机构地区:[1]上海交通大学医学院附属第九人民医院肾脏内科,上海200011 [2]上海交通大学医学院附属第九人民医院中医科,上海200011
出 处:《西部医学》2022年第10期1414-1419,共6页Medical Journal of West China
基 金:上海交通大学“交大之星”计划医工交叉研究基金(YG2021ZD15)。
摘 要:目的基于核因子NF-E2相关因子(Nrf2)/抗氧化物反应元件(ARE)信号通路探究人参皂苷Rg3对高糖诱导人肾小球系膜细胞(HMC)纤维化及生物活性作用机制。方法将人肾小球系膜细胞分为NC组、HG组、Rg3A组、Rg3B组、Rg3C组5组。检测细胞生物活性;荧光探针DCFH-DA法检测细胞中ROS含量;蛋白质印迹检测细胞中Nrf2、HO-1蛋白及TGF-β、Ⅳ-C、FN蛋白表达。结果与NC组相比,HG组细胞增殖活性及侵袭能力均显著增加(P<0.05);与HG组相比,Rg3A组、Rg3B组、Rg3C组细胞增殖活性及侵袭能力均显著降低(P<0.05);Rg3C组细胞增殖活性及侵袭能力显著低于Rg3A组、Rg3B组(P<0.05)。与NC组相比,HG组细胞凋亡率显著降低,G1期增加(P<0.05);与HG组相比,Rg3A组、Rg3B组、Rg3C组细胞凋亡率均显著增加,G1期均显著降低,Rg3C组细胞G1期<Rg3B组<Rg3A组(P<0.05),呈递增趋势(P<0.05),且Rg3C组细胞凋亡率和细胞周期变化最为显著(P<0.05)。与NC组相比,GH组细胞中ROS含量显著增加(P<0.05);与GH组相比,Rg3A组、Rg3B组、Rg3C组细胞中ROS含量均显著降低(P<0.05)。与NC组相比,GH组细胞中NNrf2和HO-1蛋白表达均显著降低(P<0.05);与GH组相比,Rg3A组、Rg3B组、Rg3C组细胞中Nrf2、HO-1蛋白表达均显著增加,且Rg3C组细胞中蛋白表达增加最显著(P<0.05)。与NC组相比,GH组细胞中TGF-β、Ⅳ-C、FN明显增加(P<0.05);与GH组相比,Rg3A组、Rg3B组、Rg3C组细胞中TGF-β、Ⅳ-C、FN表达均显著降低,且Rg3C组低于Rg3B组低于Rg3A组(P<0.05)。结论人参皂苷Rg3可抑制高糖诱导的HMC细胞增殖、侵袭,促进HMC细胞凋亡,通过对细胞内Nrf2/ARE信号通路相关蛋白的调控加强系膜细胞的抗氧化能力。Objective To explore the mechanism of ginsenoside Rg3 on the fibrosis and biological activity of HMC cells induced by high glucose based on Nrf2/ARE signaling pathway.Methods Human mesangial cells were divided into 5 groups:NC group,HG group,Rg3 A group,Rg3 Bgroup and Rg3 C group.Cell proliferation,invasion,apoptosis and cell cycle were detected.Fluorescence probe DCFH-DA method was used to detect ROS content in cells.The expressions of Nrf2,HO-1,TGF-β,IV-C and FN were detected by Western blot.Results Compared with NC group,the proliferation activity and invasion ability of HG group were significantly increased(P<0.05).Compared with HG group,the proliferation activity and invasion ability of Rg3 A,Rg3 B and Rg3 C groups were significantly decreased(P<0.05).The proliferation activity and invasion ability of Rg3 C group were significantly lower than those of Rg3 A group and Rg3 B group(P<0.05).Compared with NC group,the apoptosis rate of HG group was significantly decreased,and G1 phase was increased(P<0.05).Compared with HG group,the apoptosis rate of Rg3 A group,Rg3 B group and Rg3 C group was significantly increased,and the G1 phase was significantly decreased with an increasing trend(P<0.05),and the apoptosis rate and cell cycle change of Rg3 C group were the most significant(P<0.05).Compared with NC group,ROS content in GH group was significantly increased(P<0.05).Compared with GH group,ROS content in Rg3 A,Rg3 B and Rg3 C groups was significantly decreased(P<0.05).Compared with NC group,the protein expressions of NNrf2 and HO-1 in GH group were significantly decreased(P<0.05).Compared with GH group,the protein expressions of Nrf2 and HO-1 in Rg3 A group,Rg3 B group and Rg3 C group were significantly increased,and the protein expression in Rg3 C group was most significantly increased(P<0.05).Compared with NC group,TGF-β,ⅳ-c and FN in GH group were significantly increased(P<0.05).Compared with GH group,the expressions of TGF-β,IV-c and FN in Rg3 A,Rg3 B and Rg3 C groups were significantly decreased,and the
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