目的探究加味芪黄饮治疗糖尿病肾病(DN)的作用及其机制。方法采用高脂饮食联合腹腔注射链脲佐菌素的方法制备DN大鼠模型,随机分为:正常组、模型组、加味芪黄饮低剂量组和高剂量组,低、高剂量组大鼠每日分别予加味芪黄饮400 mg/kg、800 m...目的探究加味芪黄饮治疗糖尿病肾病(DN)的作用及其机制。方法采用高脂饮食联合腹腔注射链脲佐菌素的方法制备DN大鼠模型,随机分为:正常组、模型组、加味芪黄饮低剂量组和高剂量组,低、高剂量组大鼠每日分别予加味芪黄饮400 mg/kg、800 mg/kg灌胃治疗。12周后检杀,留取大鼠血、尿标本测定24 h尿白蛋白(24 h UAlb)、血肌酐(Scr)、尿素氮(BUN)、空腹血糖(FBG)、空腹胰岛素(FIns)、胰岛素抵抗指数(HOMA-IR)等指标,观察肾组织病理改变并行系膜增生指数(MEI)评分,免疫组化观察肾组织中胰岛素受体(InsR)、胰岛素受体底物-1(IRS-1)、磷脂酰肌醇-3-激酶(PI3K)、葡萄糖转运体4(GLUT4)等蛋白表达。结果与正常组比较,模型组大鼠24 h UAlb、Scr、BUN、FBG、FIns、HOMA-IR均明显升高(P<0.01),肾小球肥大,肾小球基底膜、系膜细胞、系膜基质弥漫增生,MEI评分升高(P<0.01);低、高剂量组大鼠上述指标均较模型组降低(P<0.05),肾组织病理损伤及MEI评分均较模型组改善(P<0.05),均呈剂量依赖性。与正常组比较,模型组大鼠肾组织中InsR、IRS-1、PI3K、GLUT4等蛋白表达下调(P<0.05);低、高剂量组大鼠上述蛋白表达均较模型组升高(P<0.05),且随药物剂量增加其升高趋势更明显。结论加味芪黄饮能延缓DN进展,其机制可能是通过激活InsR/IRS-1/PI3K/GLUT4通路,改善胰岛素抵抗状态发挥作用。展开更多
To the Editor:Childhood obesity is a serious public health concern that can have long-term impacts on physical and psychological health.Lifestyle interventions have been widely used to treat childhood obesity.Notably,...To the Editor:Childhood obesity is a serious public health concern that can have long-term impacts on physical and psychological health.Lifestyle interventions have been widely used to treat childhood obesity.Notably,individual responses to the same intervention differ by genetic background.Previous researchers have explored the moderating effects of several glucose-metabolism-related genes on childhood obesity interventions,including TCF7L2[1]and RPTOR.[2]Nevertheless,these studies have been limited in study designs(without a control group)and duration(no more than a year),and no studies have explored the effect of the INSR(another glucose-metabolism-related gene)variants.Moreover,previous studies have focused only on single nucleotide polymorphism(SNP)-based analyses instead of gene-based analyses on the present topic.As such,we examined the associations of the INSR gene variants with the response to lifestyle-based obesity intervention in Chinese children aged 8-10 years at both gene-and SNP-levels.展开更多
文摘目的探究加味芪黄饮治疗糖尿病肾病(DN)的作用及其机制。方法采用高脂饮食联合腹腔注射链脲佐菌素的方法制备DN大鼠模型,随机分为:正常组、模型组、加味芪黄饮低剂量组和高剂量组,低、高剂量组大鼠每日分别予加味芪黄饮400 mg/kg、800 mg/kg灌胃治疗。12周后检杀,留取大鼠血、尿标本测定24 h尿白蛋白(24 h UAlb)、血肌酐(Scr)、尿素氮(BUN)、空腹血糖(FBG)、空腹胰岛素(FIns)、胰岛素抵抗指数(HOMA-IR)等指标,观察肾组织病理改变并行系膜增生指数(MEI)评分,免疫组化观察肾组织中胰岛素受体(InsR)、胰岛素受体底物-1(IRS-1)、磷脂酰肌醇-3-激酶(PI3K)、葡萄糖转运体4(GLUT4)等蛋白表达。结果与正常组比较,模型组大鼠24 h UAlb、Scr、BUN、FBG、FIns、HOMA-IR均明显升高(P<0.01),肾小球肥大,肾小球基底膜、系膜细胞、系膜基质弥漫增生,MEI评分升高(P<0.01);低、高剂量组大鼠上述指标均较模型组降低(P<0.05),肾组织病理损伤及MEI评分均较模型组改善(P<0.05),均呈剂量依赖性。与正常组比较,模型组大鼠肾组织中InsR、IRS-1、PI3K、GLUT4等蛋白表达下调(P<0.05);低、高剂量组大鼠上述蛋白表达均较模型组升高(P<0.05),且随药物剂量增加其升高趋势更明显。结论加味芪黄饮能延缓DN进展,其机制可能是通过激活InsR/IRS-1/PI3K/GLUT4通路,改善胰岛素抵抗状态发挥作用。
基金supported by grants from the National Natural Science Foundation of China(Nos.82373694,81903343)Young Elite Scientists Sponsorship Program by CAST(2023QNRC001)+1 种基金Beijing Office for Education Sciences Planning(No.BECA23111)the Fundamental Research Funds for the Central Universities(No.BMU2021YJ030)
文摘To the Editor:Childhood obesity is a serious public health concern that can have long-term impacts on physical and psychological health.Lifestyle interventions have been widely used to treat childhood obesity.Notably,individual responses to the same intervention differ by genetic background.Previous researchers have explored the moderating effects of several glucose-metabolism-related genes on childhood obesity interventions,including TCF7L2[1]and RPTOR.[2]Nevertheless,these studies have been limited in study designs(without a control group)and duration(no more than a year),and no studies have explored the effect of the INSR(another glucose-metabolism-related gene)variants.Moreover,previous studies have focused only on single nucleotide polymorphism(SNP)-based analyses instead of gene-based analyses on the present topic.As such,we examined the associations of the INSR gene variants with the response to lifestyle-based obesity intervention in Chinese children aged 8-10 years at both gene-and SNP-levels.
