Astragaloside IV attenuates proteinuria in streptozotocin-induced diabetic nephropathy via the inhibition of endoplasmic reticulum stress

详细信息    查看全文

• 作者：Zeng Si Wang ; Fei Xiong ; Xiao Hang Xie ; Dan Chen ; Jian Hua Pan ; Li Cheng
• 关键词：Astragaloside IV ; Diabetic nephropathy ; Podocytes ; Proteinuria ; Endoplasmic reticulum stress ; Apoptosis
• 刊名：BMC Nephrology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：16
• 期：1
• 全文大小：1,269 KB
• 参考文献：1. Boer, IH, Rue, TC, Hall, YN, Heagerty, PJ, Weiss, NS, Himmelfarb, J (2011) Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA 305: pp. 2532-9 CrossRef
  2. Collins, AJ, Foley, RN, Chavers, B, Gilbertson, D, Herzog, C, Johansen, K (2012) 'United states renal data system 2011 annual data report: atlas of chronic kidney disease & end-stage renal disease in the United States. Am J Kidney Dis 59: pp. e1-420
  3. National Kidney, F (2012) KDOQI clinical practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis 60: pp. 850-86 CrossRef
  4. Nelson, RG, Tuttle, KR (2010) Prevention of diabetic kidney disease: negative clinical trials with renin-angiotensin system inhibitors. Am J Kidney Dis 55: pp. 426-30 CrossRef
  5. McAlpine, CS, Werstuck, GH (2013) The development and progression of atherosclerosis: evidence supporting a role for endoplasmic reticulum (ER) stress signaling. Cardiovasc Hematol Disord Drug Targets 13: pp. 158-64
  6. Saxena, S, Cabuy, E, Caroni, P (2009) A role for motoneuron subtype-selective ER stress in disease manifestations of FALS mice. Nat Neurosci 12: pp. 627-36 CrossRef
  7. Schonthal, AH (2012) Targeting endoplasmic reticulum stress for cancer therapy. Front Biosci 4: pp. 412-31 CrossRef
  8. McKimpson, WM, Weinberger, J, Czerski, L, Zheng, M, Crow, MT, Pessin, JE (2013) The apoptosis inhibitor ARC alleviates the ER stress response to promote beta-cell survival. Diabetes 62: pp. 183-93 CrossRef
  9. Lupachyk, S, Watcho, P, Stavniichuk, R, Shevalye, H, Obrosova, IG (2013) Endoplasmic reticulum stress plays a key role in the pathogenesis of diabetic peripheral neuropathy. Diabetes 62: pp. 944-52 CrossRef
  10. Lhotak, S, Sood, S, Brimble, E, Carlisle, RE, Colgan, SM, Mazzetti, A (2012) ER stress contributes to renal proximal tubule injury by increasing SREBP-2-mediated lipid accumulation and apoptotic cell death. Am J Physiol Renal Physiol 303: pp. F266-78 CrossRef
  11. Cunard, R, Sharma, K (2011) The endoplasmic reticulum stress response and diabetic kidney disease. Am J Physiol Renal Physiol 300: pp. F1054-61 CrossRef
  12. Luo, HM, Dai, RH, Li, Y (1995) [Nuclear cardiology study on effective ingredients of Astragalus membranaceus in treating heart failure]. Zhongguo Zhong Xi Yi Jie He Za Zhi 15: pp. 707-9
  13. He, Y, Du, M, Gao, Y, Liu, H, Wang, H, Wu, X (2013) Astragaloside IV attenuates experimental autoimmune encephalomyelitis of mice by counteracting oxidative stress at multiple levels. PLoS One 8: pp. e76495 CrossRef
  14. Zhang, N, Wang, XH, Mao, SL, Zhao, F (2011) Astragaloside IV improves metabolic syndrome and endothelium dysfunction in fructose-fed rats. Molecules 16: pp. 3896-907 CrossRef
  15. Gui, D, Huang, J, Guo, Y, Chen, J, Chen, Y, Xiao, W (2013) Astragaloside IV ameliorates renal injury in streptozotocin-induced diabetic rats through inhibiting NF-kappaB-mediated inflammatory genes expression. Cytokine 61: pp. 970-7 CrossRef
  16. Zheng, R, Deng, Y, Chen, Y, Fan, J, Zhang, M, Zhong, Y (2012) Astragaloside IV attenuates complement membranous attack complex induced podocyte injury through the MAPK pathway. Phytother Res 26: pp. 892-8 CrossRef
  17. Chen, Y, Deng, Y, Ni, Z, Chen, N, Chen, X, Shi, W (2013) Efficacy and safety of traditional chinese medicine (Shenqi particle) for patients with idiopathic membranous nephropathy: a multicenter randomized control
• 刊物主题：Nephrology; Internal Medicine;
• 出版者：BioMed Central
• ISSN：1471-2369

文摘

Background Diabetic nephropathy (DN) is a major cause of Chronic Kidney Disease and End-Stage Renal Disease throughout the world; however, the reversibility of diabetic nephropathy remains controversial. Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of DN. Astragaloside IV (AS-IV) is derived from Astragalus membranaceus (Fisch) Bge, a widely used traditional herbal medicine in China, and has diverse pharmacological activities including the attenuation of podocyte injury and amelioration of proteinuria in idiopathic nephrotic syndrome. The present study aimed to investigate the effect and mechanism of AS-IV on proteinuria in the rat streptozotocin (STZ)-induced model of diabetes. Methods Male Sprague–Dawley (SD) rats were randomly divided into four groups: normal control (Normal group), diabetic nephropathy (Model group), diabetic nephropathy plus AS-IV treatment (AS-IV group) and diabetic nephropathy plus 4-phenyl butyric acid treatment (PBA group). ER stress was induced in cultured human podocytes, pretreated with or without AS-IV, with tunicamycin (TM). At the end of 8?weeks, serum creatinine (Scr), blood urea nitrogen (BUN) and 24-hour urinary protein excretion rate (UAER) were determined. Renal morphology was examined after periodic acid-Schiff staining of kidney sections. Apoptosis of podocytes was measured by flow cytometry. The total expression and phosphorylation of eIF2α, PERK and JNK, and the expression of CHOP and cleaved caspase-3 were determined by western blotting. The expression of glucose-regulated protein 78 (GRP78) and 150?kDa oxygen-regulated protein (ORP150) mRNA and protein was determined by real-time PCR and western blotting respectively. Results AS-IV treatment significantly reduced urinary albumin excretion, plasma creatinine and blood urea nitrogen levels, and prevented the mesangial matrix expansion and increase in mean mesangial induced by STZ. AS-IV also prevented the phosphorylation of eIF2α, PERK and JNK, and inhibited the expression of GRP78 and ORP150 markedly, both in vivo and in vitro. AS-IV inhibited the TM-induced apoptosis of podocytes, concomitant with decreased CHOP expression and cleaved caspase-3. Conclusions This study supports the hypothesis that AS-IV reduces proteinuria and attenuates diabetes, which is associated with decreased ER stress. This might be an important mechanism in the renoprotective function of AS-IV in the pathogenesis of DN.