文献类型：期刊文献

中文题名：红芪多糖对db/db小鼠糖尿病心肌病心肌纤维化的改善作用

英文题名：Improvement of Hedysarum Polybotrys Polysacchcaide on myocardial fibrosis in db / db mice with diabetic cardiomyopathy

作者：张花治[1];金智生[1];王东旭[1];和彩玲[1];王栋[1];谢卓霖[1];楚惠媛[1];何流[1]

第一作者：张花治

机构：[1]甘肃中医药大学中医临床学院,兰州730000

第一机构：甘肃中医药大学中医临床学院

年份：2017

卷号：33

期号：3

起止页码：239

中文期刊名：中国临床药理学杂志

外文期刊名：The Chinese Journal of Clinical Pharmacology

收录：CSTPCD;;北大核心:【北大核心2014】；CSCD:【CSCD2017_2018】；

基金：国家自然科学基金地区科学基金资助项目(81360538);甘肃省青年科技基金计划基金资助项目(145RJYA297)

语种：中文

中文关键词：糖尿病心肌病;红芪多糖;db/db小鼠;超氧化物歧化酶;丙二醛;过氧化物酶体增殖物激活受体γ;核转录因子kappa;B

外文关键词：diabetic cardiomyopathy; Hedysarum Polybotrys Polysacchcaide; db / db mice; superoxide dismutase; malonaldehyde; peroxisome proliferator-activated receptor γ; nuclear transcription factor-kappa B

摘要：目的研究红芪多糖(HPS)对db/db小鼠糖尿病心肌病心肌纤维化的保护作用机制。方法按照体重将7周龄的雄性db/db小鼠随机分为5组(每组12只):高中低3个剂量实验组(HPS:200,100,50 mg·kg-1)、对照组(罗格列酮:4 mg·kg-1)及模型组(0.9%Na Cl);正常组为12只同周龄的db/m小鼠。连续灌胃8周。于干预前及干预后第2,4,6,8周末,检测血糖;干预第8周末,处死小鼠后分离血清,用生化法检测血脂及心肌组织超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)的活性;以Masson染色观察小鼠心肌组织纤维化程度;用q PCR法、免疫印迹法检测心肌组织过氧化物酶体增殖物激活受体γ(PPARγ)、核转录因子kappa B(NF-κB)mRNA和蛋白的表达。结果模型组、高中2个剂量实验组和对照组的SOD(mg·m L-1)分别为140.70±1.04,145.81±0.99,142.21±1.09,145.70±1.10;这4组的GSH-PX(U·mg-1)分别为110.91±0.82,114.94±0.78,112.10±0.86,114.84±0.86,与模型组比较,实验组与对照组活性显著增强,差异有统计学意义(均P<0.05)。这4组的MDA含量(nmol·mg-1)分别为7.20±0.49,5.82±0.52,6.62±0.67,5.80±0.52,与模型组比较,实验组与对照组活性显著降低,差异有统计学意义(均P<0.05)。模型组、高中低3个剂量实验组及对照组的心肌组织中PPARγmRNA表达分别为0.34±0.11,0.68±0.05,0.48±0.03,0.49±0.03,0.93±0.05;这5组的蛋白表达分别为0.75±0.12,1.78±0.08,1.44±0.07,1.07±0.05,1.63±0.02,与模型组比较,给药组的mRNA和蛋白表达均显著上调,差异有统计学意义(均P<0.05)。模型组、高中2个剂量实验组和对照组的心肌组织中NF-κB mRNA表达分别为3.35±0.81,1.67±0.22,2.34±0.39,2.05±0.44及蛋白表达分别为1.17±0.04,0.56±0.12,0.86±0.13,0.55±0.12,与模型组比较,给药组表达均显著下降,差异有统计学意义(P<0.05)。结论 HPS可能通过增加心肌PPARγ的表达,抑制NF-κB的活性,经PPARγ-NF-κB信号途径来控制氧化应激和炎症反应,从而减轻心肌纤维化的进展。
Objective To explore protection mechanism of Hedysari polysaccharide（ HPS） on myocardial fibrosis of db / db mice with diabetic cardiomyopathy. Methods Sixty db / db mice（ 7- week- old） were randomly divided into five groups： high- dose experimental group,middle- dose experimental group,low- dose experimental group（ HPS：200,100,50 mg·kg- 1）,control group（ rosiglitazone： 4 mg·kg- 1） and model group（ 0. 9% Na Cl,gavege）; while 12 db / m mice（ 7- week- old） were normal group. Each group had 12 mice. Blood glucose was detected at the baseline before intervention and at end of 2,4,6 and 8 weeks after intervention separately. The activity of blood lipid,superoxide dismutase（ SOD）,glutathione peroxidase（ GSH- Px） and the content of malondialdehyde（ MDA） were detected by biochemical method after 8 weeks. The degree of myocardial fibrosis was observed by masson staining. The q PCR method and Western blotting method were used to detect the expression of peroxisome proliferator- activated receptor γ（ PPARγ）,nuclear transcription factor- kappa B（ NF- κB） mRNA in myocardial tissue. Results The activities of SOD（ mg· m L- 1） in model group,high- dose experimental group,middle- dose experimental group,control group were 140. 70 ± 1. 04,145. 81 ± 0. 99,142. 21 ± 1. 09,145. 70 ± 1. 10,respectively with statistical difference compared with the model（ P〈0. 05）. The activities of GSH- PX（ U · mg- 1） in above four groups were 110. 91 ± 0. 82,114. 94 ± 0. 78,112. 10 ± 0. 86,114. 84 ± 0. 86 with statistical difference compared with the model（ all P〈0. 01）. The contents of MDA（ nmol·mg- 1） were 7. 20 ± 0. 49,5. 82 ± 0. 52,6. 62 ± 0. 67,5. 80 ± 0. 52 in the four groups which significantly decreased（ P〈0. 05,P〈0. 01）. The expression of PPARγ mRNA were 0. 34 ± 0. 11,0. 68 ± 0. 05,0. 48 ± 0. 03,0. 49 ± 0. 03,0. 93 ± 0. 05 and protein above were 0. 75 ± 0. 12,1. 78 ± 0. 08,1. 44 ± 0. 07,1. 07 ± 0. 05,1. 63 ± 0. 02 in above five groups with statistical difference compared with the model（ all P〈0. 05）. NF- kappa B mRNA were 3. 35 ± 0. 81,1. 67 ± 0. 22,2. 34 ± 0. 39,2. 05 ± 0. 44 and protein were 1. 17 ± 0. 04,0. 56 ± 0. 12,0. 86 ± 0. 13,0. 55 ± 0. 12 in the four groups with statistical difference compared with the model（ all P〈0. 05）. Conclusion HPS can reduce the development of myocardial fibrosis by increasing the expression of PPARγ and inhibiting the activity of NF- κB,controlling oxidative stress and inflammatory reaction through the PPARγ- NF- κB signaling pathway.