Preventive effect of Shenkang injection against high glucose-induced senescence of renal tubular cells
Preventive effect of Shenkang injection against high glucose-induced senescence of renal tubular cells
复制标题
肾康注射液对高糖所致肾小管细胞衰老的预防作用
DOI：
10.1007/s11684-017-0586-8
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发表时间：
2019-04-01
影响因子：
8.1
通讯作者：
He, Yani
中科院分区：
文献类型：
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作者：
Fu, Biqiong;Yang, Jie;He, Yani
肾康注射液是由生大黄、黄芪、红花、丹参组成的经典方剂。该治疗方法于1999年获得中国国家食品药品监督管理局批准，用于治疗慢性肾脏疾病，具有良好的疗效和安全性。本研究旨在探讨SKI对高糖诱导的肾小管细胞衰老的保护作用及其机制。原代肾近曲小管上皮细胞在（1）对照培养基中培养（2）甘露醇培养液甘露醇组：葡萄糖5 mmol/L+甘露醇25 mmol/L;高糖组（HG组），高糖组（30 mmol/L），高糖组（40 mmol/L），高糖组（40 mmol/L），高糖组（40 mmol/L），高糖组（40 mmol/L）（200毫克/升），中等在HG培养基中，浓度为100 mg/L或50 mg/L（5）200 mg/L SKI处理72 h（对照+ SKI组）。HG诱导的衰老细胞出现衰老相关的异染色质灶，P16 INK 4和cyclin D1表达上调，衰老相关的β-半乳糖苷酶活性增加，膜诱饵受体2表达增加。SKI治疗以剂量非依赖性方式有效地预防了这些变化。SKI治疗阻止了HG诱导的促衰老分子哺乳动物雷帕霉素和p66 Shc靶点的上调，以及肾小管上皮细胞中抗衰老分子klotho、sirt 1和过氧化物酶体增殖物激活受体-g的下调。SKI可能是治疗糖尿病肾病的一种新的保护措施。
Shenkang injection (SKI) is a classic prescription composed ofRadix Astragali, rhubarb,Astragalus,Safflower, andSalvia. This treatment was approved by the State Food and Drug Administration of China in 1999 for treatment of chronic kidney diseases based on good efficacy and safety. This study aimed to investigate the protective effect of SKI against high glucose (HG)-induced renal tubular cell senescence and its underlying mechanism. Primary renal proximal tubule epithelial cells were cultured in (1) control medium (control group), medium containing 5 mmol/L glucose; (2) mannitol medium (mannitol group), medium containing 5 mmol/L glucose, and 25 mmol/L mannitol; (3) HG medium (HG group) containing 30 mmol/L glucose; (4) SKI treatment at high (200 mg/L), medium (100 mg/L), or low (50 mg/L) concentration in HG medium (HG + SKI group); or (5) 200 mg/L SKI treatment in control medium (control + SKI group) for 72 h. HG-induced senescent cells showed the emergence of senescence associated heterochromatin foci, up-regulation of P16INK4and cyclin D1, increased senescence-associated β-galactosidase activity, and elevated expression of membrane decoy receptor 2. SKI treatment potently prevented these changes in a dose-independent manner. SKI treatment prevented HG-induced up-regulation of pro-senescence molecule mammalian target of rapamycin and p66Shc and down-regulation of anti-senescence molecules klotho, sirt1, and peroxisome proliferator-activated receptor-g in renal tubular epithelial cells. SKI may be a novel strategy for protecting against HG-induced renal tubular cell senescence in treatment of diabetic nephropathy.