏,唐新征,刘学耀.益气化瘀法对糖尿病肾病大鼠PI3K/Akt通路影响的实验研究[J].四川中医,2016,34(1):48-51.
[53]杨晶晶.基于胰岛素抵抗IRS1/PI3K/Akt信号途径探讨黄葵胶囊改善糖尿病肾病足细胞损伤的作用和机制[D].南京:南京中医药大学,2017.
[54]王颖超.基于“肾痿”假说的糖肾平对DKD大鼠肾脏保护作用及PI3K/Akt信号转导通路影响的研究[D].北京:北京中医药大学,2014.
[55]薛建军,范强,杨丽霞,等.糖尿病心肌病发病机制及中医药治疗概述[J].中国实验方剂学杂志,2017,23(22):211-217.
[56]闫文娜.荞麦花叶总黄酮对2型糖尿病大鼠心肌损伤及PI3K的影响[D].石家庄:河北联合大学,2014.
[57] Al-Roujeaie A S,Abuohashish H M,Ahmed M M,et al.Effect of rutin on diabetic-induced erectile dysfunction:Possible involvement of testicular biomarkers in male rats[J]. Andrologia,2017,49(8):e12737.
[58] SHI G J,ZHENG J,HAN X X,et al. Lycium barbarum,polysaccharide attenuates diabetic testicular dysfunction via inhibition of the PI3K/Akt pathway-mediated abnormal autophagy in male mice[J]. Cell Tissue Res,2018,374(3):653-666.
[59]龚又明,郑显辉,谢鸣坤,等.小檗碱对Hep G2胰岛素抵抗细胞PI3K/Akt1/GLUT1信号通路的调控作用[J].新中医,2017,49(8):1-4.
[60]李蕾,苏妍文,李宇晴,等.明日叶查尔酮对胰岛素抵抗细胞PI3K-Akt-GLUT4信号通路的影响[J].卫生研究,2017,46(4):669-671,674.
[61] Ogurtsova K,da Rocha Fernandes JD,HUANG Y,et al.IDF Diabetes Atlas:global estimates for the prevalence of diabetes for 2015 and 2040[J]. Diabetes Res Clin Pract,2017,doi:10. 10161j. diabres. 2017. 03. 024.
[62] Beagley J,Guariguata L,Weil C,et al. Global estimates of undiagnosed diabetes in adults[J]. Diabetes Res Clin Pract,2014,103(2):150-160.
[63]王笑,王甄真,陈雁. PI3K/Akt信号通路在维持血糖平衡中的作用[J].生命科学,2013,25(2):133-139.
[2] Guariguata L,Whiting D R,Hambleton I,et al. Global estimates of diabetes prevalence in adults for 2013 and projections for 2035[J]. Diabetes Res Clin Pract,2014,103(2):137-149.
[3] HUANG X J,LIU G H,GUO J,et al. The PI3K/Akt pathway in obesity and type 2 diabetes[J]. Int J Biol Sci,2018,14(11):1483-1496.
[4] Fruman D A,Rommel C. PI3K and cancer:lessons,challenges and opportunities[J]. Nat Rev Drug Discov,2014,13(2):140-156.
[5] Velazquez-Garcia S,Valle S,Rosa T C,et al. Activation of protein kinase C-ζin pancreaticβ-cells in vivo improves glucose tolerance and inducesβ-cell expansion via m TOR activation[J]. Diabetes,2011,60(10):2546-2559.
[6]刘美晓,孙一婵,侯丽娜,等.丝胶对2型糖尿病大鼠胰腺胰岛素PI3K-Akt信号通路的调节作用[J].解剖学报,2016,47(6):807-811.
[7]王恩芳,刘曙玮.番茄红素通过激活PI3K/Akt信号通路对2型糖尿病小鼠治疗机制研究[J].实用糖尿病杂志,2015,11(5):35-37.
[8]杨萍.白背三七的体内降血糖作用及其对小鼠Akt/PI3K信号通路的影响[D].苏州:苏州大学,2015.
[9]周琦,朱向东,仝小林,等.葛根芩连汤对2型糖尿病模型大鼠胰岛细胞IRS-2/PI3K-Akt通路的影响[J].中医杂志,2018,59(11):973-977.
[10] Titchenell P M,Quinn W J,LU M,et al. Direct hepatocyte insulin signaling is required for lipogenesis but is dispensable for the suppression of glucose production[J]. Cell Metab,2016,23(6):1154-1166.
[11] WANG J,WANG C,LI S,et al. Anti-diabetic effects of Inonotusobliquus polysaccharides in streptozotocininduced type 2 diabetic mice and potential mechanism via PI3K-Akt signalpathway[J]. Biomed Pharmacother,2017,95(10):1669-1677.
[12]徐源,黄存东,李竹青,等.黄芪甲苷对糖尿病大鼠肝损伤保护作用及其机制研究[J].安徽医科大学学报,2017,52(12):1823-1829.
[13]林彩霞.青钱柳双瓜袋泡茶对2型糖尿病大鼠降糖降脂作用及其机制研究[D].南宁:广西医科大学,2018.
[14]刘贝,孙建平,赵阳,等.明日叶查尔酮对糖尿病大鼠肝细胞PI3K和Akt mRNA表达的影响[J].卫生研究,2013,42(3):466-469.
[15]刘颐轩,臧莎莎,宋光耀,等.津力达对胰岛素抵抗大鼠肝脏PI3K/Akt信号通路的影响[J].中国实验方剂学杂志,2015,21(12):72-76.
[16]邢瑞.六味地黄汤对2型糖尿病大鼠的干预作用及对PI3KP110、Akt蛋白磷酸化水平的影响[D].长沙:湖南中医药大学,2014.
[17]隋艳波,刘莉,谢宁.洋参御糖丸调控糖尿病大鼠肝脏胰岛素PI3K信号通路的机制研究[J].河南中医,2014,34(1):49-51.
[18]蔡羽.桑瓜饮干预2型糖尿病大鼠的作用及其PI3K/Akt信号通路机制研究[D].武汉:湖北中医药大学,2018.
[19]李中南,方朝晖,熊园园,等.丹蛭降糖胶囊对糖尿病大鼠肝脏PI3K/Akt信号通路的影响[J].上海中医药杂志,2015,49(9):67-70.
[20]张先慧,胡照娟,张艳红,等.辛开苦降方对初发2型糖尿病KKay小鼠肝脏胰岛素抵抗及IRS-2/PI3K通路的影响(英文)[J].中华中医药杂志,2015,30(5):1774-1779.
[21]吴天宸.岩藻黄素降血糖机理的研究[D].天津:天津科技大学,2016.
[22]张继媛.三种植物提取物联合改善2型糖尿病小鼠糖脂代谢效果及对肠道菌群的影响研究[D].天津:天津农学院,2017.
[23] FAN Y,HE Z W,WANG W,et al. Tangganjian decoction ameliorates type 2 diabetes mellitus and nonalcoholic fatty liver disease in rats by activating the IRS/PI3K/Akt signaling pathway[J]. Biomed Pharmacother,2018,106(9):733-737.
[24] YAN J,WANG C,JIN Y,et al. Catalpol ameliorates hepatic insulin resistance in type 2 diabetes through acting on AMPK/NOX4/PI3K/Akt pathway[J].Pharmacol Res,2017,130(12):466-480.
[25] SHAN G,GUO Q,QIN C G,et al. Sea buckthorn fruit oil extract alleviates insulin resistance through the PI3K/Akt signaling pathway in type 2 diabetes mellitus cells and rats[J]. J Agr Food Chem,2017,65(7):1328-1336.
[26] Choi J,Kim K J,Koh E J,et al. Gelidiumelegans extract ameliorates type 2 diabetes via regulation of MARK and PI3K/Akt signaling[J]. Nutrients,2018,10(1):51-64.
[27] SONG C J,LIU D H,YANG S H,et al. Sericin enhances the insulin PI3K/Akt signaling pathway in the liver of a type 2 diabetes rat model[J]. Exp Ther Med,2018,16(4):3345-3352.
[28] Kraegen E W,James D E,Jenkins A B,et al. Doseresponse curves for in vivo insulin sensitivity in individual tissues in rats[J]. Am J Physiol,1985,248(3/1):353-362.
[29]张茁,孙文,刘铜华,等.山柰酚对2型糖尿病小鼠骨骼肌PI3K-Akt-GLUT4信号通路的影响[J].世界科学技术-中医药现代化,2016,18(7):1139-1143.
[30]洪金妮,黎巍威,张宁,等.中药降糖复方水提取物对KK-Ay糖尿病小鼠骨骼肌糖代谢PI3K/Akt信号通路的影响[J].药物评价研究,2017,40(10):1397-1401.
[31]师林,杨玉彬,黄颖娟,等.健脾化湿方对脾虚痰湿型肥胖2型糖尿病胰岛素抵抗大鼠骨骼肌PI3K/Akt通路的影响[J].中华中医药杂志,2018,33(2):530-534.
[32]钟文,谢春光,朱海燕,等.参芪复方介导IGF-1/PI3K/Akt通路干预糖尿病大鼠骨骼肌病变的实验研究[J].辽宁中医杂志,2018,45(5):1072-1075,1118.
[33]陈璇,徐凛峰,汪悦,等.白虎二地汤改善2型糖尿病大鼠胰岛素抵抗分子机制的研究[J].南京中医药大学学报,2015,31(4):364-367.
[34] Kubota T,Kubota N,Kadowaki T. Imbalanced insulin actions in obesity and type 2 diabetes:key mouse models of insulin signaling pathway[J]. Cell Metab,2017,25(4):797-810.
[35] WANG J B,HU X Q,AI W,et al. Phytol increases adipocyte number and glucose tolerance through activation of PI3K/Akt signaling pathway in mice fed high-fat and high-fructose diet[J]. Biochem Bioph Res Co,2017,489(4):432-438.
[36]戴冰,吴沁璇,肖子曾,等.六味地黄汤及其水提醇溶部位对2型糖尿病模型大鼠脂肪组织中PI3K/Akt信号通路的影响[J].中成药,2016,38(2):428-430.
[37]葛惠娜.紫檀芪对2型糖尿病大鼠糖脂代谢的影响[D].郑州:郑州大学,2018.
[38]谢宁,关慧波,侯淑峰,等.正交实验法优选洋参御糖丸最佳水提工艺研究[J].中华中医药学刊,2007,25(12):2446-2447.
[39]隋艳波,刘莉,谢宁.洋参御糖丸对糖尿病大鼠脂肪组织PI3K信号通路的调控作用[J].中医药学报,2013,41(3):85-87.
[40] LI W,Risacher S L,HUANG E,et al. Type 2 diabetes mellitus is associated with brain atrophy and hypometabolism in the ADNI cohort[J]. Neurology,2016,87(6):595-600.
[41] ZHOU X,WANG S,DING X,et al. Zeaxanthin improves diabetes-induced cognitive deficit in rats through activiting PI3K/Akt signaling pathway[J]. Brain Res Bull,2017,132(6):190-198.
[42]毛小元,周宏灏,刘昭前.蛇床子素通过抑制PI3K/Akt信号通路减轻糖尿病脑病的炎症反应[J].中国老年学杂志,2015,35(17):4743-4746.
[43]师林,柯斌,杨玉彬,等.加味苓桂术甘汤联合限食对脾虚痰湿型糖尿病脑病大鼠海马组织PI3K/Akt/m TOR通路的影响[J].中药材,2018,41(5):1187-1191.
[44]王耕银. PI3K/Akt/GSK-3β通路在莱菔硫烷调控糖尿病大鼠认知功能减退中的作用[D].石家庄:河北医科大学,2017.
[45]王永胜,杨丽霞,程涛,等.糖尿病肾病的炎症致病机制与中药防治[J].中国实验方剂学杂志,2018,24(2):200-207.
[46]杨辰,尹德海,朴元林,等.黄芪菟箭合剂对糖尿病大鼠肾脏PI3K-Akt-mTOR信号通路的影响[J].中国中西医结合肾病杂志,2016,17(10):862-866,944.
[47]刘颖.基于PI3K/m TOR通路研究通心络对STZ糖尿病大鼠肾脏的保护作用[D].锦州:锦州医科大学,2018.
[48]童楠,张宁.中药益肾颗粒通过PI3K/Akt/m TOR和LKB1/AMPK/Sirt1信号通路对糖尿病肾病大鼠的干预作用研究[J].中华中医药杂志,2018,33(5):1853-1857.
[49]张雅琴,李小宁,吴萍萍,等.苦瓜皂苷对糖尿病肾病PI3K/Akt信号通路的影响[J].江苏医药,2015,41(7):750-753,869.
[50]苏衍进,王郁金,王琴,等.糖肾一号胶囊对糖尿病肾病大鼠的作用及其机制研究[J].中草药,2017,48(19):4011-4016.
[51] HUANG W J,FU Q,XIAO Y H,et al. Effect of qufengtongluo decoction on PI3K/Akt signaling pathway in the kidney of type 2 diabetes mellitus rat(GK Rat)with diabetic nephropathy[J]. Evid-Based Compl Alt,2018,2018(9):1-9.
[52]吴学敏,唐新征,刘学耀.益气化瘀法对糖尿病肾病大鼠PI3K/Akt通路影响的实验研究[J].四川中医,2016,34(1):48-51.
[53]杨晶晶.基于胰岛素抵抗IRS1/PI3K/Akt信号途径探讨黄葵胶囊改善糖尿病肾病足细胞损伤的作用和机制[D].南京:南京中医药大学,2017.
[54]王颖超.基于“肾痿”假说的糖肾平对DKD大鼠肾脏保护作用及PI3K/Akt信号转导通路影响的研究[D].北京:北京中医药大学,2014.
[55]薛建军,范强,杨丽霞,等.糖尿病心肌病发病机制及中医药治疗概述[J].中国实验方剂学杂志,2017,23(22):211-217.
[56]闫文娜.荞麦花叶总黄酮对2型糖尿病大鼠心肌损伤及PI3K的影响[D].石家庄:河北联合大学,2014.
[57] Al-Roujeaie A S,Abuohashish H M,Ahmed M M,et al.Effect of rutin on diabetic-induced erectile dysfunction:Possible involvement of testicular biomarkers in male rats[J]. Andrologia,2017,49(8):e12737.
[58] SHI G J,ZHENG J,HAN X X,et al. Lycium barbarum,polysaccharide attenuates diabetic testicular dysfunction via inhibition of the PI3K/Akt pathway-mediated abnormal autophagy in male mice[J]. Cell Tissue Res,2018,374(3):653-666.
[59]龚又明,郑显辉,谢鸣坤,等.小檗碱对Hep G2胰岛素抵抗细胞PI3K/Akt1/GLUT1信号通路的调控作用[J].新中医,2017,49(8):1-4.
[60]李蕾,苏妍文,李宇晴,等.明日叶查尔酮对胰岛素抵抗细胞PI3K-Akt-GLUT4信号通路的影响[J].卫生研究,2017,46(4):669-671,674.
[61] Ogurtsova K,da Rocha Fernandes JD,HUANG Y,et al.IDF Diabetes Atlas:global estimates for the prevalence of diabetes for 2015 and 2040[J]. Diabetes Res Clin Pract,2017,doi:10. 10161j. diabres. 2017. 03. 024.
[62] Beagley J,Guariguata L,Weil C,et al. Global estimates of undiagnosed diabetes in adults[J]. Diabetes Res Clin Pract,2014,103(2):150-160.
[63]王笑,王甄真,陈雁. PI3K/Akt信号通路在维持血糖平衡中的作用[J].生命科学,2013,25(2):133-139.
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