熊果酸改善胰岛素抵抗的机制研究进展
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摘要
胰岛素抵抗是因各种因素促使胰岛素对葡萄糖摄取与利用效率下降,机体代偿性分泌过多胰岛素而产生高胰岛素血症,以维持血糖稳定的一种病理表现。熊果酸是一种存在于天然植物中的五环三萜类化合物,具有镇静、抗炎、抗菌、抗糖尿病、抗溃疡、降低血糖等多种生物学效应,熊果酸还具有明显的抗氧化功能,因而被广泛的应用于临床治疗中。现有研究证实,熊果酸在胰岛素抵抗机制中具有一定作用,能够调节脂代谢,增加胰岛素敏感性,成为治疗胰岛素抵抗的新型手段。本文就胰岛素抵抗发生机制及熊果酸药理机制展开分析,为熊果酸在临床中治疗胰岛素抵抗提供理论依据。
Insulin resistance is a pathological manifestation of hyperinsulinemia caused by various factors that lead to the decrease of glucose uptake and utilization efficiency and compensatory excessive insulin secretion.The ursolic acid is a pentacyclic triterpenoid found in natural plants. Ursolic acid has many biological effects,such as sedation,anti-inflammatory,antibacterial,anti-diabetic,anti-ulcer,reducing blood sugar and so on.Ursolic acid also has obvious antioxidant function,so it is widely used in clinical treatment.Existing studies have confirmed that ursolic acid has a certain role in the mechanism of insulin resistance,which can regulate lipid metabolism,increase insulin sensitivity,and become an new way to treat insulin resistance.This article analyzes the pathogenesis of insulin resistance and the pharmacological mechanism of ursolic acid in order to provide theoretical bases for ursolic acid in the clinical treatment of insulin resistance.
Insulin resistance is a pathological manifestation of hyperinsulinemia caused by various factors that lead to the decrease of glucose uptake and utilization efficiency and compensatory excessive insulin secretion.The ursolic acid is a pentacyclic triterpenoid found in natural plants. Ursolic acid has many biological effects,such as sedation,anti-inflammatory,antibacterial,anti-diabetic,anti-ulcer,reducing blood sugar and so on.Ursolic acid also has obvious antioxidant function,so it is widely used in clinical treatment.Existing studies have confirmed that ursolic acid has a certain role in the mechanism of insulin resistance,which can regulate lipid metabolism,increase insulin sensitivity,and become an new way to treat insulin resistance.This article analyzes the pathogenesis of insulin resistance and the pharmacological mechanism of ursolic acid in order to provide theoretical bases for ursolic acid in the clinical treatment of insulin resistance.
引文
1 王海鹏,孟庆跃.2000-2009年我国成年人诊断糖尿病流行趋势分析.中国预防医学杂志,2013,14:132-135.
2 Castro AJ,Frederico MJ,Cazarolli LH,et al.The mechanism of action of ursolic acid as insulin secretagogue and insulinomimetic is mediated by cross-talk between calcium and kinases to regulate glucose balance.BBA,2015,1850:51-61.
3 陈涛,王中心,黄丽华,等.初诊2型糖尿病合并高血压患者血清脂联素和改良稳态模型评估法计算的胰岛素抵抗指数的变化及相关性.中华高血压杂志,2015,23:452-456.
4 张新华,何文华,朱萱,等.熊果酸对活化型肝星状细胞NADPH氧化酶亚基p47～(Phox)表达及ERK1/2信号通路活化的影响.第二军医大学学报,2012,33:590-594.
5 曾璐,唐外姣,殷锦锦,等.熊果酸改善肝细胞脂肪变性的实验研究.中药材,2015,38:1049-1052.
6 周淑娴,雷娟,张玉玲,等.高血压患者胰岛素抵抗与血清脂联素及炎症标志物水平.中华高血压杂志,2008,16:166-170.
7 李淑梅,钟世顺.胰岛素抵抗与高血压及抗高血压药物的关系.国外医学.心血管疾病分册,2000,27:15-18.
8 周咏梅,舒燕.原发性高血压合并非糖尿病患者血浆肿瘤坏死因子-α水平变化与胰岛素抵抗的关系.实用医院临床杂志,2018,15:76-78.
9 张燕,王广,刘佳,徐援.H型高血压与胰岛素抵抗的关系研究.中国全科医学,2016,19:2271-2274、2283.
10 杨永青,杨明庆.肥胖诱发胰岛素抵抗的炎性机制.中国生物化学与分子生物学报,2012,28:692-699.
11 王正义,甘霖莉,左之才.抵抗素诱导肥胖机体胰岛素抵抗的炎症机制.动物营养学报,2016,28:1670-1676.
12 刘颐轩,宋桉,王芸,等.氧化应激在肥胖及胰岛素抵抗中的作用研究进展.解放军医药杂志,2014,26:99-101.
13 张青,刘雅娟,徐璐,等.脂联素对胰岛素抵抗及心室重构的影响研究.中国全科医学,2016,19:1401-1407.
14 陈海英.脂联素瘦素及胰岛素抵抗与非酒精性脂肪肝的关系.河北医学,2013,19:510-513.
15 汪学军,姜志胜,黄佳克.2型糖尿病合并肥胖患者脂联素水平与胰岛素抵抗的相关性.中国动脉硬化杂志,2009,17:535-538.
16 洪洁,顾卫琼,张翼飞,等.胰岛素抵抗综合征患者血清脂联素和胰岛素敏感性的相关性研究.中华内分泌代谢杂志,2003,19:19-22.
17 陈珍珍,曹振强,周广宇,等.东北汉族人群抵抗素基因rs1862513(G/C)多态性与2型糖尿病相关性研究.中国实验诊断学,2017,21:1185-1188.
18 周爱芬,李真真,王静,等.Chemerin、脂联素、抵抗素及Hcy在GDM患者中的水平变化及其意义.实验与检验医学,2019,37:104-106.
19 祖米拉提·塔西买买提,才层,张仑.PCOS患者血清TNF-α、IGF-1、瘦素、sOB-R、脂联素的变化及与患者发生胰岛素抵抗的关系.中国妇幼保健,2018,33:5772-5774.
20 牟晓华,王家琳.肥胖型2型糖尿病胰岛素抵抗机制及治疗研究.中医药临床杂志,2015,27:1063-1066.
21 许乐,逄晓阳,芦晶,等.HepG2细胞胰岛素抵抗模型的建立及其应用.核农学报,2017,31:1775-1781.
22 雷达,李永利,祁军安.熊果酸对HepG2增殖和凋亡的影响及部分机制研究.中国现代普通外科进展,2017,20:259-263.
23 王冠梁,刘甲寒,李迪,等.熊果酸通过PPARα/γ改善HepG2细胞胰岛素抵抗模型糖代谢的机制.中药药理与临床,2012,28:24-29.
24 Zhang W,Hong D,Zhou Y,et al.Ursolic acid and its derivative inhibit protein tyrosine phosphatase 1B,enhancing insulin receptor phosphorylation and stimulating glucose uptake.BBA,2006,1760:1505-1512.
25 王琳,王冠梁,刘甲寒,等.熊果酸通过过氧化物酶增殖受体α和γ信号通路改善KKAy小鼠肝脏胰岛素抵抗的机制.中西医结合学报,2012,10:793-799.
26 Lu Yang,Xiaozhuo Liu,Zengbing Lu,et al.Ursolic acid induces doxorubicin-resistant HepG2 cell death via the release of apoptosis-inducing factor.Cancer Letters,2010,298:128-138.
27 Jun Lu,Dong-mei Wu,Yuan-lin Zheng,et al.Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IκB kinase β/nuclear factor-κB-mediated inflammatory pathways in mice.Brain Behavior and Immunity,2011,25:1658-1667.
28 张杰,吴淑艳,王琳,等.熊果酸对胰岛素抵抗大鼠肝脏组织PTP-1B、IRS-2mRNA表达的影响.江苏中医药,2010,42:69-71.
29 王冠梁,李迪,王琳,等.熊果酸通过葡萄糖转运体改善KKAy小鼠胰岛素抵抗的机制.中华中医药杂志,2013,28:787-790.
30 曾光,陈芳,邵峰,等.熊果酸对大鼠CIA模型关节TNF-α、IL-17、PGE2表达的影响.湖南中医药大学学报,2018,38:13-16.
31 陈振宙,张雪丹.熊果酸对四氯化碳所致大鼠肝纤维化及门静脉高压的影响.安徽医药,2017,21:635-639.
2 Castro AJ,Frederico MJ,Cazarolli LH,et al.The mechanism of action of ursolic acid as insulin secretagogue and insulinomimetic is mediated by cross-talk between calcium and kinases to regulate glucose balance.BBA,2015,1850:51-61.
3 陈涛,王中心,黄丽华,等.初诊2型糖尿病合并高血压患者血清脂联素和改良稳态模型评估法计算的胰岛素抵抗指数的变化及相关性.中华高血压杂志,2015,23:452-456.
4 张新华,何文华,朱萱,等.熊果酸对活化型肝星状细胞NADPH氧化酶亚基p47～(Phox)表达及ERK1/2信号通路活化的影响.第二军医大学学报,2012,33:590-594.
5 曾璐,唐外姣,殷锦锦,等.熊果酸改善肝细胞脂肪变性的实验研究.中药材,2015,38:1049-1052.
6 周淑娴,雷娟,张玉玲,等.高血压患者胰岛素抵抗与血清脂联素及炎症标志物水平.中华高血压杂志,2008,16:166-170.
7 李淑梅,钟世顺.胰岛素抵抗与高血压及抗高血压药物的关系.国外医学.心血管疾病分册,2000,27:15-18.
8 周咏梅,舒燕.原发性高血压合并非糖尿病患者血浆肿瘤坏死因子-α水平变化与胰岛素抵抗的关系.实用医院临床杂志,2018,15:76-78.
9 张燕,王广,刘佳,徐援.H型高血压与胰岛素抵抗的关系研究.中国全科医学,2016,19:2271-2274、2283.
10 杨永青,杨明庆.肥胖诱发胰岛素抵抗的炎性机制.中国生物化学与分子生物学报,2012,28:692-699.
11 王正义,甘霖莉,左之才.抵抗素诱导肥胖机体胰岛素抵抗的炎症机制.动物营养学报,2016,28:1670-1676.
12 刘颐轩,宋桉,王芸,等.氧化应激在肥胖及胰岛素抵抗中的作用研究进展.解放军医药杂志,2014,26:99-101.
13 张青,刘雅娟,徐璐,等.脂联素对胰岛素抵抗及心室重构的影响研究.中国全科医学,2016,19:1401-1407.
14 陈海英.脂联素瘦素及胰岛素抵抗与非酒精性脂肪肝的关系.河北医学,2013,19:510-513.
15 汪学军,姜志胜,黄佳克.2型糖尿病合并肥胖患者脂联素水平与胰岛素抵抗的相关性.中国动脉硬化杂志,2009,17:535-538.
16 洪洁,顾卫琼,张翼飞,等.胰岛素抵抗综合征患者血清脂联素和胰岛素敏感性的相关性研究.中华内分泌代谢杂志,2003,19:19-22.
17 陈珍珍,曹振强,周广宇,等.东北汉族人群抵抗素基因rs1862513(G/C)多态性与2型糖尿病相关性研究.中国实验诊断学,2017,21:1185-1188.
18 周爱芬,李真真,王静,等.Chemerin、脂联素、抵抗素及Hcy在GDM患者中的水平变化及其意义.实验与检验医学,2019,37:104-106.
19 祖米拉提·塔西买买提,才层,张仑.PCOS患者血清TNF-α、IGF-1、瘦素、sOB-R、脂联素的变化及与患者发生胰岛素抵抗的关系.中国妇幼保健,2018,33:5772-5774.
20 牟晓华,王家琳.肥胖型2型糖尿病胰岛素抵抗机制及治疗研究.中医药临床杂志,2015,27:1063-1066.
21 许乐,逄晓阳,芦晶,等.HepG2细胞胰岛素抵抗模型的建立及其应用.核农学报,2017,31:1775-1781.
22 雷达,李永利,祁军安.熊果酸对HepG2增殖和凋亡的影响及部分机制研究.中国现代普通外科进展,2017,20:259-263.
23 王冠梁,刘甲寒,李迪,等.熊果酸通过PPARα/γ改善HepG2细胞胰岛素抵抗模型糖代谢的机制.中药药理与临床,2012,28:24-29.
24 Zhang W,Hong D,Zhou Y,et al.Ursolic acid and its derivative inhibit protein tyrosine phosphatase 1B,enhancing insulin receptor phosphorylation and stimulating glucose uptake.BBA,2006,1760:1505-1512.
25 王琳,王冠梁,刘甲寒,等.熊果酸通过过氧化物酶增殖受体α和γ信号通路改善KKAy小鼠肝脏胰岛素抵抗的机制.中西医结合学报,2012,10:793-799.
26 Lu Yang,Xiaozhuo Liu,Zengbing Lu,et al.Ursolic acid induces doxorubicin-resistant HepG2 cell death via the release of apoptosis-inducing factor.Cancer Letters,2010,298:128-138.
27 Jun Lu,Dong-mei Wu,Yuan-lin Zheng,et al.Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IκB kinase β/nuclear factor-κB-mediated inflammatory pathways in mice.Brain Behavior and Immunity,2011,25:1658-1667.
28 张杰,吴淑艳,王琳,等.熊果酸对胰岛素抵抗大鼠肝脏组织PTP-1B、IRS-2mRNA表达的影响.江苏中医药,2010,42:69-71.
29 王冠梁,李迪,王琳,等.熊果酸通过葡萄糖转运体改善KKAy小鼠胰岛素抵抗的机制.中华中医药杂志,2013,28:787-790.
30 曾光,陈芳,邵峰,等.熊果酸对大鼠CIA模型关节TNF-α、IL-17、PGE2表达的影响.湖南中医药大学学报,2018,38:13-16.
31 陈振宙,张雪丹.熊果酸对四氯化碳所致大鼠肝纤维化及门静脉高压的影响.安徽医药,2017,21:635-639.