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首页> 外文期刊>Cellular Physiology and Biochemistry >Down-Regulation of PERK-ATF4-CHOP Pathway by Astragaloside IV is Associated with the Inhibition of Endoplasmic Reticulum Stress-Induced Podocyte Apoptosis in Diabetic Rats
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Down-Regulation of PERK-ATF4-CHOP Pathway by Astragaloside IV is Associated with the Inhibition of Endoplasmic Reticulum Stress-Induced Podocyte Apoptosis in Diabetic Rats

机译：黄芪甲苷IV下调PERK-ATF4-CHOP通路与抑制内质网应激诱导的足细胞凋亡有关。

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biBackground /i/bEndoplasmic reticulum (ER) stress-induced podocyte apoptosis plays a critical role in the development of diabetic nephropathy (DN). Here, we tested the hypothesis that suppression of PERK-ATF4-CHOP pathway by Astragaloside IV (AS-IV) is associated with inhibition of ER stress-induced podocyte apoptosis in streptozotocin (STZ)-induced diabetic rats. biMethods /i/bDiabetic rats were treated with AS-IV at 5 and 10 mg· kgsup-1/sup· dsup-1/sup, p.o., for 12 weeks. Albuminuria examination, hematoxylin & eosin staining and TUNEL analysis were performed. Immunohistochemistry, western blot, and real-time PCR were used to detect renal expression of ER chaperone GRP78 and ER-associated apoptosis proteins. biResults /i/bTreatment with AS-IV ameliorated albuminuria and renal histopathology in diabetic rats. Diabetic rats had significant increment in podocyte apoptosis as well as phosphorylated PERK and eIF2α in the kidneys, which were attenuated by AS-IV treatment. Furthermore, diabetic rats were found to have increased protein and mRNA expressions of GRP78 and ER-associated apoptosis proteins, such as ATF4, CHOP and TRB3, which were also attenuated by AS-IV treatment. Increased Bax expression and decreased Bcl-2 expression were detected in diabetic rats, and these changes were partially restored by AS-IV treatment. biConclusion /i/bThe protective effect of AS-IV on ER stress-induced podocyte apoptosis is associated with inhibition of PERK-ATF4-CHOP pathway. Down-regulation of PERK- ATF4-CHOP pathway by AS-IV may be a novel strategy for the treatment of DN.
机译：背景 内质网（ER）应激诱导的足细胞凋亡在糖尿病性肾病（DN）的发展中起关键作用。在这里，我们测试了一种假设，即黄芪甲苷IV（AS-IV）抑制PERK-ATF4-CHOP通路与抑制链脲佐菌素（STZ）诱导的糖尿病大鼠中ER应激诱导的足细胞凋亡有关。 方法 以5和10 mg·kg -1 ·d -1 的AS-IV处理糖尿病大鼠，持续12周。蛋白尿检查，苏木精＆＃38;进行曙红染色和TUNEL分析。免疫组化，免疫印迹和实时荧光定量PCR检测肾上腺皮质激素GRP78和ER相关凋亡蛋白的表达。 结果 用AS-IV改善糖尿病大鼠的蛋白尿和肾脏组织病理学治疗。糖尿病大鼠的足细胞凋亡以及肾脏中的磷酸化PERK和eIF2α都有显着增加，这些被AS-IV治疗所减弱。此外，发现糖尿病大鼠具有增加的GRP78和ER相关凋亡蛋白，例如ATF4，CHOP和TRB3的蛋白和mRNA表达，它们也被AS-IV处理减弱。在糖尿病大鼠中检测到Bax表达增加和Bcl-2表达减少，这些改变通过AS-IV处理得以部分恢复。 结论 AS-IV对内质网应激诱导的足细胞凋亡的保护作用与抑制PERK-ATF4-CHOP途径有关。 AS-IV下调PERK-ATF4-CHOP途径可能是治疗DN的新策略。

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