Department of Endocrinology, The Second Hospital of Shijiazhuang, Shijiazhuang, Hebei, China.
Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, China.
Drug Dev Res. 2021 Nov;82(7):990-998. doi: 10.1002/ddr.21801. Epub 2021 Mar 2.
Azithromycin (AZM) has a therapeutic effect on diabetes, but there is no report on whether AZM has a therapeutic effect on diabetic nephropathy (DN) and its specific mechanism. Cell survival was detected by CCK-8. The expression of the inflammatory factors TNF-α, IL-1β, and IL-6 was determined by ELISA. The expression of inflammatory proteins MCP-1, NLPR3, and ASC was detected by western blot. The expression of MDA, LDH, and SOD was detected by the appropriate kit. Apoptosis was detected by flow cytometry and apoptosis-related proteins Bcl-2, Bax, Caspase-3, 6, 9, and Cleaved caspase-3, 6, 9 were detected by western blot. In addition, the expression of STAT1 was detected by western blot. AZM can increase the activity of high glucose-induced podocytes (p < .05). After high glucose induction, the expression of TNF-α, IL-1β, and IL-6 was increased and the expression of MCP-1, NLPR3, and ASC proteins was also increased (p < .001). When AZM was added, the expression of all the above-mentioned proteins was decreased (p < .001). In addition, MDA, LDH, and SOD were increased after high glucose induction, while decreased after AZM treatment (p < .001). AZM can inhibit apoptosis and the expression of Bax and Cleaved caspase-3, 6, 9, and promote the expression of Bcl-2 (p < .001). Furthermore, the expression of STAT1 was increased after high glucose induction, while the expression of STAT1 was decreased after AZM action (p < .01). By adding a STAT1 agonist IFN-γ, the effects of AZM on inflammation, oxidative stress, and apoptosis of high glucose-induced podocytes were inhibited (p < .05). AZM inhibited inflammation, oxidative stress, and apoptosis of high glucose-induced podocytes by inhibiting STAT1 pathway.
阿奇霉素（AZM）对糖尿病具有治疗作用，但尚无 AZM 对糖尿病肾病（DN）是否具有治疗作用及其具体机制的报道。通过 CCK-8 检测细胞存活率。通过 ELISA 测定炎症因子 TNF-α、IL-1β 和 IL-6 的表达。通过 Western blot 检测炎症蛋白 MCP-1、NLPR3 和 ASC 的表达。通过适当的试剂盒检测 MDA、LDH 和 SOD 的表达。通过流式细胞术检测细胞凋亡，通过 Western blot 检测凋亡相关蛋白 Bcl-2、Bax、Caspase-3、6、9 和 Cleaved caspase-3、6、9。此外，通过 Western blot 检测 STAT1 的表达。AZM 可提高高糖诱导的足细胞（p < .05）活性。高糖诱导后，TNF-α、IL-1β 和 IL-6 的表达增加，MCP-1、NLPR3 和 ASC 蛋白的表达也增加（p < .001）。加入 AZM 后，上述所有蛋白的表达均降低（p < .001）。此外，高糖诱导后 MDA、LDH 和 SOD 增加，AZM 处理后减少（p < .001）。AZM 可抑制细胞凋亡，降低 Bax 和 Cleaved caspase-3、6、9 的表达，促进 Bcl-2 的表达（p < .001）。此外，高糖诱导后 STAT1 的表达增加，而 AZM 作用后 STAT1 的表达减少（p < .01）。通过添加 STAT1 激动剂 IFN-γ，抑制了 AZM 对高糖诱导的足细胞炎症、氧化应激和凋亡的作用（p < .05）。AZM 通过抑制 STAT1 通路抑制高糖诱导的足细胞炎症、氧化应激和凋亡。
