Xiu Zhi-Ming, Wang Li-Ping, Fu Jun, Xu Jia, Liu Li
Center for Pharmacological Evaluation and Research, Shanghai Institute of Pharmaceutical Industry, 1111 Zhongshan North Road, Shanghai 200437, PR China; Changchun BC&HC Pharmaceutical Technology CO., Ltd, 668 Chuangxin road, Changchun 130012, PR China.
School of Life Science, Jilin University, Changchun 130012, PR China.
Bioorg Med Chem Lett. 2017 Sep 15;27(18):4482-4487. doi: 10.1016/j.bmcl.2017.08.002. Epub 2017 Aug 2.
Diabetic nephropathy (DN) is the most common and serious complication in diabetes mellitus, but the efficacy of available strategies for preventing this disorder remains poor. The aim of this study was to investigate the possible beneficial effects of 1-acetyl-5-phenyl-1H-pyrrol-3-ylacetate (APPA), an aldose reductase inhibitor, on DN. In the present study, a model of rat glomerular mesangial cells (HBZY-1) damaged by high glucose was used to confirm the protective effects of APPA in vitro. Then, a rat model of streptozotocin-induced diabetes was used to assess the effects of APPA in vivo. APPA increased viability and reduced apoptosis in HBZY-1 cells. In vivo, APPA improved the signs of DN as determined by measurements of blood glucose, urinary microalbumin, serum total antioxidant capacity, serum catalase activity, serum glutathione levels, and serum total superoxide dismutase activity. Hematoxylin and eosin staining of kidney tissue confirmed the protective effect. Moreover, APPA reduced the levels of transforming growth factor-β1, collagen IV, and laminin in HBZY-1cells incubated in high glucose, and in serum in DN rats. In summary, APPA can effectively prevent apoptosis and the symptoms of streptozotocin-induced diabetes by inhibiting the polyol pathway in rats. This suggests that APPA could be a potential drug in treating DN.
糖尿病肾病（DN）是糖尿病最常见且最严重的并发症，但现有预防该疾病策略的疗效仍然欠佳。本研究旨在探讨醛糖还原酶抑制剂1-乙酰基-5-苯基-1H-吡咯-3-基乙酸酯（APPA）对糖尿病肾病可能的有益作用。在本研究中，采用高糖损伤的大鼠肾小球系膜细胞（HBZY-1）模型在体外证实APPA的保护作用。然后，使用链脲佐菌素诱导的糖尿病大鼠模型评估APPA在体内的作用。APPA可提高HBZY-1细胞的活力并减少其凋亡。在体内，通过测量血糖、尿微量白蛋白、血清总抗氧化能力、血清过氧化氢酶活性、血清谷胱甘肽水平和血清总超氧化物歧化酶活性，APPA改善了糖尿病肾病的症状。肾组织苏木精-伊红染色证实了其保护作用。此外，APPA降低了在高糖环境中培养的HBZY-1细胞以及糖尿病肾病大鼠血清中转化生长因子-β1、IV型胶原和层粘连蛋白的水平。总之，APPA可通过抑制大鼠的多元醇途径有效预防链脲佐菌素诱导的糖尿病的细胞凋亡和症状。这表明APPA可能是一种治疗糖尿病肾病的潜在药物。
