中药治疗糖尿病心血管疾病研究进展

Treatment of Cardiovascular Diseases in Diabetes Mellitus with Traditional Chinese Medicine： A Review

摘要:

糖尿病（DM）和心血管疾病（CVD）之间复杂的病理生理机制至今尚未完全阐明，使得其成为人类临床上要面临的巨大挑战之一。目前临床将胰高血糖素样肽-1受体激动剂（GLP1-RA）和钠-葡萄糖共转运体-2抑制剂（SGLT2）用于降低糖尿病患者的心血管风险。中药多成分、多靶点的特点使其具有多样生物活性，在治疗慢性复杂疾病方面发挥独特优势。该综述结合近年来的文献报道，从高血糖、胰岛素抵抗、炎症等糖尿病和心血管疾病的共有危险因素，血清载脂蛋白C3（APOC3）、钙卫蛋白（S100A8/A9）、生长分化因子-15（ GDF-15）、核苷酸结合寡聚化结构域样受体3（NLRP3）APOC3、S100A8/A9、GDF-15、NLRP3等相关靶点和晚期糖基化终末产物、胰岛素抵抗、内皮功能障碍及内质网应激、线粒体功能障碍、肠道菌群紊乱等致病过程进行阐述。此外，总结了现有单体活性成分（如黄芩素、葛根素、姜黄素、三七皂苷、丹参酮Ⅱ_A）、中药（如黄芪、人参、苦参、肉桂、山茱萸）、中药复方（如补脏通络方、益气养阴活血方、参芪复方、黄芪散、当归补血汤、六味地黄丸等）对该疾病的治疗进展。中药主要从抗炎、抗氧化应激、改善血脂异常和胰岛素抵抗、保护胰岛β细胞功能、保护内皮损伤，抑制平滑肌细胞增殖、泡沫细胞形成、巨噬细胞极化、心肌肥大和纤维化、改善肠道菌群紊乱等多方面治疗糖尿病心血管疾病，且涉及胰岛素受体底物/磷脂酰肌醇3-激酶/蛋白激酶B（IRS/PI3K/Akt）、过氧化物酶增殖物激活受体α/γ（PPARα/γ）、核转录因子-κB（NF-κB）、5’-磷酸腺苷活化蛋白激酶（AMPK）、缺氧诱导因子-1-促凋亡蛋白（HIF-1-BNIP）、血管内皮生长因子/缺氧诱导因子-1α（VEGF/HIF-1α）等多条信号通路。以期为中药治疗糖尿病相关心血管疾病提供理论基础和参考依据。

Abstract:

The complex pathophysiological mechanisms between diabetes mellitus and cardiovascular diseases have not yet been fully elucidated， becoming one of the challenges in clinical care. Glucagon-like peptide-1 receptor agonist （GLP1-RA） and sodium glucose cotransporter-2 inhibitors （SGLT2） are clinically used to reduce the cardiovascular risk of patients with diabetes mellitus. Traditional Chinese medicine has diverse biological activities and unique advantages in the treatment of chronic complex diseases due to its multi-component and multi-target effects. Based on recent reports， this paper reviewed the common risk factors of diabetes mellitus and cardiovascular diseases （e.g.， hyperglycemia， insulin resistance， and inflammation）， related targets such as apolipoprotein C-Ⅲ （APOC3）， S100 calcium-binding protein A8/A9 （S100A8/A9）， growth/differentiation factor-15 （GDF-15）， and NACHT， LRR， and PYD domains-containing protein 3 （NLRP3）， advanced glycation end products， insulin resistance， endothelial dysfunction， endoplasmic reticulum stress， mitochondrial dysfunction， and intestinal flora disorder. In addition， this paper summarized the research progress in the treatment of cardiovascular diseases in diabetes mellitus with the active ingredients （e.g.， baicalein， puerarin， curcumin， notoginsenoside， and tanshinone Ⅱ_A）， single herbal medicines （e.g.， Astragali Radix， Ginseng Radix et Rhizoma， Sophorae Flavescentis Radix， Cinnamomi Cortex， and Corni Fructus）， and compound formulas （e.g.， Buzang Tongluo Fang， Yiqi Yangyin Huoxue Fang， Shenqi Fang， Huangqisan， Danggui Buxue Tang， and Liuwei Dihuang Wan） of traditional Chinese medicine. Traditional Chinese medicine mainly treats cardiovascular diseases in diabetes mellitus by reducing inflammation and oxidative stress， ameliorating dyslipidemia and insulin resistance， protecting islet β cell function， repairing endothelial damage， inhibiting smooth muscle cell proliferation， foam cell formation， macrophage polarization， and cardiac hypertrophy and fibrosis， and regulating intestinal flora disorder. These processes involve insulin receptor substrate/ phosphatidylinositol 3-kinase/protein kinase B （IRS/PI3K/Akt）， peroxisome proliferator-activated receptor α/γ （PPAR α/γ）， nuclear factor-kappa B （NF-κB）， adenosine 5′-monophosphate （AMP）-activated protein kinase （AMPK）， hypoxia-inducible factor-1-BCH domain-containing protein （HIF-1-BNIP）， vascular endothelial growth factor/hypoxia-inducible factor-1α （VEGF/HIF-1α） and other signaling pathways. This review is expected to provide a theoretical basis and reference for the treatment of cardiovascular diseases in diabetes mellitus with traditional Chinese medicine.