文献类型：期刊文献

中文题名：基于NLRP3/Caspase-1/GSDMD通路对泼尼松联合淫羊藿苷提高激素抵抗型肾病综合征疗效的机制研究

英文题名：Prednisone combined with icariin enhances the therapeutic effect of steroid resistant nephrotic syndrome

作者：段淑文[1];魏亚君[2];武天凯[1];王晓辉[1];丁照然[1];刘灿[1];戴恩来[1]

第一作者：段淑文

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]中国人民解放军96604部队医院,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2024

卷号：29

期号：10

起止页码：1081

中文期刊名：中国临床药理学与治疗学

外文期刊名：Chinese Journal of Clinical Pharmacology and Therapeutics

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(82160852);甘肃省优秀研究生创新之星(2022CXZX-737)。

语种：中文

中文关键词：激素抵抗型肾病综合征;泼尼松;淫羊藿苷;NLRP3/caspase-1/GSDMD通路

外文关键词：steroid resistant nephrotic syndrome;prednisone;icariin;NLRP3/Caspase-1/GSDMD

摘要：目的:探讨泼尼松联合淫羊藿苷(icariin,ICA)对激素抵抗型肾病综合征(SRNS)的治疗作用及可能的分子机制。方法:体内实验用阿霉素建立大鼠模型,将大鼠分为空白组、模型组、泼尼松组(6.3 mg·kg^(-1)·d^(-1))、联合组(泼尼松6.3 mg·kg^(-1)·d^(-1)+淫羊藿苷50 mg·kg^(-1)·d^(-1)),各给药组分别予相应药物灌胃,连续6周。CBB法检测大鼠24小时尿蛋白;全自动血液生化分析仪检测大鼠白蛋白、总胆固醇、甘油三酯、肌酐、尿素氮;HE、Masson染色检测大鼠肾组织形态学变化;免疫组化及Western blot检测GR-α、GR-β、NLRP3、caspase-1、GSDMD的表达。体外实验用阿霉素诱导HK-2细胞损伤模型,分为空白组、模型组、联合组和NLRP3沉默组,Rt-PCR检测GR-α、GR-β、caspase-1、GSDMD mRNA的表达,Western blot检测GR-α、GR-β、caspase-1、GSDMD蛋白的表达。结果:体内实验中,与空白组比较,模型组大鼠的体质量减轻,24小时尿蛋白增多,白蛋白减少,总胆固醇、甘油三酯、肌酐、尿素氮升高,肾小管萎缩,肾间质区水肿,其中炎症细胞浸润明显,有纤维组织增生,肾组织中GR-β、NLRP3、caspase-1、GSDMD的水平上升,GR-α的水平降低(P<0.01);与模型组比较,联合组大鼠的体质量增加,24小时尿蛋白减少,白蛋白增多,总胆固醇、甘油三酯、肌酐、尿素氮降低,肾小管萎缩减轻,肾间质炎症细胞浸润减少,肾组织中GR-β、NLRP3、caspase-1、GSDMD的水平降低,GR-α的水平升高(P<0.01)。体外实验中,与空白组比较,模型组GR-β、caspase-1、GSDMD的mRNA及蛋白表达增加(P<0.01),GR-α的m RNA及蛋白表达降低(P<0.01);与模型组比较,联合组及NLRP3沉默组GR-β、caspase-1、GSDMD的mRNA及蛋白表达减少(P<0.01),GR-α的m RNA及蛋白表达增加(P<0.01)。结论:泼尼松联合ICA对SRNS大鼠的肾脏具有保护作用,可以提高SRNS大鼠的疗效,其机制可能与NLRP3/caspase-1/GSDMD通路相关。
AIM:To explore the therapeutic effect and possible molecular mechanisms of prednisone combined with icariin(ICA)on hormone resistant nephrotic syndrome(SRNS).METHODS:In the in vivo experiment,rats were divided into control group,SRNS group,prednisone group,and P+I group.Each group was given corresponding drugs for 6 weeks.Detection of 24-hour urinary protein in rats using CBB;The blood biochemistry analyzer detects rat albumin,total cholesterol,triglycerides,creatinine,and urea nitrogen;HE and Masson were used to detect morphological changes in rat kidney tissue;Immunohistochemical detection of GR-α,GR-β,NLRP3,caspase-1,GSDMD,IL-1β.In the in vitro experiment,HK-2 cell injury model with doxorubicin,divided into control group,SRNS group,prednisone group,P+I group.GR-α,GR-β,NLRP3,caspase-1,GSDMD were detected by Rt-PCR and Western blot.RESULTS:In the in vivo experiment,compared with the control group,the SRNS group showed weight loss,increased 24-hour urine protein,decreased albumin,increased total cholesterol,triglycerides,creatinine,and urea nitrogen,renal tubular atrophy,increased renal interstitial area,significant infiltration of inflammatory cells,fibrous tissue proliferation,and GR-β,NLRP3,caspase-1,GSDMD,IL-1βin renal tissue decreased(P<0.01);Compared with the SRNS group,the combined group showed weight gain,decreased 24-hour urine protein,increased albumin,decreased total cholesterol,triglycerides,creatinine,and urea nitrogen,reduced renal tubular atrophy,reduced interstitial inflammatory cell infiltration,reduced fibrosis,and and GR-α,NLRP3,caspase-1,GSDMD in renal tissue decreased increased(P<0.01).In vitro experiments,compared with the control group,the model group showed GR-β,NLRP3,caspase-1,and GSDMD increased(P<0.01),GR-αdecreased(P<0.01);Compared with the SRNS group,GR-β,NLRP3,caspase-1,and GSDMD decreased(P<0.01),GR-αincreased in the P+I group.CONCLUSION:The combination of prednisone and ICA has a protective effect on the kidneys of SRNS rats and can improve the therapeutic effect.The mechanism may be related to the NLRP3/Caspase-1/GSDMD pathway.