Jiangtang decoction ameliorate diabetic nephropathy through the regulation of PI3K/Akt-mediated NF-κB pathways in KK-Ay mice.
Jiangtang decoction ameliorate diabetic nephropathy through the regulation of PI3K/Akt-mediated NF-κB pathways in KK-Ay mice.
复制标题
降糖汤通过调节 PI3K/Akt 介导的 NF-κ B 通路改善 KK-Ay 小鼠糖尿病肾病
DOI：
10.1186/s13020-017-0134-0
复制
发表时间：
2017
期刊：
影响因子：
4.9
通讯作者：
Wang XM
中科院分区：
文献类型：
--
作者：
Hong JN;Li WW;Wang LL;Guo H;Jiang Y;Gao YJ;Tu PF;Wang XM
降糖汤是由地锦草、丹参、黄芪、当归、黄连组成的中成药。几十年来，它也被用于临床有效地治疗糖尿病肾病（DN）;然而，相关的机制仍然未知。因此，本研究旨在检查JTD在DN中的保护作用并阐明潜在的分子机制。使用KK-Ay小鼠的糖尿病模型每天接受JTD给药，持续12周。每4周测量体重、血糖、甘油三酯（TG）、总胆固醇（TC）、尿素氮（UN）、肌酐（Cr）和微量白蛋白/尿肌酐（MA/UCREA）。此外，在处死当天，采集血液、尿液和肾脏，根据一般参数评估肾功能。病理染色观察JTD对肾脏的保护作用。此外，还评估了炎性细胞因子（肿瘤坏死因子-α [TNF-α]、白细胞介素[IL]-6和细胞间粘附分子[ICAM]-1）、胰岛素受体底物[IRS]-1、晚期糖基化终末产物[AGEs]和糖基化终末产物受体[EGA]的水平。最后，进一步分析磷脂酰肌醇3-激酶（PI 3 K）/蛋白激酶B（Akt）信号通路及核因子-κB（NF-κB）的参与。二甲双胍和JTD给药12周后，小鼠的葡萄糖和脂质代谢功能障碍显著改善，肾组织形态学变化减少，尿白蛋白排泄减少，肌酐清除率正常化。JTD处理还减少AGEs和E2的积累，上调IRS-1，并增加PI 3 K（p85）和Akt的磷酸化，表明参与了PI 3 K/Akt信号通路的激活。此外，JTD给药降低了肾脏炎症介质的升高水平，并降低了NF-κB p65的磷酸化。这些结果表明JTD可能通过PI 3 K/Akt和NF-κB信号通路减轻DN的炎症反应。本文的在线版本（doi：10.1186/s13020-017-0134-0）包含补充材料，可供授权用户使用。
Jiangtang decoction (JTD) is a China patented drug which contains Euphorbia humifusa Willd, Salvia miltiorrhiza Bunge, Astragalus mongholicus Bunge, Anemarrhena asphodeloides Bunge, and Coptis chinensis Franch. For decades, it has also been used clinically to treat diabetic nephropathy (DN) effectively; however, the associated mechanisms remain unknown. Thus, the present study aimed to examine the protective efficacy of JTD in DN and elucidate the underlying molecular mechanisms. A diabetic model using KK-Ay mice received a daily administration of JTD for 12 weeks. Body weight, blood glucose, triglycerides (TGs), total cholesterol (TC), urea nitrogen (UN), creatinine (Cr), and microalbumin/urine creatinine (MA/UCREA) was measured every 4 weeks. Furthermore, on the day of the sacrifice, blood, urine, and kidneys were collected to assess renal function according to general parameters. Pathological staining was performed to evaluate the protective renal effect of JTD. In addition, the levels of inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin [IL]-6 and intercellular adhesion molecule [ICAM]-1), insulin receptor substrate [IRS]-1, advanced glycation end products [AGEs], and receptor of glycation end products [RAGE] were assessed. Finally, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and involvement of nuclear factor-κB (NF-κB) was further analyzed. After 12 weeks of metformin and JTD administration, the mice exhibited a significant amelioration in glucose and lipid metabolism dysfunction, reduced morphological changes in the renal tissue, decreased urinary albumin excretion, and normalized creatinine clearance. JTD treatment also reduced the accumulation of AGEs and RAGE, up-regulated IRS-1, and increased the phosphorylation of both PI3K (p85) and Akt, indicating that the activation of the PI3K/Akt signaling pathway was involved. Additionally, JTD administration reduced the elevated levels of renal inflammatory mediators and decreased the phosphorylation of NF-κB p65. These results demonstrate that JTD might reduce inflammation in DN through the PI3K/Akt and NF-κB signaling pathways. The online version of this article (doi:10.1186/s13020-017-0134-0) contains supplementary material, which is available to authorized users.