An Zeng-Mei, Dong Xing-Gang, Guo Yuan, Zhou Jia-Liang, Qin Tao
Department of Endocrinology, Shanghai Second People's Hospital, Shanghai, 200011, China.
Laboratory Animal Science Center, Fudan University, Shanghai, 200032, China.
J Huazhong Univ Sci Technolog Med Sci. 2015 Jun;35(3):356-361. doi: 10.1007/s11596-015-1437-y. Epub 2015 Jun 14.
Diabetic nephropathy (DN) is a common and serious clinical complication of diabetes and presently there are no effective ways to prevent its occurrence and progression. Recent studies show that pentoxifylline (PTX) can improve renal hemodynamics, reduce urinary protein excretion, and alleviate or delay renal failure in DN patients. In this study, we focused on the anti-oxidative stress effect of PTX on alleviating renal damages of DN using rat models. DN rats were established with injection of streptozotocin. Blood glucose, urinary protein excretion, serum cystatin C, renal biopsy, superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and renal homogenate and renal nitrotyrosine levels were analyzed before and 12 weeks after the treatment of PTX. Before treatment, all the DN rats had elevated blood glucose, increased urinary protein excretion and elevated serum cystatin C. Morphologically, DN rats exhibited renal tissue damages, including swelling and fusions of foot processes of podocytes under electron microscope. Masson staining revealed blue collagen deposition in glomeruli and renal interstitium. With treatment of PTX, symptoms and renal pathological changes of DN rats were alleviated. Furthermore, the MDA levels were increased and the SOD levels were decreased in the serum and kidneys of DN rats, and these changes were reversed by PTX. The expression of nitrotyrosine was up-regulated in DN rat model and down-regulated by PTX, indicating that PTX was able to inhibit oxidative reactions in DN rats. PTX could alleviate renal damage in DN, which may be attributable to its anti-oxidative stress activity.
糖尿病肾病(DN)是糖尿病常见且严重的临床并发症,目前尚无有效的方法来预防其发生和发展。最近的研究表明,己酮可可碱(PTX)可改善肾脏血流动力学,减少尿蛋白排泄,并减轻或延缓DN患者的肾衰竭。在本研究中,我们使用大鼠模型聚焦于PTX减轻DN肾脏损伤的抗氧化应激作用。通过注射链脲佐菌素建立DN大鼠模型。在PTX治疗前及治疗12周后,分析血糖、尿蛋白排泄、血清胱抑素C、肾活检、血清及肾匀浆中的超氧化物歧化酶(SOD)和丙二醛(MDA)以及肾脏硝基酪氨酸水平。治疗前,所有DN大鼠血糖升高、尿蛋白排泄增加且血清胱抑素C升高。形态学上,DN大鼠表现出肾组织损伤,包括电镜下足细胞足突肿胀和融合。Masson染色显示肾小球和肾间质中有蓝色胶原沉积。经PTX治疗后,DN大鼠的症状和肾脏病理变化得到缓解。此外,DN大鼠血清和肾脏中的MDA水平升高,SOD水平降低,而这些变化被PTX逆转。DN大鼠模型中硝基酪氨酸表达上调,而PTX使其下调,表明PTX能够抑制DN大鼠中的氧化反应。PTX可减轻DN中的肾脏损伤,这可能归因于其抗氧化应激活性。