Lin Ya-Jun, Zhen Yong-Zhan, Wei Jing-Bo, Wei Jie, Dai Jing, Gao Jun-Ling, Li Kai-Ji, Hu Gang
The Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China.
Hebei Key Laboratory for Chronic Diseases, Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China.
Exp Ther Med. 2017 Dec;14(6):5801-5808. doi: 10.3892/etm.2017.5283. Epub 2017 Oct 11.
The purpose of the present study was to assess the protective effects of rhein lysinate (RHL) in a KK/HlJ mouse model of diabetic nephropathy (DN) and to explore its mechanism of action. A total of 4 groups were established: C57BL/J control, the KK/HlJ model and 25 and 50 mg/kg/day RHL-treated KK/HlJ groups. The KK/HlJ mouse model of DN was established by streptozotocin injection, followed by maintenance on a specific diet. The albumin-to-creatinine ratio (ACR) was determined at 5 weeks and at 16 weeks, the kidneys were harvested, and morphological examination and immunohistochemical analysis were performed. The levels of malondialdehyde (MDA), as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activities in the kidneys were measured using appropriate assay kits. The expression of inflammatory factors and associated proteins was analyzed using western blot analysis. At 5 weeks, the levels of ACR in KK/HlJ mice were increased, which was inhibited by treatment with RHL. Treatment with RHL (50 mg/kg/day) decreased the body weight of KK/HlJ mice. Compared with the C57BL/J control, the KK/HlJ model mice had a significantly lower activity of SOD and GSH-px in the kidneys, but had significantly higher levels of MDA. Treatment of KK/HlJ mice with RHL significantly increased the activities SOD and GSH-px, and reduced the MAD level in the kidneys. Renal tubular epithelial cell edema was observed in KK/HlJ mice but not in C57BL/J mice. RHL decreased the incidence of renal tubular epithelial cell edema and significantly decreased the expression of TNF-α and IL-6 as well as the expression and phosphorylation of NF-κB in the kidneys. Therefore, DN is associated with the expression of inflammatory factors, renal tubular epithelial cell edema and renal dysfunction in KK/HlJ mice. RHL improves renal function by decreasing kidney inflammation.
本研究的目的是评估赖氨大黄素（RHL）在糖尿病肾病（DN）的KK/HlJ小鼠模型中的保护作用，并探讨其作用机制。共设立了4组：C57BL/J对照组、KK/HlJ模型组以及25和50mg/kg/天RHL处理的KK/HlJ组。通过链脲佐菌素注射建立DN的KK/HlJ小鼠模型，随后给予特定饮食维持。在第5周和第16周测定白蛋白与肌酐比值（ACR），采集肾脏，进行形态学检查和免疫组化分析。使用合适的检测试剂盒测量肾脏中丙二醛（MDA）水平以及超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-px）活性。使用蛋白质印迹分析来分析炎症因子和相关蛋白的表达。在第5周时，KK/HlJ小鼠的ACR水平升高，而RHL处理可抑制该升高。RHL（50mg/kg/天）处理降低了KK/HlJ小鼠的体重。与C57BL/J对照组相比，KK/HlJ模型小鼠肾脏中的SOD和GSH-px活性显著降低，但MDA水平显著升高。用RHL处理KK/HlJ小鼠可显著提高SOD和GSH-px活性，并降低肾脏中的MAD水平。在KK/HlJ小鼠中观察到肾小管上皮细胞水肿，而在C57BL/J小鼠中未观察到。RHL降低了肾小管上皮细胞水肿的发生率，并显著降低了肾脏中TNF-α和IL-6的表达以及NF-κB的表达和磷酸化。因此，在KK/HlJ小鼠中，DN与炎症因子表达、肾小管上皮细胞水肿和肾功能障碍有关。RHL通过减轻肾脏炎症来改善肾功能。
