Treatment of db/db diabetic mice with triptolide: a novel therapy for diabetic nephropathy
Treatment of db/db diabetic mice with triptolide: a novel therapy for diabetic nephropathy
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DOI：
10.1093/ndt/gfq245
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发表时间：
2010-11-01
影响因子：
6.1
通讯作者：
Liu, Zhihong
中科院分区：
文献类型：
--
作者：
Gao, Qing;Shen, Wenwen;Liu, Zhihong
背景资料。目前对糖尿病肾病进展的研究提出了许多重要的因素：代谢紊乱、血流动力学异常、慢性炎症、氧化应激、先天性免疫系统激活和足细胞病变。雷公藤甲素是从中药雷公藤中提纯的活性二萜类化合物，具有抗炎、抗氧化、免疫抑制和足细胞保护作用。在此，我们观察了雷公藤甲素对db/db糖尿病小鼠糖尿病肾病的治疗作用，并探讨了其可能的机制。糖尿病肾病DB/db小鼠给予雷公藤甲素或缬沙坦治疗。分别于治疗4、8、12周后检测24 h尿白蛋白、血生化指标及体重。定量测定肾小球面积、肾小球体积/包膜体积比、足细胞变化及炎症和氧化应激标志物来评价肾脏损害。雷公藤甲素治疗后，db/db糖尿病小鼠的蛋白尿明显减轻，肾小球肥大和足细胞损伤减轻。此外，肾脏的炎症和氧化应激也有所减轻，伴随着高脂血症和肥胖症的改善。雷公藤甲素的疗效随着雷公藤甲素治疗时间的延长而增加，且高剂量组疗效优于低剂量组。雷公藤甲素抗肾小球肥大的作用与valsartan相似，但对肾脏炎症和氧化应激的影响比valsartan更明显。雷公藤甲素可显著减轻db/db糖尿病小鼠的蛋白尿和伴有血脂异常及肥胖的肾脏病变。它是一种对防止糖尿病肾病进展起到全面保护作用的新药。
Background. Current research on the progression of diabetic nephropathy (DN) suggests many important factors; metabolic disturbance, haemodynamic abnormity, chronic inflammation, oxidative stress, innate immune system activation and podocyte lesion. Triptolide, which is active diterpene purified from the traditional Chinese medicine Tripterygium wilfordii Hook F (TwHF), has anti-inflammatory, anti-oxidative, immunosuppressive and podocyte-protective effects. Herein, we investigated the therapeutic effects of triptolide on DN in db/db diabetic mice and studied the potential mechanisms.Methods. db/db mice with DN were administrated with triptolide or valsartan. After 4, 8 and 12 weeks of treatment, 24-h urine albumin level, blood biochemical parameters and body weight were measured. Glomerulus area, glomerulus volume to Bowman's capsule volume ratio, podocyte changes and inflammatory and oxidative stress markers were quantitatively determined to evaluate renal lesions.Results. The albuminuria in db/db diabetic mice was markedly attenuated after triptolide treatment, accompanied with alleviated glomerular hypertrophy and podocyte injury. In addition, the inflammation and oxidative stress in the kidneys were also attenuated, accompanied with improved hyperlipidaemia and obesity. The efficacy increased with the prolonging of triptolide treatment, and the efficacy in high-dose triptolide group was superior to that in the low-dose group. The effect of triptolide on glomerular hypertrophy was similar to valsartan, but the effects of triptolide on renal inflammation and oxidative stress were more profound than those of valsartan.Conclusions. Triptolide can dramatically attenuate albuminuria and renal lesion accompanied with dyslipidaemia and obesity in db/db diabetic mice. It is a new drug that exerts comprehensive protective effects on preventing DN progression.