红芪多糖对db/db小鼠糖尿病心肌病NF-κB/IKKβ信号通路的影响  

Effects of Hedysarum polybotrys polysacchcaide on NF-κB/IKKβ signaling pathway in db/db mice with diabetic cardiomyopathy

作　　者：张花治 金智生 孙金宁 邵晶 罗向霞[3] ZHANG Hua-zhi;JIN Zhi-sheng;SUN Jin-ning;SHAO Jing;LUO Xiang-xia(Clinical College of Traditional Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,Gansu Province,China;Department of Ophthalmology,Affiliated Hospital of Gansu University of Traditional Chinese Medicine,Lanzhou 730020,Gansu Province,China;Department of Ophthalmology,Gansu Provincial Hospital of Traditional Chinese Medicine,Lanzhou 730000,Gansu Province,China)

机构地区：[1]甘肃中医药大学中医临床学院,甘肃兰州730000 [2]甘肃中医药大学附属医院眼科,甘肃兰州730020 [3]甘肃省中医院眼科,甘肃兰州730000

出　　处：《中国临床药理学杂志》2024年第6期849-853,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金地区科学基金资助项目(81360538);甘肃省高等学校创新基金资助项目(2020A-082);甘肃中医药大学中医学一级学科“岐黄英才”导师专项基金资助项目(ZYXKSD-202208)。

摘　　要：目的观察红芪多糖(HPS)对糖尿病心肌病(DCM)db/db小鼠心肌组织核转录因子-κB(NF-κB)/IκB激酶β(IKKβ)信号通路的影响。方法将60只7周龄的雄性db/db小鼠随机分为模型组、对照组和低、中、高剂量实验组,每组12只;另取12只同周龄的db/m小鼠作为正常组。正常组和模型组均灌胃给予等剂量0.9%NaCl;低、中、高剂量实验组分别灌胃给予50、100、200 mg·kg^(-1) HPS混悬液;对照组灌胃给予4 mg·kg^(-1)罗格列酮混悬液。6组大鼠每天给药1次,连续灌胃8周。用酶联免疫吸附试验法检测心肌组织中肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的含量,用实时荧光定量聚合酶链反应法检测心肌组织中NF-κB和IKKβmRNA的表达水平,并分析NF-κB蛋白表达水平与TNF-α和IL-6含量的相关性。结果正常组、模型组、对照组和高剂量实验组的小鼠心肌组织中IL-6含量分别为(1.24±0.54)、(7.72±0.24)、(2.90±0.50)和(2.78±0.56)ng·L^(-1),TNF-α含量分别为(1.96±0.52)、(5.25±0.72)、(2.84±0.86)和(2.82±0.58)ng·L^(-1),NF-κB mRNA表达水平分别为1.00±0.00、3.35±0.81、2.05±0.44和1.67±0.22,IKKβmRNA表达水平分别为1.00±0.00、2.92±0.07、1.51±0.07和1.41±0.08;对照组和高剂量实验组的上述指标与模型组比较,在统计学上差异均有统计学意义(P<0.01,P<0.05)。NF-κB蛋白表达水平与IL-6、TNF-α含量均呈正相关,相关系数分别为0.866和0.740(均P<0.01)。结论HPS可减轻小鼠心肌病理损害,减缓心肌胶原沉积和间质纤维化,其主要作用机制可能是通过调控NF-κB/IKKβ信号通路的表达抑制炎症反应来发挥作用。Objective To investigate the effect of hedysarum polysacchcaide(HPS)on nuclear transcription factor-κB(NF-κB)/IκB kinase β(IKKβ)signaling pathway in cardiac tissue of db/db mice with diabetic cardiomyopathy(DCM).Methods Altogether 607-week-old male db/db mice were randomly divided into model group,control group and experimental-H,-M,-L groups,with 12 mice in each group.In addition,12 db/m mice of the same week age were selected as the normal group.Normal group and model group were given 0.9%NaCl by intragastric administration.Experimental-L,-M,-H groups were given 50,100 and 200 mg·kg^(-1) HPS suspension by intragastriction,respectively.Control group was given 4 mg·kg^(-1) rosiglitazone suspension by intragastric administration.Six groups of rats were given the drug once a day for 8 weeks.The contents of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in myocardial tissue were detected by enzyme-linked immunosorbent assay.The mRNA expression levels of NF-κB and IKKβin myocardial tissue were detected by real-time fluorescence quantitative polymerase chain reaction.The correlation between the expression of NF-κB protein and the content of TNF-α and IL-6 was analyzed.Results The contents of IL-6 in myocardial tissue of normal,model,control and experimental-H groups were(1.24±0.54),(7.72±0.24),(2.90±0.50)and(2.78±0.56)ng·L^(-1);the contents of TNF-α were(1.96±0.52),(5.25±0.72),(2.84±0.86)and(2.82±0.58)ng·L^(-1);the mRNA expression levels of NF-κB were 1.00±0.00,3.35±0.81,2.05±0.44 and 1.67±0.22;the mRNA expression levels of IKKβ were 1.00±0.00,2.92±0.07,1.51±0.07 and 1.41±0.08,respectively.Compared with the model group,the above indexes of the control and experimental-H groups were statistically significant(P<0.01,P<0.05).The expression of NF-κB protein was positively correlated with the content of IL-6 and TNF-α,and the correlation coefficients were 0.866 and 0.740(all P<0.01).Conclusion HPS can alleviate the damage of myocardial pathology in mice,reduce myocardial collagen d

关 键 词：红芪多糖 糖尿病心肌病 DB/DB小鼠 核转录因子-κB信号通路 IκB激酶β 病理形态 

分 类 号：R28[医药卫生—中药学]