Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: An update
Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: An update
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DOI：
10.1016/j.ejphar.2016.08.022
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发表时间：
2016-11-15
影响因子：
5
通讯作者：
Manna, Prasenjit
中科院分区：
文献类型：
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作者：
Bhattacharjee, Niloy;Barma, Sujata;Manna, Prasenjit
糖尿病肾病（DN）是糖尿病的一种慢性并发症，其特征是肾小球肥大、蛋白尿、肾小球滤过减少和肾纤维化导致肾功能丧失。虽然DN的确切原因尚不清楚，但已经提出了几种机制，如高血糖诱导的肾超滤过和肾损伤，ages诱导的氧化应激增加，激活pkc诱导的细胞因子，趋化因子以及不同的炎症和凋亡信号的产生增加。在多种因素中，氧化应激被认为在DN的发生和传播中起主要作用。它触发了与DN相关的几种信号通路，如AGEs、PKC级联、JAK/STAT信号、MAPK、mTOR和SMAD。氧化应激诱导的炎症和凋亡信号的激活是DN发病机制中的两个主要问题。FDA批准的抗多元醇途径的药物治疗药物主要包括抗氧化剂，如a-硫辛酸、维生素E和维生素c。Kremezin和benfotiamine是FDA批准的另一种针对DN的治疗靶点AGEs抑制剂。Ruboxistaurin, telmizartan，雷帕霉素，非诺贝特，阿利克伦和曼尼地平是FDA批准的一些药物治疗药物，通过不同的机制对DN有效。除此之外，一些治疗药物仍在等待FDA的批准，一些国家也很少有未经FDA批准的药物用于治疗DN。尽管市场上有治疗DN的药物，但由于涉及多种机制，很难选择最佳的治疗药物。因此，需要大量的研究来寻找新的治疗药物/策略，以充分的药物治疗DN。(C) 2016 Elsevier B.V.版权所有
Diabetic nephropathy (DN), a chronic complication of diabetes, is charecterized by glomerular hypertrophy, proteinuria, decreased glomerular filtration, and renal fibrosis resulting in the loss of renal function. Although the exact cause of DN remains unclear, several mechanisms have been postulated, such as hyperglycemia-induced renal hyper filtration and renal injury, AGEs-induced increased oxidative stress, activated PKC-induced increased production of cytokines, chemokines, and different inflammatory and apoptotic signals. Among various factors, oxidative stress has been suggested to play a major role underlying the onset and propagation of DN. It triggers several signaling pathways involved in DN, like AGEs, PKC cascade, JAK/STAT signaling, MAPK, mTOR, and SMAD. Oxidative stress-induced activation of both inflammatory and apoptotic signals are two major problems in the pathogenesis of DN. The FDA approved pharmacotherapeutic agents affecting against polyol pathway principally include anti-oxidants, like a-lipoic acid, vitamin E, and vitamin C. Kremezin and benfotiamine are the FDA approved AGEs inhibitors, another therapeutic target against DN. Ruboxistaurin, telmizartan, rapamycin, fenofibrate, aliskiren, and manidipine are some FDA approved pharmacotherapeutics effective against DN via diverse mechanisms. Beside this, some therapeutic agents are still waiting for FDA approval and few drugs without FDA approval are also prescribed in some countries for the management of DN. Despite the medications available in the market to treat DN, the involvement of multiple mechanisms makes it difficult to choose an optimum therapeutic agent. Therefore, much research is required to find out new therapeutic agent/strategies for an adequate pharmacotherapy of DN. (C) 2016 Elsevier B.V. All rights reserved.