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Local kallikrein–kinin system is involved in podocyte apoptosis under diabetic conditions

机译:糖尿病条件下局部激肽释放酶-激肽系统参与足细胞凋亡

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摘要

The kallikrein–kinin system (KKS) serves as the physiologic counterbalance to the renin-angiotensin system. This study was conducted to examine the changes in the expression of KKS components in podocytes under diabetic conditions and to elucidate the functional role of bradykinin (BK) in diabetes-associated podocyte apoptosis. Thirty-two rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with BK infusion for 6 weeks. Immortalized mouse podocytes were cultured in media containing 5.6 mmol/l glucose (NG), NG + 10−7 mol/l AII (AII), or 30 mmol/l glucose (HG) with or without 10−8 mol/l BK. Urinary albumin excretion was significantly higher in DM rats, and this increase was ameliorated by BK. Not only kininogen, kallikrein, and BK B1- and B2-receptor expression but also BK levels were significantly decreased in DM glomeruli and in cultured podocytes exposed to HG. The changes in the expressions of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG- and AII-stimulated podocytes were significantly abrogated by BK. The suppressed KSS within podocytes under diabetic condition was associated with podocyte apoptosis, suggesting that BK may be beneficial in preventing podocyte loss in diabetic nephropathy.
机译:激肽释放酶-激肽系统(KKS)作为肾素-血管紧张素系统的生理平衡。进行这项研究以检查糖尿病条件下足细胞中KKS成分表达的变化,并阐明缓激肽(BK)在糖尿病相关足细胞凋亡中的功能。对32只大鼠进行了腹腔注射稀释剂(n = 16,C)或腹膜内注射链脲佐菌素(n = 16,DM),每组中的8只大鼠接受了BK输注治疗6周。在含有5.6 mmol / l葡萄糖(NG),NG + 10 −7 mol / l AII(AII)或30 mmol / l葡萄糖(HG)的培养基中培养永生化的小鼠足细胞 -8 mol / l BK。 DM大鼠的尿白蛋白排泄量显着增加,而BK改善了这种增加。在DM肾小球和暴露于HG的培养足细胞中,不仅激肽原,激肽释放酶和BK B1和B2受体表达显着降低,而且BK水平也显着降低。 BK显着消除了DM肾小球以及HG和AII刺激的足细胞中凋亡相关分子表达的变化和凋亡细胞数量的增加。糖尿病条件下足细胞内KSS的抑制与足细胞凋亡有关,提示BK可能有助于预防糖尿病肾病足细胞的丢失。

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