摘要
目的:探索抑制核转录因子(NF)-κB信号通路对顺铂致肺癌大鼠肾损伤的保护作用及其分子机制研究。方法:将50只大鼠随机分为5组:正常对照组、肺癌组(Lewis细胞)、顺铂组(Lewis细胞+腹腔注射顺铂溶液5 mg·kg^-1)、吡咯烷二硫代氨基甲酸盐(PDTC)组(Lewis细胞+腹腔注射PDTC 25 mg·kg^-1)、PDTC+顺铂组(Lewis细胞+腹腔注射顺铂和PDTC),每组10只。末次给药后,生化分析仪检测血清肌酐(SCr)、尿素氮(BUN)、胱抑素C(Cys C)、尿液肾损伤分子-1(Kim-1)水平,ELISA法测定肾组织中超氧化物歧化酶(SOD)和丙二醛(MDA)水平,RT-PCR检测肾组织肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6水平,Western Blotting检测核因子2相关因子2(Nrf2)、血红素氧合酶-1(HO-1)、NF-κB p65、p-IκBα/IκBα的表达,HE染色检测肾组织损伤。结果:与肺癌组相比,顺铂组大鼠血SCr、BUN、Cys C、尿Kim-1水平及肾组织MDA、TNF-α、IL-1β、IL-6 mRNA、Nrf2、HO-1、NF-κB p65和p-IκBα/IκBα的表达明显升高(P<0.05),肾组织SOD活性和GSH-Px活性明显降低(P<0.05);与顺铂组相比,PDTC+顺铂组大鼠血SCr、BUN、Cys C、尿Kim-1水平及肾组织MDA、TNF-α、IL-1β、IL-6 mRNA、NF-κB p65和p-IκBα/IκBα的表达明显明显降低(P<0.05),肾组织SOD、GSH-Px、Nrf2和HO-1的表达明显升高(P<0.05)。结论:抑制NF-κB信号通路可以降低炎症因子水平,还可以激活Nrf2的表达,降低氧化应激水平,保护顺铂致肺癌大鼠的肾组织损伤。
Objective:To explore the protective effect of inhibiting nuclear transcription factor-κB(NF-κB)signaling pathway on cisplatin-induced renal injury in lung cancer rats and its molecular mechanism.Methods:Totally 50 rats were randomly divided into 5 groups:the normal control group,lung cancer group(Lewis cells),cisplatin group(Lewis cells and intraperitoneal injection of 5 mg·kg^-1 cisplatin solution),pyrrolidine dithiocarbamate(PDTC)group(Lewis cells and intraperitoneal injection of 25 mg·kg^-1 PDTC)and PDTC+cisplatin group(Lewis cells,intraperitoneal injection of cisplatin and PDTC)with 10 cases in each group.After the last administration,the levels of serum creatinine(SCr),blood urea nitrogen(BUN),cystatin C(Cys C)and kidney damage molecule-1(Kim-1)were detected by a biochemical analyzer.The levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in renal tissue were detected by ELISA.RT-PCR was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1βand IL-6.The expressions of nuclear transcription factor E2 related factor 2(Nrf2),heme oxygenase-1(HO-1),NF-κB p65 and p-IκBα/IκBαwere detected by Western Blotting.HE staining was applied to detect renal tissue damage.Results:Compared with those in lung cancer group,the levels of SCr,BUN,Cys C and urinary Kim-1 in blood,the levels of MDA,TNF-α,IL-1βand IL-6 mRNA,and the expressions of Nrf2,HO-1,NF-κB p65 and p-IκBα/IκBαin renal tissue in cisplatin group were significantly increased(P<0.05),while the activities of SOD and glutathione peroxidase(GSH-Px)in renal tissue were significantly decreased(P<0.05).Compared with those in cisplatin group,the levels of SCr,BUN,Cys C and urinary Kim-1 in blood,the levels of MDA,TNF-α,IL-1βand IL-6 mRNA,and the expressions of NF-κB p65 and p-IκBα/IκBαin renal tissue in PDTC+cisplatin group were significantly decreased(P<0.05),while the activities of SOD,GSH-Px,Nrf2 and HO-1 in renal tissue were significantly increased(P<0.05).Conclusion:Inhibiting NF-κB signaling pathway can re
作者
张雷
苗晓云
李菁
韩国达
乔梁
朱昆奥
Zhang Lei;Miao Xiaoyun;Li Jing;Han Guoda;Qiao Liang;Zhu Kun'ao(Department of Laboratory,Cangzhou Central Hospital,Hebei Cangzhou 061001,China;Department of Critical Care Medicine,Cangzhou Central Hospital,Hebei Cangzhou 061001,China;Department of Ophthalmology,Cangzhou Central Hospital,Hebei Cangzhou 061001,China;Department of Oncology,Cangzhou Central Hospital,Hebei Cangzhou 061001,China)
出处
《中国药师》
CAS
2020年第7期1274-1279,共6页
China Pharmacist
基金
河北省沧州市科学技术局项目(编号:183302086)。
关键词
核转录因子-κB信号通路
顺铂
肺癌
肾损伤
Nuclear transcription factor-κB signaling pathway
Cisplatin
Lung cancer
Renal injury
