红芪多糖对db/db小鼠糖尿病心肌病心肌组织氧化应激的影响
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摘要
目的:研究红芪多糖(HPS)对调控db/db小鼠糖尿病心肌病(DCM)心肌组织中抗氧化基因表达的影响。方法:60只db/db小鼠随机平均分为5组:对照组,模型组,红芪多糖(HPS)高、中、低剂量组;正常组为12只同周龄同背景的雄性db/m小鼠。连续灌胃干预8周。检测血脂及心肌组织中丙二醛(MDA)含量;蛋白印记法和反转录聚合酶链式反应法检测小鼠心肌组织Nrf2以及其下游血红素加氧酶-1(HO-1)、谷胱甘肽还原酶(GR)、氨酰半胱氨酸合成酶催化亚单位(GCLC)mRNA和蛋白的表达。结果:药物治疗8周后,与模型组比较,各给药组的MDA含量均显著下降(P<0.01,P<0.05);HPS高、中剂量组及对照组Nrf2、HO-1蛋白表达显著升高(P<0.01),各给药组GCLC、GR蛋白表达均显著升高(P<0.01,P<0.05);HPS高、中剂量组及对照组Nrf2、GCLCmRNA表达显著升高(P<0.01),各给药组HO-1、GRmRNA表达均显著升高(P<0.01)。结论:HPS可能通过增加Nrf2的表达影响抗氧化酶类的表达,从而调控氧化应激改善db/db小鼠DCM心肌损伤。
Objective: To study the effects of Hedysarum polybotys saccharide(HPS) on the expression of antioxidant genes in myocardial tissue of diabetic cardiomyopathy in db/db mice. Methods: According to the weight, 60 db/db mice were randomly divided into 5 groups: Hedysarum polybotys saccharide high, medium and low dose experimental group, control group, model group; normal group were 12 male db/m mice of the same age and background. They were continuous intragastric intervention for 8 weeks. Detection of blood lipids and malondialdehyde in myocardial tissue(MDA) content; protein imprinting and reverse transcription polymerase chain reaction assay for detection the expression of Nrf2 and protein in the downstream such as HO-1, GR, GCLC mRNA in mouse myocardial tissue. Results: After 8-week treatment, compared with the model group, MDA content in each drug intervention group decreased significantly(P<0.01, P<0.05). The expression of Nrf2 and HO-1 protein in the HPS high and medium dose groups and the control group were significantly increased(P<0.01), and the expressions GCLC and GR protein in each drug intervention group were significantly increased(P<0.01, P<0.05), the expressions of Nrf2 and GCLC mRNA in the HPS high and medium dose groups and the control group were significantly increased(P<0.01), and the expressions of HO-1 and GR mRNA in each drug intervention group were significantly increased(P<0.01). Conclusion: HPS may improve the regulation of oxidative stress in db/db mice myocardial DCM by increasing the expression of Nrf2 to affect the expression of antioxidant enzyme.
Objective: To study the effects of Hedysarum polybotys saccharide(HPS) on the expression of antioxidant genes in myocardial tissue of diabetic cardiomyopathy in db/db mice. Methods: According to the weight, 60 db/db mice were randomly divided into 5 groups: Hedysarum polybotys saccharide high, medium and low dose experimental group, control group, model group; normal group were 12 male db/m mice of the same age and background. They were continuous intragastric intervention for 8 weeks. Detection of blood lipids and malondialdehyde in myocardial tissue(MDA) content; protein imprinting and reverse transcription polymerase chain reaction assay for detection the expression of Nrf2 and protein in the downstream such as HO-1, GR, GCLC mRNA in mouse myocardial tissue. Results: After 8-week treatment, compared with the model group, MDA content in each drug intervention group decreased significantly(P<0.01, P<0.05). The expression of Nrf2 and HO-1 protein in the HPS high and medium dose groups and the control group were significantly increased(P<0.01), and the expressions GCLC and GR protein in each drug intervention group were significantly increased(P<0.01, P<0.05), the expressions of Nrf2 and GCLC mRNA in the HPS high and medium dose groups and the control group were significantly increased(P<0.01), and the expressions of HO-1 and GR mRNA in each drug intervention group were significantly increased(P<0.01). Conclusion: HPS may improve the regulation of oxidative stress in db/db mice myocardial DCM by increasing the expression of Nrf2 to affect the expression of antioxidant enzyme.
引文
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[2]Battiprolu P K,Hoiayev B,Jiang N,et al.Metabolic stress-induced activation of FoxO1 triggers diabetic cardiomyopathy in mice.The Journal of Clinical Investigation,2012,122(3):1109-1118
[3]LI J,Ichikawa T,Janicki J S,et al.Targeting the Nrf2 pathway against cardiovascular disease.Expert Opinion on Therapeutic Targets,2009,13(7):785-794
[4]Nguyen T,Nioi P,Pickett C B.The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress.The Journal of Biological Chemistry,2009,284(20):13291-13295
[5]吴静,王华旻,李晶,等.db/db小鼠的实验室应用.生理科学进展,2013,44(1):12-18
[6]周嘉,寻英,黄松,等.复方丹参滴丸对2型糖尿病大鼠模型胰岛β细胞功能的影响.中成药,2015,37(8):1807-1810
[7]张哲,王超.KLF4在糖尿病小鼠心肌组织的表达及通心络胶囊干预作用的研究.中国药理学通报,2015,31(6):876-881
[8]CHEN J,ZHANG Z,CAI L.Diabetic cardiomyopathy and its prevention by nrf2:Current status.Diabetes&Metabolism Journal,2014,38(5):337-345
[9]Sousa B C,Pitt A R,Spickett C M.Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds.Free Radical Biology&Medicine,2017,111:294-308
[10]冷雪,谷艳丽,朱芳.2型糖尿病中医证型流行病学调查及其中医病因病机初探.中华中医药杂志,2015,30(3):734-735
[11]杨秀娟,李硕,杨志军,等.甘肃不同产地红芪的HPLC指纹图谱及化学模式识别.中华中医药杂志,2018,33(7):3070-3073
[12]郝丽晓,窦爱兰,高天爱.红芪与黄芪不同成分的研究.山西医科大学学报,1999(S1):27-28