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,IKKβ mRNA 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 60 7-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 IKKβ in 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 I.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 deposition and fibrosis,its mechanism may be through regulating the expression of NF-κB/IKKβ signaling pathway to play a role in inhibiting the inflammatory reaction.
张花治;金智生;孙金宁;邵晶;罗向霞
甘肃中医药大学中医临床学院,甘肃兰州 730000||甘肃中医药大学 附属医院眼科,甘肃兰州 730020甘肃中医药大学中医临床学院,甘肃兰州 730000甘肃省中医院眼科,甘肃兰州 730000
中医学
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
Hedysarum polybotrys polysacchcaide;diabetic cardiomyopathy;db/db mice;nuclear transcription factor-κB signaling pathway;IκB kinase β;pathological morphology
《中国临床药理学杂志》 2024 (006)
849-853 / 5
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)
10.13699/j.cnki.1001-6821.2024.06.014
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