{"title":"黄芪甲苷IV通过调节SIRT6/HIF-1α轴抑制糖尿病肾病足细胞Pyroposis。","authors":"Mingyu Zhang, Wenyuan Liu, Yuxiang Liu, Ziyuan Zhang, Yaling Hu, Dalin Sun, Sufen Li, Jingai Fang","doi":"10.1089/dna.2023.0102","DOIUrl":null,"url":null,"abstract":"<p><p>To investigate the effect of astragaloside IV (AS) on podocytes pyroptosis in diabetic kidney disease (DKD). Forty male Sprague-Dawley rats were randomly divided into normal group (<i>n</i> = 10) and model group (<i>n</i> = 30). Rats in model group were intraperitoneally injected streptozotocin (60 mg/kg) for 3 days to induce DKD. Then rats were divided into DKD group, AS group, and UBCS group. The AS group was given 40 mg/kg/d of AS by gavage, and UBCS group was given 50 mg/kg/d of UBCS039 by gavage, and normal group and DKD group were given the same amount saline for 8 weeks, once a day. Hematoxylin-eosin and masson staining were used to observe pathology of kidney. Rat podocytes were divided into normal group, mannitol hypertonic group, high-glucose group, UBCS group, OSS group, and AS group. Western blotting, quantitative real-time polymerase chain reaction, immunofluorescence, and flow cytometry were used to analyze pyroptosis-related markers and reactive oxygen species (ROS) levels. Results showed that AS inhibited ROS and alleviated podocytes pyroptosis in rats by increasing expression of sirtuin 6 (SIRT6) and decreasing expression of hypoxia inducible factor 1 subunit alpha (HIF-1α). UBCS039 and AS enhanced SIRT6 level, decreased HIF-1α level, and finally improved pyroptosis of podocytes <i>in vitro</i>, whereas OSS-128167 showed the opposite effect for podocytes pyroptosis. AS improved podocytes pyroptosis in DKD by regulating SIRT6/HIF-1α pathway, thereby alleviating injury of DKD.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Astragaloside IV Inhibited Podocyte Pyroptosis in Diabetic Kidney Disease by Regulating SIRT6/HIF-1α Axis.\",\"authors\":\"Mingyu Zhang, Wenyuan Liu, Yuxiang Liu, Ziyuan Zhang, Yaling Hu, Dalin Sun, Sufen Li, Jingai Fang\",\"doi\":\"10.1089/dna.2023.0102\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>To investigate the effect of astragaloside IV (AS) on podocytes pyroptosis in diabetic kidney disease (DKD). Forty male Sprague-Dawley rats were randomly divided into normal group (<i>n</i> = 10) and model group (<i>n</i> = 30). Rats in model group were intraperitoneally injected streptozotocin (60 mg/kg) for 3 days to induce DKD. Then rats were divided into DKD group, AS group, and UBCS group. The AS group was given 40 mg/kg/d of AS by gavage, and UBCS group was given 50 mg/kg/d of UBCS039 by gavage, and normal group and DKD group were given the same amount saline for 8 weeks, once a day. Hematoxylin-eosin and masson staining were used to observe pathology of kidney. Rat podocytes were divided into normal group, mannitol hypertonic group, high-glucose group, UBCS group, OSS group, and AS group. Western blotting, quantitative real-time polymerase chain reaction, immunofluorescence, and flow cytometry were used to analyze pyroptosis-related markers and reactive oxygen species (ROS) levels. Results showed that AS inhibited ROS and alleviated podocytes pyroptosis in rats by increasing expression of sirtuin 6 (SIRT6) and decreasing expression of hypoxia inducible factor 1 subunit alpha (HIF-1α). UBCS039 and AS enhanced SIRT6 level, decreased HIF-1α level, and finally improved pyroptosis of podocytes <i>in vitro</i>, whereas OSS-128167 showed the opposite effect for podocytes pyroptosis. AS improved podocytes pyroptosis in DKD by regulating SIRT6/HIF-1α pathway, thereby alleviating injury of DKD.</p>\",\"PeriodicalId\":93981,\"journal\":{\"name\":\"DNA and cell biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"DNA and cell biology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1089/dna.2023.0102\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/9/25 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"DNA and cell biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1089/dna.2023.0102","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/25 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Astragaloside IV Inhibited Podocyte Pyroptosis in Diabetic Kidney Disease by Regulating SIRT6/HIF-1α Axis.
To investigate the effect of astragaloside IV (AS) on podocytes pyroptosis in diabetic kidney disease (DKD). Forty male Sprague-Dawley rats were randomly divided into normal group (n = 10) and model group (n = 30). Rats in model group were intraperitoneally injected streptozotocin (60 mg/kg) for 3 days to induce DKD. Then rats were divided into DKD group, AS group, and UBCS group. The AS group was given 40 mg/kg/d of AS by gavage, and UBCS group was given 50 mg/kg/d of UBCS039 by gavage, and normal group and DKD group were given the same amount saline for 8 weeks, once a day. Hematoxylin-eosin and masson staining were used to observe pathology of kidney. Rat podocytes were divided into normal group, mannitol hypertonic group, high-glucose group, UBCS group, OSS group, and AS group. Western blotting, quantitative real-time polymerase chain reaction, immunofluorescence, and flow cytometry were used to analyze pyroptosis-related markers and reactive oxygen species (ROS) levels. Results showed that AS inhibited ROS and alleviated podocytes pyroptosis in rats by increasing expression of sirtuin 6 (SIRT6) and decreasing expression of hypoxia inducible factor 1 subunit alpha (HIF-1α). UBCS039 and AS enhanced SIRT6 level, decreased HIF-1α level, and finally improved pyroptosis of podocytes in vitro, whereas OSS-128167 showed the opposite effect for podocytes pyroptosis. AS improved podocytes pyroptosis in DKD by regulating SIRT6/HIF-1α pathway, thereby alleviating injury of DKD.