{"title":"紫草素通过激活SIRT1/Nrf2/HO-1通路，抑制内质网应激诱导的细胞凋亡，减轻肾缺血再灌注损伤。","authors":"Qian Huang, Zilu Shi, Dandan Zheng, Huiqin Chen, Qiuhong Huang","doi":"10.1159/000542417","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Shikonin is the major bioactive compound abundant in Lithospermum erythrorhizon and possesses diverse pharmacological properties. This study aimed to examine shikonin roles in experimental renal ischemia/reperfusion (I/R) injury.</p><p><strong>Methods: </strong>Renal tissues and blood were collected from experimental renal I/R injury models. Kidney functions, structural injuries, and cellular death were assessed. Markers of endoplasmic reticulum (ER) stress were evaluated by RT-qPCR and Western blotting. The effect of shikonin on Sirt1/Nrf2/HO-1 signaling was detected by Western blotting and immunofluorescence staining. HK-2 cells that underwent hypoxia/reoxygenation (H/R) process were used to perform CCK-8 and flow cytometry.</p><p><strong>Results: </strong>For in vivo analysis, renal dysfunctions and tissue structural damage induced by I/R were relieved by shikonin. Additionally, shikonin alleviated ER stress-induced apoptosis in I/R mice. For in vitro analysis, shikonin inhibited ER stress-stimulated apoptosis of H/R cells. Mechanistically, shikonin activated Sirt1/Nrf2/HO-1 signaling post-I/R, and inhibition of Sirt1 limited shikonin-mediated protection against ER stress-stimulated apoptosis in both animal and cellular models.</p><p><strong>Conclusion: </strong>By activating Sirt1/Nrf2/HO-1 signaling, shikonin inhibits apoptosis caused by ER stress and relieves renal I/R injury.</p>","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"131-146"},"PeriodicalIF":2.3000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Shikonin Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis to Attenuate Renal Ischemia/Reperfusion Injury by Activating the Sirt1/Nrf2/HO-1 Pathway.\",\"authors\":\"Qian Huang, Zilu Shi, Dandan Zheng, Huiqin Chen, Qiuhong Huang\",\"doi\":\"10.1159/000542417\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Shikonin is the major bioactive compound abundant in Lithospermum erythrorhizon and possesses diverse pharmacological properties. This study aimed to examine shikonin roles in experimental renal ischemia/reperfusion (I/R) injury.</p><p><strong>Methods: </strong>Renal tissues and blood were collected from experimental renal I/R injury models. Kidney functions, structural injuries, and cellular death were assessed. Markers of endoplasmic reticulum (ER) stress were evaluated by RT-qPCR and Western blotting. The effect of shikonin on Sirt1/Nrf2/HO-1 signaling was detected by Western blotting and immunofluorescence staining. HK-2 cells that underwent hypoxia/reoxygenation (H/R) process were used to perform CCK-8 and flow cytometry.</p><p><strong>Results: </strong>For in vivo analysis, renal dysfunctions and tissue structural damage induced by I/R were relieved by shikonin. Additionally, shikonin alleviated ER stress-induced apoptosis in I/R mice. For in vitro analysis, shikonin inhibited ER stress-stimulated apoptosis of H/R cells. Mechanistically, shikonin activated Sirt1/Nrf2/HO-1 signaling post-I/R, and inhibition of Sirt1 limited shikonin-mediated protection against ER stress-stimulated apoptosis in both animal and cellular models.</p><p><strong>Conclusion: </strong>By activating Sirt1/Nrf2/HO-1 signaling, shikonin inhibits apoptosis caused by ER stress and relieves renal I/R injury.</p>\",\"PeriodicalId\":17813,\"journal\":{\"name\":\"Kidney & blood pressure research\",\"volume\":\" \",\"pages\":\"131-146\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Kidney & blood pressure research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000542417\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/11 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"PERIPHERAL VASCULAR DISEASE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kidney & blood pressure research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000542417","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/11 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
Shikonin Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis to Attenuate Renal Ischemia/Reperfusion Injury by Activating the Sirt1/Nrf2/HO-1 Pathway.
Introduction: Shikonin is the major bioactive compound abundant in Lithospermum erythrorhizon and possesses diverse pharmacological properties. This study aimed to examine shikonin roles in experimental renal ischemia/reperfusion (I/R) injury.
Methods: Renal tissues and blood were collected from experimental renal I/R injury models. Kidney functions, structural injuries, and cellular death were assessed. Markers of endoplasmic reticulum (ER) stress were evaluated by RT-qPCR and Western blotting. The effect of shikonin on Sirt1/Nrf2/HO-1 signaling was detected by Western blotting and immunofluorescence staining. HK-2 cells that underwent hypoxia/reoxygenation (H/R) process were used to perform CCK-8 and flow cytometry.
Results: For in vivo analysis, renal dysfunctions and tissue structural damage induced by I/R were relieved by shikonin. Additionally, shikonin alleviated ER stress-induced apoptosis in I/R mice. For in vitro analysis, shikonin inhibited ER stress-stimulated apoptosis of H/R cells. Mechanistically, shikonin activated Sirt1/Nrf2/HO-1 signaling post-I/R, and inhibition of Sirt1 limited shikonin-mediated protection against ER stress-stimulated apoptosis in both animal and cellular models.
Conclusion: By activating Sirt1/Nrf2/HO-1 signaling, shikonin inhibits apoptosis caused by ER stress and relieves renal I/R injury.
期刊介绍：
This journal comprises both clinical and basic studies at the interface of nephrology, hypertension and cardiovascular research. The topics to be covered include the structural organization and biochemistry of the normal and diseased kidney, the molecular biology of transporters, the physiology and pathophysiology of glomerular filtration and tubular transport, endothelial and vascular smooth muscle cell function and blood pressure control, as well as water, electrolyte and mineral metabolism. Also discussed are the (patho)physiology and (patho) biochemistry of renal hormones, the molecular biology, genetics and clinical course of renal disease and hypertension, the renal elimination, action and clinical use of drugs, as well as dialysis and transplantation. Featuring peer-reviewed original papers, editorials translating basic science into patient-oriented research and disease, in depth reviews, and regular special topic sections, ''Kidney & Blood Pressure Research'' is an important source of information for researchers in nephrology and cardiovascular medicine.
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