文献类型：期刊文献

中文题名：红芪多糖对糖尿病胃轻瘫大鼠氧化应激的影响

英文题名：Effects of Hedysarum Polybotrys Polysacchcaide on Oxidative Stress in Diabetic Gastroparesis Rats

作者：郭倩[1];李雅琪[2];万生芳[1];魏昭晖[1];杨蕤[1];李荣科[1];张磊[1];舒畅[1];李亚玲[1];杨雅丽[1]

第一作者：郭倩

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]中国药科大学,江苏南京211298

第一机构：甘肃中医药大学

年份：2023

卷号：30

期号：1

起止页码：114

中文期刊名：中国中医药信息杂志

外文期刊名：Chinese Journal of Information on Traditional Chinese Medicine

收录：CSTPCD;;CSCD:【CSCD_E2023_2024】；

基金：国家自然科学基金(82060914、81560718);甘肃省中医药管理局科研项目(GZK-2017-3);甘肃省中医药研究中心专项(zyzx-2020-zx11);甘肃中医药大学研究生创新基金(2021CX37)。

语种：中文

中文关键词：糖尿病胃轻瘫;红芪多糖;氧化应激;Keap1/Nrf2信号通路

外文关键词：diabetic gastroparesis;hedysarum polybotrys polysacchcaide;oxidative stress;Keap1/Nrf2 signaling pathway

摘要：目的研究红芪多糖对糖尿病胃轻瘫(DGP)大鼠氧化应激的影响,探讨其改善DGP的作用机制。方法72只雄性Wistar大鼠随机分空白组12只和造模组60只,造模组采用一次性大剂量腹腔注射链脲佐菌素联合高糖高脂饲料不规则喂养制备DGP模型。将成模大鼠随机分为模型组、阳性药组和红芪多糖高、中、低剂量组,阳性药组予枸橼酸莫沙必利3.5 mg/kg灌胃,红芪多糖高、中、低剂量组予红芪多糖溶液200、100、50 mg/kg灌胃,空白组和模型组予等体积纯净水灌胃,每日1次,连续8周。观察大鼠一般状况,测定胃排空及小肠推进率;ELISA检测血清活性氧(ROS)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、8-羟基脱氧鸟苷酸(8-OHdG)含量;HE染色观察小肠组织病理变化;qRT-PCR检测小肠组织Kelch样环氧氯丙烷相关蛋白-1(Keap1)、核因子E2相关因子(Nrf2)、血红素加氧酶-1(HO-1)和硫氧还蛋白(Trx)mRNA表达;Western blot检测小肠组织谷胱甘肽转移酶(GST)和醌氧化还原酶1(NQO1)蛋白表达。结果与空白组比较,模型组大鼠一般状况较差,随机血糖显著升高(P<0.01),体质量、胃排空率、小肠推进率均显著降低(P<0.01),血清ROS、MDA、8-OHdG含量显著增加(P<0.05,P<0.01),SOD含量显著减少(P<0.01);小肠组织腺体结构破坏,黏膜消失,有大量炎性细胞浸润,小肠组织Keap1 mRNA表达显著升高(P<0.01),Nrf2、HO-1、Trx mRNA及GST、NQO1蛋白表达显著降低(P<0.01)。与模型组比较,各给药组大鼠一般状况好转,随机血糖显著降低(P<0.01),红芪多糖高剂量组和阳性药组大鼠体质量、胃排空率、小肠推进率显著升高(P<0.01),血清ROS、MDA、8-OHdG含量显著减少(P<0.05,P<0.01),SOD含量显著增加(P<0.05,P<0.01);小肠黏膜损伤程度明显减轻,腺体结构逐渐完整,小肠组织Keap1 mRNA表达显著降低(P<0.01),Nrf2、HO-1、Trx mRNA及GST、NQO1蛋白表达显著升高(P<0.05,P<0.01)。结论红芪多糖可通过控制血糖,促进胃排空,改善氧化应激反应及修复小肠黏膜损伤,发挥改善DGP作用。
Objective To study the effects of hedysarum polybotrys polysacchcaide(HPS)on oxidative stress in diabetic gastroparesis(DGP)rats;To explore its mechanism for DGP.Methods Totally 72 male Wistar rats were randomly divided into blank group(12 rats)and modeling group(60 rats).The modeling group used a one-time highdosage intraperitoneal injection of streptozotocin combined with irregular feeding of high-sugar and high-fat feed to prepare the DGP model.The model rats were randomly divided into model group,positive drug group and HPS high-,medium-and low-dosage groups.The positive drug group was given 3.5 mg/kg of mosapride by gavage,and the HPS high-,medium-and low-dosage groups were given HPS 200,100,and 50 mg/kg by gavage,respectively,the blank group and model group were given the same amount of purified water by gavage,once a day for 8 consecutive weeks.The general condition of the rats were observed,and the gastric emptying rate and small intestinal propulsion rate were measured;ELISA was used to detect the contents of serum reactive oxygen species(ROS),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA),8-hydroxydeoxyguanylate(8-OHdG);HE staining was used to observe the pathological changes of small intestine tissue;qRT-PCR was used to detect Kelch-like epichlorohydrin-related protein-1(Keap1),nuclear factor E2-related factor(Nrf2),heme oxygenase-1(HO-1)and Thioredoxin(Trx)mRNA expression in small intestine tissue;Western blot was used to detect the protein expressions of glutathione transferase(GST)and quinone oxidoreductase 1(NQO1)in small intestinal tissue.Results Compared with the blank group,the general condition of the rats in the model group became worse,the random blood glucose increased significantly(P<0.01),the body weight,gastric emptying rate,and small intestinal propulsion rate significantly decreased(P<0.01),the contents of serum ROS,8-OHdG and MDA significantly increased(P<0.05,P<0.01),the content of SOD reduced significantly(P<0.01);the glandular structure of small intestine tissue was destroyed,the mucosa disappeared,and a large number of inflammatory cells infiltrated,the Keap1 mRNA expression in small intestine tissue significantly increased(P<0.01),and the expressions of Nrf2,HO-1,Trx mRNA and GST and NQO1 protein significantly decreased(P<0.01).Compared with the model group,the general condition of each administration group improved,and the random blood glucose decreased significantly(P<0.01),the body weight,gastric emptying rate and small intestinal propulsion rate of rats in the HPS high-dosage group and the positive drug group significantly increased(P<0.01),the contents of serum ROS,8-OHdG and MDA significantly reduced(P<0.05,P<0.01),and the content of SOD significantly increased(P<0.05,P<0.01);the damage degree of small intestinal mucosa was significantly alleviated,the glandular structure was gradually completed,the Keap1 mRNA expression in small intestinal tissue significantly decreased(P<0.01),and the expressions of Nrf2,HO-1,Trx mRNA and GST and NQO1 protein significantly increased(P<0.05,P<0.01).Conclusion HPS can play a role in improving DGP by controlling blood glucose,promoting gastric emptying,improving oxidative stress response and repairing small intestinal mucosal damage.