[1]乔 进,窦志华,吴 锋,等.灵芝多糖联合二甲双胍预防糖尿病大鼠主动脉病变及对VEGF表达的影响[J].中国药理学通报,2014,(08):1079.
 QIAO Jin,DOU Zhi-hua,WU Feng,et al.Effect of combination of ganoderma lucidum polysaccharide and metformin on aortic lesions and expression of VEGF in type 2 diabetic rats[J].Chinese Pharmacological Bulletin,2014,(08):1079.
点击复制

灵芝多糖联合二甲双胍预防糖尿病大鼠主动脉病变及对VEGF表达的影响()
分享到:

《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2014年08期
页码:
1079
栏目:
论著
出版日期:
2014-08-15

文章信息/Info

Title:
Effect of combination of ganoderma lucidum polysaccharide and metformin on aortic lesions and expression of VEGF in type 2 diabetic rats
作者:
乔 进1窦志华1吴 锋2孟国梁2陈 惠3郑惠华3
南通市第三人民医院1.药剂科、
2.药理学系,江苏 南通 226001;
3.江苏安惠生物科技有限公司,江苏 南通 226006
Author(s):
QIAO JinDOU Zhi-huaWU FengMENG Guo-liangCHEN HuiZHEN Hui-hua
1. Dept of Pharmacy,the Third People's Hospital of Nantong, Nantong Jiangsu 226001,China;
2. Dept of Pharmacology,Medical College,Nantong University,Nantong Jiangsu 226001,China;
3. Jiangsu Anhui Biological Technology Co. Ltd,Nantong Jiangsu 226006,China
关键词:
灵芝多糖 二甲双胍 糖尿病大鼠 胸主动脉 氧化应激 血管内皮生长因子
Keywords:
ganoderma lucidum polyccharide metformin diabetes mellitus rats thoracic aorta oxidative stress VEGF
分类号:
R-332;R284.1;R322.121;R587.1;R977.15
文献标志码:
A
摘要:
目的 探讨灵芝多糖联合二甲双胍对2型糖尿病大鼠胸主动脉病变的预防作用及其作用机制。方法 SD大鼠高能量饮食4周后,腹腔注射小剂量链脲佐菌素(STZ)30 mg·kg-1建立2型糖尿病(type 2 diabetes mellitus,T2DM)大鼠模型。成模后随机分为模型组、灵芝多糖组(灵芝多糖600 mg·kg-1)、二甲双胍组(二甲双胍600 mg·kg-1)及联合用药组(灵芝多糖300 mg·kg-1+二甲双胍300 mg·kg-1),另设正常对照组。给药12周末测定大鼠空腹血糖、血清过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、总胆固醇(TC)、甘油三酯(TG)水平; HE染色观察胸主动脉病理学变化; 免疫组化、蛋白印记法检测胸主动脉VEGF的表达。结果 联合用药组大鼠空腹血糖、血脂水平明显降低,血清CAT、GSH-Px水平明显升高,胸主动脉血管内皮生长因子(VEGF)表达得到抑制,主动脉病理观察显示联合用药组内膜增厚、内皮脂质沉积较模型组少。结论 灵芝多糖联合二甲双胍对2型糖尿病大鼠主动脉病变有预防作用,其机制可能与抑制主动脉氧化应激,调节血脂,下调主动脉VEGF的表达有关。
Abstract:
Aim To investigate the effects and mecha of ganoderma lucidum polysaccharides and metformin on pathological changes of thoracic aorta in diabetic rats and the mechanisms. Methods SD rats were fed with high fat diet for 4 weeks and injected with streptozotocin(30mg·kg-1)to replicate type 2 diabetic model.The diabetic rats were randomly into diabetes group, ganoderma lucidum polysaccharides group(600 mg·kg-1),metformin group(600 mg·kg-1),combination group(ganoderma lucidum polysaccharides 300 mg·kg-1 + metformin 300 mg·kg-1)and normal control group. After 12 weeks' treatment, the levels of fasting serum glucose, the activity of catalase(CAT),glutathione peroxidase(GSH-Px),total cholesterol(TC)and triglyceride(TG)in serum were detected.Pathological changes of thoracic aorta were observed by HE staining.Immunohistochemy and Western blot were used to detect thoracic aorta VEGF protein expression. Results Combination group could lower fasting serum glucose and blood fat significantly, meanwhile the activity of CAT and GSH-Px in serum was improved.The expression of VEGF in thoracic aorta was repressed.The result of HE staining suggested that the lipid deposits in aortic endothelium in combination group were less than those in the model group. Conclusions Ganoderma lucidum polysaccharides combined with metformin has an obvious prevention on pathological changes of thoracic aorta in diabetic rats.The possible mechanism may be related to repressing oxidative stress of thoracic aorta, regulating the dyslipidemia, and the down regulation of the expression of VEGF in thoracic aorta.

参考文献/References:

[1] 王玉珍,赵德明,许樟荣,等.糖尿病合并大血管病变的危险性研究4845例糖尿病患者合并慢性并发症及治疗现状调查[J].中国糖尿病杂志,2006,14(3):197-200. [1] Wang Y Z,Zhao D M,Xu Z R,et al. A survey on the diabetic macrovascular complications and related risk factors in the 4845 Chinese diabetic patients[J].Chin J Diabetes,2006,14(3):197-200.
[2] Huang S Q,Li J W,Li Y Q,Wang Z. Purification and structural characterization of a new water-soluble neutral polysaccharide GLP-F1-1 from Ganoderma lucidum[J].Int J Biol Macromol,2011,48(1):165-9.
[3] Anfossi G,Russo I,Bonomo K,et al.The cardiovascular effects of metformin:further reasons to consider an old drug as a cornerstone in the therapy of type 2 diabetes mellitus[J].Curr Vasc Pharmacol,2010,8(3):327-37.
[4] 吴 锋,孟国梁,徐济良,等.灵芝多糖抑制NADPH氧化酶表达防治大鼠动脉粥样硬化[J].中国药理学通报,2012,28(7):944-7.
[4] Wu F,Meng G L,Xu J L,et al. The anti-atherosclerotic effect of Ganoderma lucidum polysaccharides via down-regulation of vascular NADPH oxidases expression in atherosclerosis rats[J].Chin Pharmacol Bull,2012,28(7):944-7.
[5] 乔 进,薛 华,孟国梁,等.灵芝多糖对2型糖尿病大鼠胸主动脉内皮功能的保护作用[J].中国动脉硬化杂志,2009,17(9):709-13.
[5] Qiao J,Xue H,Meng G L,et al.Protective effects of ganoderma lucidum polysaccharides on aorta pectoralis endothelial in Type2 diebetes rats in vivo[J].Chin J Arterioscler,2009,17(9):709-13.
[6] Lewis A,Steadman R,Manley P,et al.Diabetic nephropathy,inflammation,hyaluronan and interstitial fibrosis[J].Histol Histopathol,2008,23(6):731-9.
[7] Johansen J S,Harris A K,Rychly D J,Erygul A.Oxidatives tress and the use of antioxidants in diabetes:Linking basic science to clinical practice [J].Cardiovasc Diabetol,2005,4(1):5.
[8] Kitajima S,Jin Y,Koike T,et al.Lp(a)enhances coronary atherosclerosis in transgenic Watanabe heritable hyperlipidemic rabbits[J].Atherosclerosis,2007,193(2):269-76.
[9] Matsul T,Yamagishi S,Ueda S,et al.Telmisartan,an angiotensin Ⅱ type 1 receptor blocker,inhibits advanced glycation end-product(AGE)-induced monocyte chemoattractant protein-1 expression in mesangial cells through downregulation of receptor for AGEs via peroxisome proliferator-activated receptor activation[J].J Int Med Res,2007,35(4):482-9.
[10] 李 韬.糖尿病血管内皮损伤机制研究进展[J].中医药临床杂志,2010,22(3):275-7.
[10] Li T.The research progress of vascular endothelial injury mechanism of diabetes[J].Clin J Tradit Chin Med,2010,22(3):275-7.
[11] 常丽萍,张秋燕,韩建科,等.通心络超微粉对缺血性脑卒中大鼠微血管新生影响的实验研究[J].中国药理学通报,2012,28(7):1015-8.
[11] Chang L P,Zhang Q Y,Han J K,et al. Experimental study on the interventional effects of Tongxinluo supermicropowder on angiogenesis of ischemic stroke rats[J].Chin Pharmacol Bull,2012,28(7):1015-8.
[12] 张 力,葛才保,黄中伟.2型糖尿病糖耐量试验中血管内皮细胞生长因子动态观察[J].检验医学,2013,28(7):577-80.
[12] Zhang L,Ge C B,Huang Z W. The dynamic observation of vascular endothelial growth factor in type 2 diabetes mellitus patients during glucose tolerance test[J].Laborat Med,2013,28(7):577-80.
[13] 祁 玥,郑亚宁.血管内皮生长因子的研究进展[J].青海师范大学学报(自然科学版),2010,31(4):61-6.
[13] Qi Y,Zheng Y L.The research progress of vascular endothelial growth factor[J].J Qinghai Normal Univ(Nat Sci Edit),2010,31(4):61-6.
[14] Long J,Wang Y,Wang W,et al.Identification of micro RNA-93 as a novel regulator of vascular endothelial growth factor in hyperglycemic conditions[J].J Biol Chem,2010,285(30):23457-65.
[15] 易茜璐,于明香.糖尿病视网膜病变的发病机制[J].复旦学报(医学版),2010,37(5):604-7.
[15] Yi X L,Yu M X.Pathogenesis of diabetic retinopathy[J].Fudan Univ J Med Sci,2010,37(5):604-7.
[16] 陈 良,蒋锦琪.血管内皮生长因子及其在心血管疾病中的研究进展[J].中国医师进修杂志,2010,33(16):73-5.
[16] Chen L,Jiang J Q.Vascular endothelial growth factor and the research progress in cardiovascular disease[J].Chin J Postgrad Med,2010,33(16):73-5.
[17] 张伟丽,惠汝太.VEGF及其受体在动脉粥样硬化中的作用[J].中国分子心脏病学杂志,2005,5(3):568-73.
[17] Zhang W L,Hui N T.The biological role of VEGF and its receptors in atherosclerosis[J].Mol Cardiol China,2005,5(3):568-73.
[18] Sun K,Wernstedt Asterholm I,Kusminski C M,et al. Dichotomous effects of VEGF-A on adipose tissue dysfunction[J].Proc Natl Acad Sci USA,2012,109(15):5874-9.
[19] Elshal M F,Kumosani T A,Abulnaja K O,et al.Influence of defatted flaxseed diet on insulinsensitivity,vascular permeability and lipid profile in a rat model of type 2 diabetes mellitus[J].J Med Plants Res,2012,6(11):2188-93.

相似文献/References:

[1]李颖博,李宇华,王瑞,等.灵芝多糖对肿瘤细胞与内皮细胞相互作用的影响[J].中国药理学通报,2008,(02):0.
 LI Ying bo,LI Yu hua,WANG Rui,et al.Effect of Ganoderma lucidum polysaccharides(GlPS) on tumorendothelium interactions[J].Chinese Pharmacological Bulletin,2008,(08):0.
[2]耿卫朴,徐曼,罗祎,等.灵芝多糖和当归多糖促进人外周血T淋巴细胞增殖和分泌IFNγ[J].中国药理学通报,2012,(05):655.
 GENG Wei pu,XU Man,LUO Yi,et al.The promotional effect of Ganoderma lucidum polysaccharide and Angelica sinensis polysaccharide on the proliferation and IFNγ secretion of human peripheral blood T lymphocytes[J].Chinese Pharmacological Bulletin,2012,(08):655.
[3]吴锋,孟国梁,常珊珊,等.灵芝多糖抑制NADPH氧化酶表达防治大鼠动脉粥样硬化[J].中国药理学通报,2012,(07):944.
 WU Feng,MENG Guo liang,CHANG Shan shan,et al.The antiatherosclerotic effect of Ganoderma lucidum Polysaccharides via downregulation of vascular NADPH oxidases expression in atherosclerosis rats[J].Chinese Pharmacological Bulletin,2012,(08):944.
[4]乔进,窦志华,吴锋,等.灵芝多糖联合二甲双胍对2型糖尿病大鼠 心肌AGEs及CTGF的影响及其机制[J].中国药理学通报,2014,(04):536.
 QIAO Jin,DOU Zhi-hua,WU Feng,et al.Effect of combination of ganoderma lucidum polysaccharide and metformin on AGEs and CTGF of cardiac muscle in type 2 diabetic rats and the mechanism[J].Chinese Pharmacological Bulletin,2014,(08):536.
[5]姜华凤,曹水江,沈 峰,等.5-氨基乙酰丙酸辅助二甲双胍的降血糖作用[J].中国药理学通报,2014,(08):1127.
 JIANG Hua-feng,CAO Shui-jiang,SHEN Feng,et al.Study of 5-aminolevulinic acid in enhancing anti-diabetic efficacy of metformin[J].Chinese Pharmacological Bulletin,2014,(08):1127.
[6]李业琼,叶山东,翟丽敏,等.二甲双胍对2型糖尿病模型大鼠肾组织AGEs表达的影响[J].中国药理学通报,2016,(05):703.[doi:10.3969/j.issn.1001-1978.2016.05.021]
 LI Ye-qiong,YE Shan-dong,ZHAI Li-min,et al.Effects of metformin on expression of renal tissue AGEs in type 2 diabetic rats[J].Chinese Pharmacological Bulletin,2016,(08):703.[doi:10.3969/j.issn.1001-1978.2016.05.021]
[7]熊宗萍,朱 鹏,黄师琼,等.多药及毒素外排转运蛋白遗传药理学研究进展[J].中国药理学通报,2016,(12):1639.[doi:10.3969/j.issn.1001-1978.2016.12.003]
 XIONG Zong-ping,ZHU Peng,HUANG Shi-qiong,et al.Research progress on pharmacogenetics in multidrug and toxin extrusion proteins[J].Chinese Pharmacological Bulletin,2016,(08):1639.[doi:10.3969/j.issn.1001-1978.2016.12.003]
[8]葛安琪,殷红,李登峰,等.二甲双胍通过减少STAT3磷酸化缓解大鼠骨癌痛[J].中国药理学通报,2017,(06):844.[doi:10.3969/j.issn.1001-1978.2017.06.019]
 GE An-qi,YIN Hong,LI Deng-feng,et al.Metformin attenuates bone cancer pain by inhibiting expression of p-STAT3[J].Chinese Pharmacological Bulletin,2017,(08):844.[doi:10.3969/j.issn.1001-1978.2017.06.019]
[9]余 丹,叶山东,李业琼,等.二甲双胍对2型糖尿病模型大鼠肾功能及肾组织SIRT1表达的影响[J].中国药理学通报,2018,(05):615.[doi:10.3969/j.issn.1001-1978.2018.05.007]
 YU Dan,YE Shan-dong,LI Ye-qiong,et al.Effects of metformin on SIRT1 expression of renal tissues in type 2 diabetic rats[J].Chinese Pharmacological Bulletin,2018,(08):615.[doi:10.3969/j.issn.1001-1978.2018.05.007]
[10]邸志权,胡金芳,姜一朴,等.多柔比星、二甲双胍对干细胞心肌样分化的代谢组分研究[J].中国药理学通报,2018,(11):1560.[doi:10.3969/j.issn.1001-1978.2018.11.017]
 DI Zhi-quan,HU Jin-fang,JIANG Yi-pu,et al.Effects of doxorubicin and metformin on metabolic components of differentiation of stem cells into cardiomyocyte-like cells[J].Chinese Pharmacological Bulletin,2018,(08):1560.[doi:10.3969/j.issn.1001-1978.2018.11.017]
[11]乔 进,窦志华,吴 锋,等.灵芝多糖联合二甲双胍对2型糖尿病大鼠心肌结构及血流动力学的影响[J].中国药理学通报,2016,(07):1012.[doi:10.3969/j.issn.1001-1978.2016.07.024]
 QIAO Jin,DOU Zhi-hua,WU Feng,et al.Effects of Ganoderma lucidum polysaccharides combined with metformin on myocardial structure and hemodynamics in type 2 diabetic rats[J].Chinese Pharmacological Bulletin,2016,(08):1012.[doi:10.3969/j.issn.1001-1978.2016.07.024]

备注/Memo

备注/Memo:
收稿日期:2014-03-18,修回日期:2014-04-10
基金项目:科技部“十一五”国家科技支撑计划子课题项目(No 2006DAI06A20-02); 江苏省优势学科项目
作者简介:乔 进(1985-),男,硕士,主管药师,研究方向:心血管药理及临床药理学,E-mail:felix_jo@163.com; 窦志华(1966-),男,博士,主任中药师,硕士生导师,研究方向:中药药效物质基础及创新中药研究,通讯作者,Tel:0513-85116078,E-mail:zhihuadou@163.com
更新日期/Last Update: 1900-01-01