Kidney protection effects of dihydroquercetin on diabetic nephropathy through suppressing ROS and NLRP3 inflammasome
Kidney protection effects of dihydroquercetin on diabetic nephropathy through suppressing ROS and NLRP3 inflammasome
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二氢槲皮素通过抑制ROS和NLRP3炎症小体对糖尿病肾病的肾脏保护作用
DOI：
10.1016/j.phymed.2018.01.026
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发表时间：
2018-03-01
期刊：
影响因子：
7.9
通讯作者：
Mei Xiaobin
中科院分区：
文献类型：
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作者：
Ding Tao;Wang Shaofei;Mei Xiaobin
背景资料：糖尿病肾病（diabetic nephropathy，DN）是终末期肾病的主要病因，也是心血管疾病的独立危险因素，因此迫切需要新的治疗药物。二氢槲皮素（Dihydroquercetin，DHQ）是一种重要的天然二氢黄酮，具有显著的抗氧化、抗炎、抗纤维化等作用，但其对糖尿病肾病（DN）的治疗作用尚未见报道。目的：探讨DHQ对高脂饮食/链脲佐菌素（STZ）诱导的DN大鼠肾脏的保护作用，并探讨DHQ对高糖诱导的肾细胞HBZY-1和HK 2的保护作用机制。主要生化指标包括尿微量白蛋白、空腹血糖、血肌酐、总胆固醇、低密度脂蛋白胆固醇。肾组织切片用苏木精-伊红、过碘酸-Schiff和Masson染色。MTT法检测细胞增殖情况。DCFH-DA法和激光扫描共聚焦显微镜检测细胞内活性氧（ROS）的产生。结果：DHQ 100 mg/kg/d可明显减轻高脂饮食/链脲佐菌素诱导的DN大鼠尿微量白蛋白排泄量增加、高血糖及脂代谢紊乱，减轻肾脏组织病理学损害。在体外实验中，DHQ可明显抑制高糖诱导的细胞增殖和ROS的过度产生，并减轻高糖诱导的NLRP 3炎性小体的激活和肾纤维化相关蛋白的表达。结果表明，DHQ具有减轻糖尿病肾病大鼠尿微量白蛋白排泄、高血糖及脂代谢紊乱、减轻肾脏病理损害等肾脏保护作用。抑制ROS和NLRP 3炎性小体可能是其肾脏保护机制之一。
Background: Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is acknowledged as an independent risk factor for cardiovascular disease, which underlines the urgent need for new medications to DN. Dihydroquercetin (DHQ), an important natural dihydroflavone, exerts significant antioxidant, anti-inflammatory, and antifibrotic properties, but its effects on DN have not been investigated yet.Purpose: We aimed to explore the kidney protection effects of DHQ on DN rats induced by high-fat diet/streptozotocin in vivo and the underlying mechanisms of DHQ on renal cells including HBZY-1 and HK2 exposed to high glucose in vitro.Methods: Major biochemical indexes were measured including urine microalbumin, fasting serum glucose, serum levels of creatinine, total cholesterol and low density lipoprotein cholesterol. Renal histologic sections were stained with hematoxylin-eosin, periodic acid-Schiff and Masson. The cell proliferation was assessed by MTT assay. Reactive oxygen species (ROS) generation was detected by DCFH-DA assay and laser scanning confocal microscope. Expression of all proteins was examined by western-blot.Results: In high-fat diet/streptozotocin-induced DN rats, DHQ at the dose of 100 mg/kg/day significantly attenuated the increasing urine microalbumin excretion, hyperglycemia and lipid metabolism disorders, and mitigated renal histopathological lesions. In in vitro studies, DHQ significantly suppressed cell proliferation and the excessive ROS generation, and alleviated the activation of nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and the expression of renal fibrosis-associated proteins in renal cells exposed to high glucose.Conclusion: The results revealed that DHQ possesses kidney protection effects including attenuating urine microalbumin excretion, hyperglycemia and lipid metabolism disorders, and mitigating renal histopathological lesions on DN, and one of the possible renal-protective mechanisms is suppressing ROS and NLRP3 inflammasome.