[1]刘 清,王 芳,张淑娟,等.白虎加人参汤对2型糖尿病大鼠抗氧化应激作用及机制研究[J].陕西中医,2024,(9):1166-1171.[doi:DOI:10.3969/j.issn.1000-7369.2024.09.003]
 LIU Qing,WANG Fang,ZHANG Shujuan,et al.Effect and mechanism of Baihu jia Renshen decoction on anti-oxidative stress in type 2 diabetic rats[J].,2024,(9):1166-1171.[doi:DOI:10.3969/j.issn.1000-7369.2024.09.003]
点击复制

白虎加人参汤对2型糖尿病大鼠抗氧化应激作用及机制研究
分享到:

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2024年9期
页码:
1166-1171
栏目:
基础研究
出版日期:
2024-09-05

文章信息/Info

Title:
Effect and mechanism of Baihu jia Renshen decoction on anti-oxidative stress in type 2 diabetic rats
作者:
刘 清1王 芳2 张淑娟2 RASIKA Gunarathne3严军虎4
(1.陕西中医药大学,陕西 咸阳 712046; 2.陕西能源职业技术学院, 陕西 咸阳 712000; 3.Auckland Bioengineering Institute,University of Auckland,Private Bag 92019,Auckland 1142,New Zealand; 4.陕西师范大学医院,陕西 西安 710062)
Author(s):
LIU QingWANG FangZHANG ShujuanRASIKA GunarathneYAN Junhu
(Shaanxi University of Chinese Medicine,Xianyang 712046,China)
关键词:
2型糖尿病 白虎加人参汤 抗氧化应激 胰岛素抵抗 胰岛β细胞
Keywords:
Type 2 diabetic Baihu jia Renshen decoction Antioxidant stress Insulin resistance Islet β cells
分类号:
R 587.1
DOI:
DOI:10.3969/j.issn.1000-7369.2024.09.003
文献标志码:
A
摘要:
目的:研究白虎加人参汤(BHJRS)对2型糖尿病(T2DM)模型大鼠抗氧化应激的作用,并初步探讨其作用机制。方法:随机取8只SD大鼠作为对照组(NC组),其余SD大鼠采用高脂高糖联合低剂量腹腔注射STZ(45 mg/kg)制备T2DM大鼠模型。将成模大鼠随机分为模型(DM)组、阳性药[盐酸二甲双胍(Met),200 mg/kg]组、BHJRS 高剂量组(BHJRS-H,BHJRS溶液37.8 g/kg)、BHJRS低剂量组(BHJRS-L,BHJRS溶液18.9 g/kg),连续给药8周。测定各组大鼠第0、2、4、6、8周空腹血糖(FBG),检测糖化血红蛋白(HbAlc)、胰岛素(INS)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)水平并计算ISI值,观察胰腺组织病理学形态变化; 检测胰腺组织中B淋巴细胞瘤-2基因(Bcl-2)、胱天蛋白酶3(Caspase-3)、Bcl-2相关X蛋白(Bax)的mRNA和蛋白水平; 检测胰腺组织中蛋白激酶B(AKT)/糖原合成激酶-3β(GSK-3β)/核因子NF-E2相关因子(Nrf2)信号通路关键蛋白的表达。结果:与DM组比较,Met 组、BHJRS-H组和BHJRS-L组显著降低T2DM大鼠FBG、血清中HbAlc、MDA水平(P<0.05),显著升高血清中INS、CAT、SOD、GSH-Px水平和 ISI值(P<0.05); 显著上调胰腺组织中p-AKT/AKT、p-GSK-3β/GSK-3β、n-Nrf2、血红素加氧酶-1(HO-1)水平(P<0.05),显著下调Bax/Bcl-2、Caspase-3、n-Fyn水平(P<0.05),胰腺组织病理变化均不同程度改善。结论:BHJRS对胰腺组织有一定的抗氧化应激作用,其原因可能在于调节AKT/GSK-3β/Nrf2信号通路中相关蛋白的表达有关。
Abstract:
Objective:To study the effect and mechanism of Baihu jia Renshen decoction(BHJRS)on oxidative stress in Type 2 diabetic rats,and to explore its mechanism.Methods:Eight SD rats were randomly selected as the control group(NC group),and the remaining SD rats were treated with high fat and high sugar combined with low dose of STZ(45 mg/kg)intraperitoneally to create T2DM rat model.The model rats were randomly divided into a model(DM)group,a positive drug [metformin(Met),200 mg/kg group],a BHJRS high-dose group(BHJRS-H,37.8 g/kg),a BHJRS low-dose group(BHJRS-L,18.9 g/kg).The drug was administered continuously for 8 weeks.FBG was measured at the 0,2,4,6 and 8 weeks in each group,and the levels of HbAlc,INS,MDA,GSH-Px,SOD and CAT were detected,and ISI values were calculated.The morphological changes of pancreatic histopathology were observed.The mRNA and protein levels of Bcl-2,Bax and Caspase-3 were detected in pancreatic tissue.The expression of AKT/GSK-3β/Nrf2 signaling pathway in pancreatic tissue was detected.Results:Compared with DM group,the levels of FBG,serum HbAlc and MDA in Met group,BHJRS-H group and BHJRS-L group were significantly decreased(P<0.05),and the levels of INS,CAT,SOD,GSH-Px and ISI in serum were significantly increased(P<0.05).Significantly increased the p-Akt /AKT ratio,p-GSK-3β/GSK-3β ratio,n-Nrf2 and heme oxygenase-1(HO-1)levels in pancreatic tissue(P<0.05),and significantly decreased the Bax/Bcl-2 ratio,Caspase-3 and n-Fyn levels(P<0.05).The histopathologic changes of pancreas were improved in different degree.Conclusion:BHJRS has a certain effect on the anti-oxidative stress of pancreatic tissue,and its mechanism may be related to the regulation of the expression of related proteins in the AKT/GSK-3β/Nrf2 signaling pathway.

参考文献/References:

[1] 陶乐维.不同剂量六味地黄丸对胰岛素抵抗小鼠糖代谢及体重的影响[J].陕西中医,2022,43(3):275-278.
[2] CAI L,LI W,WANG G W,et al.Hyperglycemia induced apoptosis in mouse myocardium:Mitochondrial cytochrome C-mediated caspase-3 activation pathway[J].Diabetes,2002,51:1938-1948.
[3] NGUYEN T,NIOI P,PICKETT C B.The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress[J].J Biol Chem,2009,284(20):13291-13295.
[4] ENGELMAN J A,LUO J,CANTLEY L C.The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism[J].Nat Rev Genet,2006,7(8):606-619.
[5] MIN K J,LEE J T,JOE E H,et al.An IkappaBalpha phosphorylation inhibitor induces heme oxygenase-1(HO-1)expression through the activation of reactive oxygen species(ROS)-Nrf2-ARE signaling and ROS-PI3K/Akt signaling in an NF-kappaB-independent mechanism[J].Cell Signal,2011,23(9):1505-1513.
[6] LI L,DONG H,SONG E,et al.Nrf2/ARE pathway activation,HO-1 and NQO1 induction by polychlorinated biphenyl quinone is associated with reactive oxygen species and PI3K/AKT signaling[J].Chem Biol Interact,2014,209:56-67.
[7] 季学清,刘萍,陈宝瑾,等.冠心康方加减联合西药治疗冠心病合并2型糖尿病气虚痰瘀证疗效研究[J].陕西中医,2020,41(9):1208-1211.
[8] 姬荣伟,刘秋霞,田亚宁,等,卵巢术前新辅助化疗疗效及对组织CA-125、CD146、SP70的表达影响[J].陕西医学杂志,2018,47(12):1648-1650,1666.
[9] 曹亮,田皎丁,杨娜,等.针刺联合大黄虫汤加味治疗糖尿病周围神经病变临床研究[J].陕西中医,2021,42(8):1120-1123.
[10] 唐智.经方治疗2型糖尿病的Meta分析和系统评价[D].南京:南京中医药大学,2020.
[11] 向琴,蒋宛瑾,喻嵘,等.白虎加人参汤对2型糖尿病小鼠肠道UCP2、AMPK表达及GLP-1分泌的影响[J].湖南中医药大学学报,2020,40(12):1444-1448.
[12] 杨金伟,马志辉,赵灿,等.白虎加人参汤含药血浆对高糖环境下SD大鼠胰岛细胞增殖、凋亡及氧化应激水平的影响[J].中医杂志,2019,60(12):1951-1956.
[13] 姜维娜,马尧.白虎加人参汤加减联合西药治疗对气阴两虚型糖尿病患者生命质量与心理健康的影响[J].世界中医药,2018,13(2):374-377.
[14] 许慧英.白虎加人参汤联合降糖西药治疗2型糖尿病临床疗效的系统评价[D].大连:大连医科大学,2016.
[15] 武翠凡,辛建勋.白虎加人参汤联合西药治疗2型糖尿病51例[J].中国社区医师,2006,22(3):37.
[16] 陈益山.白虎加人参汤治疗初发2型糖尿病的疗效观察[J].深圳中西医结合杂志,2014,24(5):142-144.
[17] 冯海霞.白虎加人参汤治疗气阴两虚、燥热偏盛型初发2型糖尿病疗效观察[D].济南:山东中医药大学,2009.
[18] 游龙,白会玲,谷艳丽.白虎人参汤联合降糖药治疗2型糖尿病疗效观察[J].现代中西医结合杂志,2009,18(19):2286-2287.
[19] 王芳,姚敏娜,张雅,等.基于PI3K/Akt/FoxO1信号通路探索白虎加人参汤对2型糖尿病大鼠胰腺组织的保护作用[J].中成药,2022,44(10):3315-3320.
[20] 王帮众.益气养阴化痰祛瘀方对2型糖尿病大鼠胰岛β细胞的保护作用及机制[D].北京:北京中医药大学,2015.
[21] WEI W,LIU Q,TAN Y,et al.Oxidative stress,diabetes,and diabetic complications[J].Hemoglobin,2009,33(5):370-377.
[22] ZHANG F,YE C,LI G,et al.The rat model of type 2 diabetic mellitus and its glycometabolism characters[J].Exp Anim,2003,52(5):401-407.
[23] MINN A H,HAFELE C,ShALEV A.Thioredoxin-interacting protein is stimulated by glucose through a carbohydrate response element and induces beta-cell apoptosis[J].Endocrinology,2005,146(5):2397-2405.
[24] KIM H J,VAZIRI N D.Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure[J].American Journal of Physiology-renal Physiology,2010,298(3):662-671.
[25] JAIN A K,JAISWAL A K.GSK-3 beta acts upstream of Fyn kinase in regulation of nuclear export and degradation of NF-E2 related factor 2[J].J Biol Chem,2007,282(22):16502-16510.

相似文献/References:

[1]李向辉,卢文杰.葛黄降糖汤治疗2型糖尿病合并颈动脉硬化临床研究*[J].陕西中医,2019,(5):580.
 LI Xianghui,LU Wenjie..Effect of Gehuang Jiangtang decoction on mellitus complicated with carotid arteriosclerosis in type 2 diabetes patients[J].,2019,(9):580.
[2]杨斯皓,马方霞,詹 云.一贯煎合六味地黄汤配合西药治疗2型糖尿病合并非酒精性脂肪肝临床疗效及对患者生活质量的评价*[J].陕西中医,2019,(8):1006.
 YANG Sihao,MA Fangxia,ZHAN Yun..Clinical efficacy and quality of life evaluation of Yiguanjian plus Liuwei Dihuang decoction with western medicine in the treatment of type 2 diabetes with nonalcoholic fatty liver disease[J].,2019,(9):1006.
[3]孙晓红,陈学彬△.芪精丹兰汤对伴有左心室舒张功能不全的2型糖尿病合并代谢综合征患者糖脂代谢、心率变异性的影响*[J].陕西中医,2019,(10):1336.
 SUN Xiaohong,CHEN Xuebin..Effect of Qijing Danlan decoction on glucose and lipid metabolism and heart rate variability in patients with type 2 diabetes mellitus complicated with MS with left ventricular diastolic dysfunction[J].,2019,(9):1336.
[4]訾 璐,胡小军△,王 玉,等.针刺中脘穴联合自拟茶方对2型糖尿病患者血糖水平的影响*[J].陕西中医,2019,(10):1460.
 ZI Lu,HU Xiaojun,WANG Yu,et al.Effect of zhong wan acupuncture combined with selfdesigned tea prescription on blood glucose level in patients with type 2 diabetes mellitus[J].,2019,(9):1460.
[5]文启友,周 伶,马若梦,等.化瘀利尿法论治2型糖尿病探析[J].陕西中医,2021,(6):761.[doi:DOI:10.3969/j.issn.1000-7369.2020.06.021]
[6]谢兆桃,周卓宁,郑 鹏,等.从中焦论治2型糖尿病患者餐后血糖波动[J].陕西中医,2021,(6):764.[doi:DOI:10.3969/j.issn.1000-7369.2020.06.022]
[7]胡全穗,伍宗明.运用中药药对配伍优化消渴病中医防治方案临床研究[J].陕西中医,2021,(8):1084.[doi:DOI:10.3969/j.issn.1000-7369.2020.08.024]
 HU Quansui,WU Zongming.Clinical research on optimizing the TCM prevention and treatment of Xiaoke by using compatibility of herb-partners[J].,2021,(9):1084.[doi:DOI:10.3969/j.issn.1000-7369.2020.08.024]
[8]卢 昉,刘晓霞,梁佩玲,等.清热益气降糖方对2型糖尿病患者胰岛α、β细胞功能的影响[J].陕西中医,2021,(10):1400.[doi:DOI:10.3969/j.issn.1000-7369.2020.10.019]
[9]刘厚利,呼兴华,何 莉,等.基于数据挖掘许建秦治疗湿热内蕴型糖尿病用药规律分析[J].陕西中医,2021,(10):1455.[doi:DOI:10.3969/j.issn.1000-7369.2020.10.035]
[10]陈继玲,任珍珍,王劭敏,等.玉泉丸合生脉散联合二甲双胍治疗气阴两虚证2型糖尿病临床研究[J].陕西中医,2021,(11):1553.[doi:DOI:10.3969/j.issn.1000-7369.2020.11.013]
 CHEN Jiling,REN Zhenzhen,WANG Shaomin,et al.Efficacy of Yuquan pills with Shengmai powder and metformin tablets in the treatment of T2DM with deficiency of Qi and Yin[J].,2021,(9):1553.[doi:DOI:10.3969/j.issn.1000-7369.2020.11.013]
[11]陈泽瑶,陈家祈,张 琦,等.白虎加人参汤治疗2型糖尿病Meta分析[J].陕西中医,2024,(7):989.[doi:DOI:10.3969/j.issn.1000-7369.2024.07.029]

备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(82374077); 陕西省自然科学基础研究计划项目(2021IQ-888); 陕西省教育厅科研计划项目(21JK0578)
更新日期/Last Update: 2024-09-09