α-硫辛酸改善初诊2型糖尿病患者循环内皮祖细胞水平
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摘要
背景:前期研究表明,初诊2型糖尿病患者已存在血管内皮功能障碍,α-硫辛酸作为一种抗氧化剂,广泛应用于糖尿病神经病变患者,而其能否改善初诊2型糖尿病患者循环内皮祖细胞的数量与功能,目前尚无这方面的研究。目的:探讨α-硫辛酸对初诊2型糖尿病患者循环内皮祖细胞水平的影响。方法:将50例初诊2型糖尿病患者在基础治疗的前提下,随机分为对照组20例和α-硫辛酸组30例,治疗前和治疗2周检测超氧化物歧化酶、谷胱甘肽过氧物酶、丙二醛、8-羟基脱氧鸟苷、三酰甘油、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇水平及内皮祖细胞数量,分析各指标在两组间的差异及相关性。结果与结论:(1)与治疗前比较,α-硫辛酸组治疗后内皮祖细胞数量、超氧化物歧化酶、谷胱甘肽过氧物酶活性显著增加(P <0.05),丙二醛、8-羟基脱氧鸟苷、三酰甘油、总胆固醇、低密度脂蛋白胆固醇显著降低(P <0.05),高密度脂蛋白胆固醇显著升高(P <0.05);(2)与治疗前比较,对照组治疗后三酰甘油、总胆固醇、低密度脂蛋白胆固醇显著下降(P <0.05),高密度脂蛋白胆固醇显著升高(P <0.05);(3)两组治疗前后的差值比较:α-硫辛酸组较对照组内皮祖细胞数量、超氧化物歧化酶、谷胱甘肽过氧物酶活性显著增加(P <0.05),丙二醛、8-羟基脱氧鸟苷含量显著降低(P <0.05);(4)以α-硫辛酸组治疗前后各指标的差值进行多元线性回归分析显示,谷胱甘肽过氧物酶、丙二醛是内皮祖细胞水平的影响因素;(5)结果表明,α-硫辛酸能够通过抗氧化应激增加初诊2型糖尿病患者循环内皮祖细胞水平。
BACKGROUND:Previous studies have shown that vascular endothelial dysfunction exists in patients with newly diagnosed type 2 diabetes.Alpha-lipoic acid is widely used as an antioxidant in patients with diabetic neuropathy. Can it improve the number of circulating endothelial progenitor cells in newly diagnosed type 2 diabetic patients? There is no such report.OBJECTIVE:To investigate the impact of α-lipoic acid on circulating endothelial progenitor cells in newly diagnosed type 2 diabetes mellitus.METHODS:Fifty newly diagnosed type 2 diabetes mellitus patients were randomly divided into control group(n=20) and alpha-lipoic acid group(n=30). Superoxide dismutase, glutathione peroxidase, malondialdehyde, 8-hydroxydeoxyguanosine, triacylglycerol, total cholesterol,low-density lipoprotein cholesterol, high-density lipoprotein cholesterol levels and number of endothelial progenitor cells were detected in the two groups before and 2 weeks after treatment. The differences and correlations between the two groups were analyzed.RESULTS AND CONCLUSION:In the alpha-lipoic acid group, the number of endothelial progenitor cells, superoxide dismutase, glutathione peroxidase and high-density lipoprotein cholesterol levels were significantly increased after treatment compared with the baseline(P < 0.05),while the levels of malondialdehyde, 8-hydroxydeoxyguanosine, triacylglycerol, total cholesterol and low-density lipoprotein cholesterol were significantly decreased after the treatment(P < 0.05). In the control group, the levels of triacylglycerol, total cholesterol and low-density lipoprotein cholesterol were significantly reduced after treatment compared with the baseline(P < 0.05), while the level of high-density lipoprotein cholesterol increased significantly after treatment(P < 0.05). Compared with the control group, the number of endothelial progenitor cells, superoxide dismutase and glutathione peroxidase levels were significantly increased in the alpha-lipoic acid group(P < 0.05),while the levels of malondialdehyde and 8-hydroxydeoxyguanosine were decreased in the alpha-lipoic acid group(P < 0.05). Multivariate linear regression analysis of the differences of the indexes before and after treatment in the alpha-lipoic acid group showed that the number of endothelial progenitor cells was correlated with the levels of glutathione peroxidase and malondialdehyde. To conclude, the treatment withα-lipoic acid increases the number of circulating endothelial progenitor cells in newly diagnosed type 2 diabetes mellitus, which is associated with antioxidative stress.
BACKGROUND:Previous studies have shown that vascular endothelial dysfunction exists in patients with newly diagnosed type 2 diabetes.Alpha-lipoic acid is widely used as an antioxidant in patients with diabetic neuropathy. Can it improve the number of circulating endothelial progenitor cells in newly diagnosed type 2 diabetic patients? There is no such report.OBJECTIVE:To investigate the impact of α-lipoic acid on circulating endothelial progenitor cells in newly diagnosed type 2 diabetes mellitus.METHODS:Fifty newly diagnosed type 2 diabetes mellitus patients were randomly divided into control group(n=20) and alpha-lipoic acid group(n=30). Superoxide dismutase, glutathione peroxidase, malondialdehyde, 8-hydroxydeoxyguanosine, triacylglycerol, total cholesterol,low-density lipoprotein cholesterol, high-density lipoprotein cholesterol levels and number of endothelial progenitor cells were detected in the two groups before and 2 weeks after treatment. The differences and correlations between the two groups were analyzed.RESULTS AND CONCLUSION:In the alpha-lipoic acid group, the number of endothelial progenitor cells, superoxide dismutase, glutathione peroxidase and high-density lipoprotein cholesterol levels were significantly increased after treatment compared with the baseline(P < 0.05),while the levels of malondialdehyde, 8-hydroxydeoxyguanosine, triacylglycerol, total cholesterol and low-density lipoprotein cholesterol were significantly decreased after the treatment(P < 0.05). In the control group, the levels of triacylglycerol, total cholesterol and low-density lipoprotein cholesterol were significantly reduced after treatment compared with the baseline(P < 0.05), while the level of high-density lipoprotein cholesterol increased significantly after treatment(P < 0.05). Compared with the control group, the number of endothelial progenitor cells, superoxide dismutase and glutathione peroxidase levels were significantly increased in the alpha-lipoic acid group(P < 0.05),while the levels of malondialdehyde and 8-hydroxydeoxyguanosine were decreased in the alpha-lipoic acid group(P < 0.05). Multivariate linear regression analysis of the differences of the indexes before and after treatment in the alpha-lipoic acid group showed that the number of endothelial progenitor cells was correlated with the levels of glutathione peroxidase and malondialdehyde. To conclude, the treatment withα-lipoic acid increases the number of circulating endothelial progenitor cells in newly diagnosed type 2 diabetes mellitus, which is associated with antioxidative stress.
引文
[1]Rao Kondapally Seshasai S,Kaptoge S,Thompson A,et al.Diabetes mellitus,fasting glucose,and risk of cause-specific death.N Engl J Med.2011;364(9):829-841.
[2]Bo S,Ciccone G,Gancia R,et al.Mortality within the first 10years of the disease in type 2 diabetic patients.Nutr Metab Cardiovasc Dis.2006;16(1):8-12.
[3]Lombardo MF,Iacopino P,Cuzzola M,et al.Type 2 diabetes mellitus impairs the maturation of endothelial progenitor cells and increases the number of circulating endothelial cells in peripheral blood.Cytometry A.2012;81(10):856-864.
[4]Russell JS,Brown JM.Circulating mouse Flk1+/c-Kit+/CD45-cells function as endothelial progenitors cells(EPCs)and stimulate the growth of human tumor xenografts.Mol Cancer.2014;13:177.
[5]Pías-Peleteiro J,Campos F,Castillo J,et al.Endothelial progenitor cells as a therapeutic option in intracerebral hemorrhage.Neural Regen Res.2017;12(4):558-561.
[6]Hamed S,Brenner B,Roguin A.Nitric oxide:a key factor behind the dysfunctionality of endothelial progenitor cells in diabetes mellitus type-2.Cardiovasc Res.2011;91(1):9-15.
[7]陈树春,宋光耀,孙阳,等.初诊2型糖尿病患者外周血内皮祖细胞的研究[J].天津医药,2010,38(7):549-551.
[8]夏文华,饶玉霞.2型糖尿病患者内皮祖细胞数量和功能研究[J].咸宁学院学报(医学版),2012,26(1):12-14.
[9]Asahara T,Masuda H,Takahashi T,et al.Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization.Circ Res.1999;85(3):221-228.
[10]Hristov M,Schmitz S,Nauwelaers F,et al.A flow cytometric protocol for enumeration of endothelial progenitor cells and monocyte subsets in human blood.J Immunol Methods.2012;381(1-2):9-13.
[11]Ma XL,Sun XL,Wan CY,et al.Significance of circulating endothelial progenitor cells in patients with fracture healing process.J Orthop Res.2012;30(11):1860-1866.
[12]Sen S,Mc Donald SP,Coates PT,et al.Endothelial progenitor cells:novel biomarker and promising cell therapy for cardiovascular disease.Clin Sci(Lond).2011;120(7):263-283.
[13]Zhou X,Patel D,Sen S,et al.Poly-ADP-ribose polymerase inhibition enhances ischemic and diabetic wound healing by promoting angiogenesis.J Vasc Surg.2017;65(4):1161-1169.
[14]Lin CP,Lin FY,Huang PH,et al.Endothelial progenitor cell dysfunction in cardiovascular diseases:role of reactive oxygen species and inflammation.Biomed Res Int.2013;2013:845037.
[15]Barton M.Prevention and endothelial therapy of coronary artery disease.Curr Opin Pharmacol.2013;13(2):226-241.
[16]Chen S,Sun L,Gao H,et al.Visfatin and oxidative stress influence endothelial progenitor cells in obese populations.Endocr Res.2015;40(2):83-87.
[17]陈树春,宋光耀,孙阳,等.2型糖尿病一级亲属内皮祖细胞与氧化应激[J].中华内科杂志,2012,51(3):197-200.
[18]陈树春,宋光耀.内皮祖细胞与氧化应激研究进展[J].中国组织工程研究与临床康复,2011,15(6):1119-1122.
[19]Chen DD,Dong YG,Yuan H,et al.Endothelin 1 activation of endothelin A receptor/NADPH oxidase pathway and diminished antioxidants critically contribute to endothelial progenitor cell reduction and dysfunction in salt-sensitive hypertension.Hypertension.2012;59(5):1037-1043.
[20]Kulikowska-Karpińska E,Czerw K.Estimation of8-hydroxy-2'-deoxyguanosine(8-OHdG)concentration in the urine of cigarette smokers.Wiad Lek.2015;68(1):32-38.
[21]Tabur S,Aksoy?N,Korkmaz H,et al.Investigation of the role of 8-OHdG and oxidative stress in papillary thyroid carcinoma.Tumour Biol.2015;36(4):2667-2674.
[22]Liu JT,Chen YL,Chen WC,et al.Role of pigment epithelium-derived factor in stem/progenitor cell-associated neovascularization.J Biomed Biotechnol.2012;2012:871272.
[23]Zaragoza C,Gomez-Guerrero C,Martin-Ventura JL,et al.Animal models of cardiovascular diseases.J Biomed Biotechnol.2011;2011:497841.
[24]Tousoulis D,Andreou I,Antoniades C,et al.Role of inflammation and oxidative stress in endothelial progenitor cell function and mobilization:therapeutic implications for cardiovascular diseases.Atherosclerosis.2008;201(2):236-247.
[25]Carracedo J,Merino A,Brice?o C,et al.Carbamylated low-density lipoprotein induces oxidative stress and accelerated senescence in human endothelial progenitor cells.FASEB J.2011;25(4):1314-1322.
[26]Pickering RJ,Rosado CJ,Sharma A,et al.Recent novel approaches to limit oxidative stress and inflammation in diabetic complications.Clin Transl Immunology.2018;7(4):e1016.
[27]Sasaki S,Inoguchi T.The role of oxidative stress in the pathogenesis of diabetic vascular complications.Diabetes Metab J.2012;36(4):255-261.
[28]Ceretta LB,Réus GZ,Abelaira HM,et al.Increased oxidative stress and imbalance in antioxidant enzymes in the brains of alloxan-induced diabetic rats.Exp Diabetes Res.2012;2012:302682.
[29]Hernández-Beltrán N,Moreno CB,Gutiérrez-álvarez AM.Contribution of mitochondria to pain in diabetic neuropathy.Endocrinol Nutr.2013;60(1):25-32.
[30]Rochette L,Ghibu S,Muresan A,et al.Alpha-lipoic acid:molecular mechanisms and therapeutic potential in diabetes.Can J Physiol Pharmacol.2015;93(12):1021-1027.
[31]陈树春,宋光耀,章冬梅,等.α-硫辛酸对高糖状态下内皮祖细胞的影响[J].细胞与分子免疫学杂志,2012,28(3):240-243.
[32]Zhao M,Chen JY,Chu YD,et al.Efficacy of epalrestat plusα-lipoic acid combination therapy versus monotherapy in patients with diabetic peripheral neuropathy:a meta-analysis of 20 randomized controlled trials.Neural Regen Res.2018;13(6):1087-1095.
[33]王景尚,孙明月,黄烨,等.α-硫辛酸对血糖波动状态下2型糖尿病大鼠血管内皮细胞功能及PI3K/Akt/GSK-3β通路的影响[J].中国全科医学,2017,20(24):2965-2971.
[2]Bo S,Ciccone G,Gancia R,et al.Mortality within the first 10years of the disease in type 2 diabetic patients.Nutr Metab Cardiovasc Dis.2006;16(1):8-12.
[3]Lombardo MF,Iacopino P,Cuzzola M,et al.Type 2 diabetes mellitus impairs the maturation of endothelial progenitor cells and increases the number of circulating endothelial cells in peripheral blood.Cytometry A.2012;81(10):856-864.
[4]Russell JS,Brown JM.Circulating mouse Flk1+/c-Kit+/CD45-cells function as endothelial progenitors cells(EPCs)and stimulate the growth of human tumor xenografts.Mol Cancer.2014;13:177.
[5]Pías-Peleteiro J,Campos F,Castillo J,et al.Endothelial progenitor cells as a therapeutic option in intracerebral hemorrhage.Neural Regen Res.2017;12(4):558-561.
[6]Hamed S,Brenner B,Roguin A.Nitric oxide:a key factor behind the dysfunctionality of endothelial progenitor cells in diabetes mellitus type-2.Cardiovasc Res.2011;91(1):9-15.
[7]陈树春,宋光耀,孙阳,等.初诊2型糖尿病患者外周血内皮祖细胞的研究[J].天津医药,2010,38(7):549-551.
[8]夏文华,饶玉霞.2型糖尿病患者内皮祖细胞数量和功能研究[J].咸宁学院学报(医学版),2012,26(1):12-14.
[9]Asahara T,Masuda H,Takahashi T,et al.Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization.Circ Res.1999;85(3):221-228.
[10]Hristov M,Schmitz S,Nauwelaers F,et al.A flow cytometric protocol for enumeration of endothelial progenitor cells and monocyte subsets in human blood.J Immunol Methods.2012;381(1-2):9-13.
[11]Ma XL,Sun XL,Wan CY,et al.Significance of circulating endothelial progenitor cells in patients with fracture healing process.J Orthop Res.2012;30(11):1860-1866.
[12]Sen S,Mc Donald SP,Coates PT,et al.Endothelial progenitor cells:novel biomarker and promising cell therapy for cardiovascular disease.Clin Sci(Lond).2011;120(7):263-283.
[13]Zhou X,Patel D,Sen S,et al.Poly-ADP-ribose polymerase inhibition enhances ischemic and diabetic wound healing by promoting angiogenesis.J Vasc Surg.2017;65(4):1161-1169.
[14]Lin CP,Lin FY,Huang PH,et al.Endothelial progenitor cell dysfunction in cardiovascular diseases:role of reactive oxygen species and inflammation.Biomed Res Int.2013;2013:845037.
[15]Barton M.Prevention and endothelial therapy of coronary artery disease.Curr Opin Pharmacol.2013;13(2):226-241.
[16]Chen S,Sun L,Gao H,et al.Visfatin and oxidative stress influence endothelial progenitor cells in obese populations.Endocr Res.2015;40(2):83-87.
[17]陈树春,宋光耀,孙阳,等.2型糖尿病一级亲属内皮祖细胞与氧化应激[J].中华内科杂志,2012,51(3):197-200.
[18]陈树春,宋光耀.内皮祖细胞与氧化应激研究进展[J].中国组织工程研究与临床康复,2011,15(6):1119-1122.
[19]Chen DD,Dong YG,Yuan H,et al.Endothelin 1 activation of endothelin A receptor/NADPH oxidase pathway and diminished antioxidants critically contribute to endothelial progenitor cell reduction and dysfunction in salt-sensitive hypertension.Hypertension.2012;59(5):1037-1043.
[20]Kulikowska-Karpińska E,Czerw K.Estimation of8-hydroxy-2'-deoxyguanosine(8-OHdG)concentration in the urine of cigarette smokers.Wiad Lek.2015;68(1):32-38.
[21]Tabur S,Aksoy?N,Korkmaz H,et al.Investigation of the role of 8-OHdG and oxidative stress in papillary thyroid carcinoma.Tumour Biol.2015;36(4):2667-2674.
[22]Liu JT,Chen YL,Chen WC,et al.Role of pigment epithelium-derived factor in stem/progenitor cell-associated neovascularization.J Biomed Biotechnol.2012;2012:871272.
[23]Zaragoza C,Gomez-Guerrero C,Martin-Ventura JL,et al.Animal models of cardiovascular diseases.J Biomed Biotechnol.2011;2011:497841.
[24]Tousoulis D,Andreou I,Antoniades C,et al.Role of inflammation and oxidative stress in endothelial progenitor cell function and mobilization:therapeutic implications for cardiovascular diseases.Atherosclerosis.2008;201(2):236-247.
[25]Carracedo J,Merino A,Brice?o C,et al.Carbamylated low-density lipoprotein induces oxidative stress and accelerated senescence in human endothelial progenitor cells.FASEB J.2011;25(4):1314-1322.
[26]Pickering RJ,Rosado CJ,Sharma A,et al.Recent novel approaches to limit oxidative stress and inflammation in diabetic complications.Clin Transl Immunology.2018;7(4):e1016.
[27]Sasaki S,Inoguchi T.The role of oxidative stress in the pathogenesis of diabetic vascular complications.Diabetes Metab J.2012;36(4):255-261.
[28]Ceretta LB,Réus GZ,Abelaira HM,et al.Increased oxidative stress and imbalance in antioxidant enzymes in the brains of alloxan-induced diabetic rats.Exp Diabetes Res.2012;2012:302682.
[29]Hernández-Beltrán N,Moreno CB,Gutiérrez-álvarez AM.Contribution of mitochondria to pain in diabetic neuropathy.Endocrinol Nutr.2013;60(1):25-32.
[30]Rochette L,Ghibu S,Muresan A,et al.Alpha-lipoic acid:molecular mechanisms and therapeutic potential in diabetes.Can J Physiol Pharmacol.2015;93(12):1021-1027.
[31]陈树春,宋光耀,章冬梅,等.α-硫辛酸对高糖状态下内皮祖细胞的影响[J].细胞与分子免疫学杂志,2012,28(3):240-243.
[32]Zhao M,Chen JY,Chu YD,et al.Efficacy of epalrestat plusα-lipoic acid combination therapy versus monotherapy in patients with diabetic peripheral neuropathy:a meta-analysis of 20 randomized controlled trials.Neural Regen Res.2018;13(6):1087-1095.
[33]王景尚,孙明月,黄烨,等.α-硫辛酸对血糖波动状态下2型糖尿病大鼠血管内皮细胞功能及PI3K/Akt/GSK-3β通路的影响[J].中国全科医学,2017,20(24):2965-2971.