玉女煎治疗糖尿病及并发症研究进展

Therapeutic Effect of Yunüjian on Diabetes Mellitus and Its Complications:A Review

玉女煎出自《景岳全书》,由石膏、熟地黄、知母、麦冬和牛膝组成,主治“头痛,牙痛和消渴等属胃热阴虚证之疾病”。在现代临床应用中,玉女煎降糖疗效明确,能改善胰岛素抵抗,抑制氧化应激和炎症反应,并能降低雌激素水平,其组方灵活,形式多变,有玉女煎原方应用、玉女煎加减方应用、玉女煎与其他方剂合用(六味地黄汤、沙参麦冬汤、参芪散精汤、黄芪桂枝五物汤、增液汤、增液白虎汤等)、玉女煎与西药(胰岛素、二甲双胍、吡格列酮、糖适平等)联合应用。以玉女煎为基础的化裁方可用于2型糖尿病、妊娠期糖尿病、伴胰岛素抵抗的多囊卵巢综合征、糖尿病皮肤瘙痒症、糖尿病周围神经病变、糖尿病肾病、糖尿病酮症酸中毒、糖尿病视网膜病变和糖尿病牙周炎等的治疗。实验研究发现,玉女煎对胰岛β细胞的保护作用是改善糖尿病的重要途径,该方能通过提高自噬相关2B(Atg2B)、泛素样结合酶(Atg3)、γ-氨基丁酸受体相关蛋白(GABARAP)和选择性自噬蛋白(p62/SQSTM1)等的表达水平,清除受损的蛋白质和细胞器,同时可通过调节哺乳动物雷帕霉素靶蛋白(mTOR)和降低胰岛β细胞自噬基因(Beclin)的表达,进而在胰岛细胞增殖与凋亡过程中发挥积极作用,这些对维持胰岛细胞的数量结构和功能至关重要。玉女煎对生长激素释放肽(Ghrelin)、胃泌素(Gastrin)和促进生长激素促分泌素受体(GHSR)mRNA表达具有调控作用,同样也是发挥保护胰岛β细胞作用的重要途径。该文通过系统梳理玉女煎治疗糖尿病的临床与实验研究,论述玉女煎治疗糖尿病的作用机制,并就其中存在的问题提出建议,以期为临床应用玉女煎、挖掘玉女煎新用提供指导,对科学阐释玉女煎现代内涵,拓展其临床应用具有现实意义。

Yunüjian(Jing Yue’s Collected Works),composed of Gypsum Fibrosum,Rehmanniae Radix Praeparata,Anemarrhenae Rhizoma,Ophiopogonis Radix,and Achyranthis Bidentatae Radix,is used for the treatment of "headache,toothache,consumptive thirst,and other diseases caused by heat and Yin deficiency in the stomach".In modern clinical settings,it has definite hypoglycemic efficacy,as it improves insulin resistance,inhibits oxidative stress and inflammatory response,and down-regulates estrogen level.It is often directly used,modified before use,combined with other formulae(Liuwei Dihuangtang,Shashen Maidongtang,Shenqi Sanjingtang,Huangqi Guizhi Wuwutang,Zengyetang,Zengye Baihutang,etc.),or used together with western medicine(insulin,metformin,pioglitazone,glurenorm,etc.).Modified Yunüjian can be applied for the treatment of type 2 diabetes mellitus,gestational diabetes,polycystic ovary syndrome with insulin resistance,pruritus induced by diabetes mellitus,diabetic peripheral neuropathy,diabetic nephropathy,diabetic ketoacidosis,diabetic retinopathy,and diabetic periodontitis.According to previous experiment,the protection for pancreatic islet β-cells is an important way of Yunüjian to improve diabetes mellitus.The formula can remove damaged proteins and organelles by increasing the expression of autophagy-related 2B(Atg2B),ubiquitin-like-conjugating enzyme(Atg3),γ-aminobutyric acid type A receptor-associated protein(GABARAP),selective autophagy receptor(p62/SQSTM1),etc.Moreover,it plays an active role in islet cell proliferation and apoptosis by regulating the expression of mammalian target of rapamycin(mTOR) and reducing the expression of islet β-cell autophagy gene(Beclin).These are pivotal for maintaining the quantitative structure and functions of islet cells.The modulatory effect of Yunüjian on growth hormone-releasing peptide(ghrelin),gastrin,and growth hormone secretagogue receptor(GHSR) mRNA expression is also the underlying mechanism for the formula to protect pancreatic β-cells.In this study,we summarized the clinical and experimental studies on the therapeutic effect of this formula on diabetes mellitus,discussed the mechanisms,and proposed suggestions on the problems,hoping to provide a reference for the clinical application and further development of Yunüjian.This study is of practical significance for the scientific interpretation of the modern connotation of Yunüjian and the expansion of its clinical application.