PMID- 30396095 OWN - NLM STAT- MEDLINE DCOM- 20190322 LR - 20190322 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 109 DP - 2019 Jan TI - Protective effects of Astragaloside IV on endoplasmic reticulum stress-induced renal tubular epithelial cells apoptosis in type 2 diabetic nephropathy rats. PG - 84-92 LID - S0753-3322(18)35523-9 [pii] LID - 10.1016/j.biopha.2018.10.041 [doi] AB - Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease (ESRD) worldwide. Renal tubular injury plays an important role in the development and progression of DN. And apoptosis of renal tubular epithelial cells (RTEC) contribute to the loss of renal function, increased levels of serum creatinine (SCr), blood urea nitrogen (BUN), urine total protein to urine creatinine and microalbuminuria and reduction of creatinine clear rate (CCr). Moreover, recent findings suggested that endoplasmic reticulum (ER) stress may lead to apoptosis of renal cells. Astragalosides IV (AS-IV) has a variety of pharmacological effects such as anti-apoptosis. Thus, in this study we investigated the effects and mechanisms of AS-IV on apoptosis of RTEC in high-fat diets (HFD) and low-dose streptozotocin (STZ)-induced type 2 DN rats. The results showed that AS-IV (40, 80 mg/kg) could alleviate RTEC apoptosis in DN rats. Furthermore, body weight, the majority of biochemical and renal function parameters and histopathological changes in the diabetic kidney were also improved by AS-IV. And AS-IV could reduce the expression of apoptosis-related proteins cleaved caspase-3, Bax/Bcl-2 ratio. ER stress-related proteins GRP78, p-PERK, ATF4 and CHOP were also inhibited by AS-IV in kidney of DN rats. Taken together, our study suggests that the protective effects of AS-IV may be related to inhibit ER stress-induced apoptosis through down-regulating the expression of p-PERK, ATF4 and CHOP. And our study provides a new theoretical basis for the clinical treatment of patients with kidney diseases. CI - Copyright (c) 2018. Published by Elsevier Masson SAS. FAU - Ju, Yinghui AU - Ju Y AD - Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Anhui Medical University, Hefei 230032, Anhui, China. FAU - Su, Yong AU - Su Y AD - Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Anhui Medical University, Hefei 230032, Anhui, China. FAU - Chen, Qingqing AU - Chen Q AD - Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Anhui Medical University, Hefei 230032, Anhui, China. FAU - Ma, Keke AU - Ma K AD - Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Anhui Medical University, Hefei 230032, Anhui, China. FAU - Ji, Tianjiao AU - Ji T AD - Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Anhui Medical University, Hefei 230032, Anhui, China. FAU - Wang, Zhongyuan AU - Wang Z AD - Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Anhui Medical University, Hefei 230032, Anhui, China. FAU - Li, Weizu AU - Li W AD - Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Anhui Medical University, Hefei 230032, Anhui, China. Electronic address: liweizu@126.com. FAU - Li, Weiping AU - Li W AD - Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Anhui Medical University, Hefei 230032, Anhui, China; Anqing Medical and Pharmaceutical College, Anqing 246052, Anhui, China. Electronic address: lwp19@126.com. LA - eng PT - Journal Article DEP - 20181102 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Atf4 protein, rat) RN - 0 (Ddit3 protein, rat) RN - 0 (Saponins) RN - 0 (Triterpenes) RN - 145891-90-3 (Activating Transcription Factor 4) RN - 147336-12-7 (Transcription Factor CHOP) RN - 3A592W8XKE (astragaloside A) RN - 5W494URQ81 (Streptozocin) RN - EC 2.7.11.1 (PERK kinase) RN - EC 2.7.11.1 (eIF-2 Kinase) SB - IM MH - Activating Transcription Factor 4/genetics MH - Animals MH - Apoptosis/drug effects MH - Diabetes Mellitus, Experimental/complications/*drug therapy MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Diabetic Nephropathies/*prevention & control MH - Dose-Response Relationship, Drug MH - Down-Regulation/drug effects MH - Endoplasmic Reticulum Stress/drug effects MH - Epithelial Cells/drug effects/metabolism MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - Saponins/*pharmacology MH - Streptozocin MH - Transcription Factor CHOP/genetics MH - Triterpenes/*pharmacology MH - eIF-2 Kinase/genetics OTO - NOTNLM OT - Apoptosis OT - Astragaloside IV OT - Diabetic nephropathy OT - Endoplasmic reticulum stress OT - Renal tubular epithelial cells EDAT- 2018/11/06 06:00 MHDA- 2019/03/23 06:00 CRDT- 2018/11/06 06:00 PHST- 2018/08/08 00:00 [received] PHST- 2018/10/09 00:00 [revised] PHST- 2018/10/09 00:00 [accepted] PHST- 2018/11/06 06:00 [pubmed] PHST- 2019/03/23 06:00 [medline] PHST- 2018/11/06 06:00 [entrez] AID - S0753-3322(18)35523-9 [pii] AID - 10.1016/j.biopha.2018.10.041 [doi] PST - ppublish SO - Biomed Pharmacother. 2019 Jan;109:84-92. doi: 10.1016/j.biopha.2018.10.041. Epub 2018 Nov 2.