文章摘要
禹博威,潘晓琼,陈君第霞,等.黄芪多糖对糖尿病动脉粥样硬化大鼠糖脂代谢的影响及血管内皮保护机制[J].浙江中医药大学学报,2021,(5):447-453.
黄芪多糖对糖尿病动脉粥样硬化大鼠糖脂代谢的影响及血管内皮保护机制
Effect of Astragalus Polysaccharides on Glucose and Lipid Metabolism in Diabetic Atherosclerosis Rats and Vascular Endothelial Protection Mechanism
投稿时间:2020-10-20  
DOI:10.16466/j.issn1005-5509.2021.05.003
中文关键词: 黄芪多糖  糖尿病  动脉粥样硬化  一氧化氮  血管内皮功能障碍  AMPK信号通路  糖脂代谢
英文关键词: Astragalus polysaccharides  diabetes  atherosclerosis  nitric oxide  vascular endothelial dysfunction  AMPK signaling pathway  glucose and lipid metabolism
基金项目:温州市高层次人才创新项目(604090352/417);温州市基础性科研项目(Y20190716)
作者单位E-mail
禹博威 温州医科大学 浙江温州 325000  
潘晓琼 温州医科大学附属第二医院  
陈君第霞 温州医科大学 浙江温州 325000  
胡臻 温州医科大学附属第二医院 1435975104@qq.com 
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中文摘要:
      [目的]探讨黄芪多糖(Astragalus polysaccharides,APS)对糖尿病动脉粥样硬化大鼠糖脂代谢的影响及一氧化氮(nitric oxide,NO)相关的血管内皮保护机制。[方法]选择无特定病原体(specific pathogen free,SPF)级SD健康大鼠,采用高脂饮食+链脲佐菌素(streptozotocin,STZ)腹腔注射联合维生素D3(vitamin D3,VitD3)灌胃+免疫损伤法建立糖尿病动脉粥样硬化大鼠模型。将未造模的大鼠随机分为空白对照组、APS对照组,造模大鼠分为模型组、治疗组。模型组与治疗组以高脂饲料喂养,空白对照组与APS对照组以正常饲料喂养,模型组和空白对照组给予0.9%氯化钠溶液灌胃,APS对照组和治疗组给予APS 700mg·kg-1灌胃,共灌胃8周。观察记录大鼠健康状态,检测血清空腹血糖(fasting blood glucose,FBG)、空腹胰岛素(fasting serum insulin,FINS)、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)水平,并计算胰岛素抵抗指数(homeostatic model assessment of insulin resistance,HOMA-IR);采用苏木素-伊红(hematoxylin-eosin,HE)染色观察胸主动脉组织病理变化;实时荧光定量PCR(Real-time quantitative polymerase chain reaction,Real-time qPCR)检测胸主动脉组织内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)、烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(nicotinamide adenine dinucleotide phosphate oxidase 4,NOx4)、磷酸腺苷活化蛋白激酶(adenosine monophosphate-activated protein kinase,AMPK)的mRNA表达水平。[结果]与空白对照组比较,模型组大鼠一般情况欠佳,出现多食、多饮、多尿症状以及体重减少等现象,FBG、FINS水平及HOMA-IR升高(P<0.05,P<0.01),TC、TG、LDL-C水平增高,HDL-C水平降低(P<0.01)。HE染色显示胸主动脉内膜结构受损、钙盐沉积,伴泡沫细胞、炎性细胞浸润,并有斑块形成。Real-time qPCR提示胸主动脉中eNOS、AMPK mRNA表达下降(P<0.01),NOx4 mRNA表达增加(P<0.01)。APS对照组FBG、FINS、TC、TG、LDL-C、HDL-C、eNOS水平和HOMA-TR,AMPK mRNA、NOx4 mRNA差异不明显,均无统计学意义(P<0.05)。与模型组比较,治疗组大鼠一般情况改善,FBG、FINS水平及HOMA-IR降低(P<0.05),TC、TG、LDL-C降低(P<0.05),HDL-C水平差异无统计学意义(P<0.05)。HE染色显示胸主动脉内膜病变改善。胸主动脉组织中eNOS mRNA表达增高(P<0.05),NOx4 mRNA表达降低(P<0.05),AMPK mRNA表达增高(P<0.05)。[结论]APS能有效降低糖尿病动脉粥样硬化大鼠血糖、血脂水平,抑制糖尿病动脉粥样硬化形成,其机制可能与激活AMPK信号通路,活化eNOS以及抑制NOx4的表达有关,且APS对健康大鼠无明显影响。
英文摘要:
      [Objective]To investigate the effect of Astragalus polysaccharides(APS) on glucose and lipid metabolism and nitric oxide(NO) related vascular endothelial protection mechanism in diabetic atherosclerosis rats.[Methods] Healthy specific pathogen free(SPF) grade SD rats were selected to establish diabetic atherosclerotic rat modelby high-fat diet combined with streptozotocin(STZ) intraperitoneal injection+vitamin D3(VitD3) gavage+immune injury method.The unmodeled rats were randomly divided into blank control group and APS control group, model rats are divided into model group and treatment group. Rats in model group were given high-fat feed with the treatment group and rats in blank control group were given normal feed with the APS control group. Model group and blank control group were given 0.9% sodium chloride injection by gavage administration, while APS control group and treatment group were given 700mg·kg-1 APS, and all the groups were gavage administrated for 8 weeks. After 8 weeks, the health status were observed and recorded, levels of fasting blood glucose(FBG), fasting serum insulin(FINS), total cholesterol(TC), triglycerides(TG),low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C) were detected and homeostatic model assessment of insulin resistance(HOMA-IR) was calculated. Hematoxylin-eosin(HE) staining was used to observe the histopathological changes in the thoracic aorta; Real-time quantitative polymerase chain reaction(Real-time qPCR) was adopted to detect mRNA expression levels of endothelial nitric oxide synthase(eNOS), nicotinamide adenine dinucleotide phosphate oxidase 4(NOx4), and adenosine monophosphate-activated protein kinase(AMPK) in the thoracic aorta.[Results]Compared with blank control group, the rats in model group were generally worse off, showing symptoms of overeating, drinking, polyuria and weight loss, with increased levels of FBG, FINS and HOMA-IR(P<0.05,P<0.01), increased levels of TC, TG, LDL-C and decreased levels of HDL-C(P<0.01). HE staining revealed impaired thoracic aortic intimal structure with calcium salt deposition, foam cells, inflammatory cell infiltration, and plaque formation.Real-time qPCR showed that the expression of eNOS and AMPK mRNA in the thoracic aorta was decreased(P<0.01) and NOx4 mRNA expression was increased(P<0.01). There were no significant differences in levels of FBG, FINS, TC, TG, LDL-C, HDL-C, eNOS and HOMA-IR, AMPK mRNA and NOx4 mRNA in APS control group, and they were not statistically significant(P>0.05). Compared with model group, the general condition of rats in treatment group improved, the levels of FBG, FINS and HOMA-IR decreased significantly(P<0.05), while the levels of TC, TG, LDL-C decreased(P<0.05), and the difference of the level of HDL-C were not statistically significant(P>0.05). HE staining showed improvement in the endothelial lesion of the thoracic aorta.The expression of eNOS mRNA in thoracic aorta tissue increased(P<0.05), NOx4 mRNA decreased(P<0.05), and AMPK mRNA expression increased(P<0.05).[Conclusion]APS can effectively reduce blood glucose and lipid levels and inhibit diabetic atherosclerosis formation in rats, and the mechanisms may be related to activation of the AMPK signaling pathway, activation of eNOS and inhibition of NOx4 expression,but APS has no significant effect on healthy rats.
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