探讨长链非编码RNA（lncRNA） Rpph1促进糖尿病肾病（diabetes nephropathy, DN）足细胞损伤，是否与腺苷酸激活蛋白激酶（AMP-activated protein kinase, AMPK）／核因子E2相关因子2（Nrf2）信号通路以及细胞焦亡和凋亡有关。体外培养人肾小球足细胞（Human glomerular podocytes, HGPC）随机分为对照组、模型组、lncRNA Rpph1过表达组、低表达组和空载体组，5 mmol/L的D-葡萄糖孵育HGPC为对照组，其他三组采用30 mmol/L的D-葡萄糖孵育细胞建立DN模型。脂质体转染法将携带lncRNA Rpph1过表达、低表达与空载体的稳定质粒与HGPC共孵育。qRT-PCR检测lncRNA Rpph1表达，Western blot检测p-AMPK/AMPK和Nrf2蛋白，以及细胞焦亡相关蛋白包括Nod样受体热蛋白结构域相关蛋白3（NLRP3）、胱天蛋白酶-1（caspase-1）和GSDMD-N的表达量，MTT法检测细胞存活率，流式细胞术检测凋亡率。与对照组相比，模型组lncRNA Rpph1表达量显著增加（P < 0.05）。模型组p-AMPK/AMPK、Nrf2、NLRP3、caspase-1和GSDMD-N蛋白表达量显著增加（P < 0.05）。模型组细胞存活率显著减少，凋亡率增加（P < 0.05）。与模型组和空载体组相比，lncRNA Rpph1过表达组lncRNA Rpph1、p-AMPK/AMPK、Nrf2、NLRP3、caspase-1和GSDMD-N蛋白表达量显著增加，细胞存活率显著减少，凋亡率增加（P < 0.05）；lncRNA Rpph1低表达组lncRNA Rpph1、p-AMPK/AMPK、Nrf2、NLRP3、caspase-1和GSDMD-N蛋白表达量显著下降，细胞存活率显著增多，凋亡率下降（P < 0.05）。DN中lncRNA Rpph1高表达可以促进足细胞损伤，可能通过AMPK/Nrf2信号通路激活细胞焦亡和凋亡有关。

To investigate the mechanism of lncRNA (long chain non coding RNA) Rpph1 activating cytopyrosis through AMP-AMPK(activated protein kinase)/Nrf2(nuclear factor E2 related factor 2) signaling pathway, then to promote podocyte injury in DN(diabetes nephropathy). HGPC(Human glomerular podocytes) were cultured in vitro and randomly divided into control group, model group, lncRNA Rpph1 over-expression group, low-expression group, and empty vector group. HGPC were incubated with 5 mmol/L D-glucose as control group, while the other three groups were incubated with 30 mmol/L D-glucose to establish DN model. Liposome transfection method was used to co-incubate stable plasmids carrying Rpph1 over-expression, low-expression, and empty vector with HGPC. qRT-PCR was used to detect lncRNA Rpph1 expression, Western blot was used to detect p-AMPK/AMPK and Nrf2 proteins, as well as the expression levels of cytopyrosis related proteins including NLRP3 (Nod like receptor thermal domain associated protein 3), caspase-1, and GSDMD-N. MTT assay was used to detect cell survival rate. Flow cytometry was used to detecte apoptosis rate. Compared with control group, the expression level of lncRNA Rpph1 in model group significantly increased (P < 0.05). The expression levels of p-AMPK/AMPK, Nrf2, NLRP3, caspase-1, and GSDMD-N proteins significantly increased in model group (P <0.05). The survival rate of model group cells significantly reduced, while apoptosis rate increased in model group (P < 0.5). Compared with model group and empty vector group, lncRNA Rpph1, p-AMPK/AMPK, Nrf2, NLRP3, caspase-1, and GSDMD-N proteins in lncRNA Rpph1 over-expression group significantly increased, and cell survival rate significantly reduced, apoptosis rate increased (P < 0.05). The expression levels of lncRNA Rpph1, p-AMPK/AMPK, Nrf2, NLRP3, caspase-1, and GSDMD-N proteins significantly decreased in lncRNA Rpph1 low-expression group, and cell survival rate significantly increased, apoptosis rate reduced(P < 0.05). In all, High expression of lncRNA Rpph1 in DN may activate cytopyrosis and promote podocyte injury by AMPK/Nrf2 signaling pathway.