文献类型：期刊文献

中文题名：淫羊藿苷联合糖皮质激素对激素抵抗型肾病综合征模型大鼠的干预作用

英文题名：Intervention effects of icariin combined with glucocorticoid in rats of steroid-resistant nephrotic syndrome

作者：刘灿[1];戴恩来[1,2];丁照然[1];段淑文[1]

第一作者：刘灿

机构：[1]甘肃中医药大学中西医结合学院,甘肃兰州730030;[2]甘肃中医药大学附属医院肾病科,甘肃兰州730030

第一机构：甘肃中医药大学中西医结合学院

年份：2024

卷号：40

期号：13

起止页码：1913

中文期刊名：中国临床药理学杂志

外文期刊名：The Chinese Journal of Clinical Pharmacology

收录：CSTPCD;;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金资助项目(82160852);甘肃省教育厅优秀研究生“创新之星”基金资助项目(2023CXZX-738)。

语种：中文

中文关键词：淫羊藿苷;糖皮质激素;激素抵抗型肾病综合征;大鼠;钙/钙调素依赖性蛋白激酶-Ⅱα/丝切蛋白-1/F-肌动蛋白

外文关键词：icarin;glucocorticoid;steroid-resistant nephrotic syndrome;rat;calcium/calmodulin dependent protein kinase IIα/Cofilin-1/F-actin

摘要：目的探讨淫羊藿苷(ICA)联合醋酸泼尼松片(PAT)对激素抵抗型肾病综合征(SRNS)模型大鼠的干预作用。方法雄性SD大鼠用2次注射阿霉素(ADR)法构建SRNS模型。待建模成功后,随机分为模型组、PAT组、ICA组、联合组,每组10只;另取10只大鼠为空白组。空白组和模型组均给予0.9%NaCl;PAT组给予6.3 mg·kg^(-1)·d^(-1)PAT;ICA组给予50 mg·kg^(-1)·d^(-1)ICA;联合组给予6.3 mg·kg^(-1)·d^(-1)PAT+50 mg·kg^(-1)·d^(-1)ICA。5组大鼠灌胃体积均为1 mL·100 g^(-1),每天给药1次,共给药6周。比较各组大鼠的肾功能、血脂水平,用蛋白质印迹法检测钙/钙调素依赖性蛋白激酶-Ⅱα(CaMKⅡα)、丝切蛋白-1(Cofilin-1)和F-肌动蛋白(F-actin)的表达情况。结果空白组、模型组、PAT组、ICA组和联合组的第8周末尿蛋白定量分别为(6.66±1.48)、(178.38±8.96)、(161.56±5.49)、(157.13±8.32)和(96.90±5.05)mg·24 h^(-1),血清肌酸酐分别为(30.90±1.79)、(41.10±2.77)、(34.90±2.03)、(35.10±2.18)和(31.90±2.47)μmol·L^(-1),三酰甘油分别为(0.87±0.14)、(2.30±0.41)、(1.94±0.44)、(1.17±0.59)和(0.89±0.30)mmol·L^(-1),总胆固醇分别为(1.54±0.08)、(2.53±0.22)、(2.14±0.59)、(2.27±0.31)和(1.93±0.32)mmol·L^(-1),CaMKⅡα蛋白相对表达水平分别为0.88±0.09、0.65±0.06、0.71±0.08、0.76±0.07和0.88±0.08,p-Cofilin-1/Cofilin-1比值分别为0.56±0.27、2.52±0.04、0.75±0.02、0.91±0.20和0.53±0.05,F-actin蛋白相对表达水平分别为0.93±0.01、0.64±0.01、0.75±0.02、0.80±0.01和0.85±0.00。模型组的上述指标与空白组和联合组相比,在统计学上差异均有统计学意义(均P<0.05)。结论ICA联合PAT可通过调控CaMKⅡα/Cofilin-1/F-actin通路改善SRNS大鼠的肾功能、血脂水平,改善肾组织病理结构,促进骨架蛋白重构。
Objective To investigate the interventional effects of Icariin(ICA)combined with prednisone acetate tablets(PAT)in rats with steroid-resistant nephrotic syndrome(SRNS)model.Methods Male SD rats were used to construct the SRNS model with 2 injections of adriamycin(ADR),and were randomly divided into the model group,PAT group,ICA group,and the combined group,with 10 rats in each group after successful modeling;another 10 rats were taken as the blank group.The blank and model groups were given 0.9%NaCl;the PAT group was given 6.3 mg·kg^(-1)·d^(-1)PAT;the ICA group was given 50 mg·kg^(-1)·d^(-1)ICA;and the combined group was given 6.3 mg·kg^(-1)·d^(-1)PAT+50 mg·kg^(-1)·d^(-1)ICA.The volume of gavage of the five groups of rats was1 mL·100 g^(-1),and the drug was administered once a day for 6 weeks.The renal function and blood lipid level of rats in each group were compared;the expression of calcium/calmodulin dependent protein kinaseⅡα(CaMKⅡα),cofilin-1 and F-actin were detected by Western blotting.Results Urinary protein quantification values at 8 weeks in blank,model,PAT,ICA and combined groups were(6.66±1.48),(178.38±8.96),(161.56±5.49),(157.13±8.32)and(96.90±5.05)mg·24 h^(-1);serum creatinine levels were(30.90±1.79),(41.10±2.77),(34.90±2.03),(35.10±2.18)and(31.90±2.47)μmol·L^(-1);triglycerides levels were(0.87±0.14),(2.30±0.41),(1.94±0.44),(1.17±0.59)and(0.89±0.30)mmol·L^(-1);total cholesterol levels were(1.54±0.08),(2.53±0.22),(2.14±0.59),(2.27±0.31)and(1.93±0.32)mmol·L^(-1);the relative expression levels of CaMKⅡαproteins were 0.88±0.09,0.65±0.06,0.71±0.08,0.76±0.07 and 0.88±0.08;the p-Cofilin-1/Cofilin-1 ratios were 0.56±0.27,2.52±0.04,0.75±0.02,0.91±0.20 and 0.53±0.05;the relative expression levels of F-actin protein were 0.93±0.01,0.64±0.01,0.75±0.02,0.80±0.01 and0.85±0.00,respectively.The differences of the above indexes in the model group were statistically significant compared with those in the blank group and the combined group(all P<0.05).Conclusion ICA combined with PAT can improve renal function,lipid levels,improve renal histopathological structure,and promote skeletal protein remodeling in SRNS rats by regulating CaMKⅡα/Cofilin-1/F-actin pathway.