和厚朴酚调控Klotho改善顺铂诱导小鼠急性肾损伤的研究  

Honokiol ameliorates cisplatin-induced acute kidney injury in mice by regulating Klotho

作　　者：殷思敏 王思怡 黄东升 江嘉颖 周玖瑶[1] 周园[1] YIN Si-min;WANG Si-yi;HUANG Dong-sheng;JIANG Jia-ying;ZHOU Jiu-yao;ZHOU Yuan(School of Chinese Medicine,Guangzhou University of Chinese Medicine,Guangzhou 510000,Guangdong Province,China)

机构地区：[1]广州中医药大学中药学院,广东广州510000

出　　处：《中国临床药理学杂志》2023年第19期2798-2802,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的探讨和厚朴酚对顺铂诱导小鼠急性肾损伤的影响及机制。方法将40只Balb/C小鼠随机分为对照组(30%PEG400)、模型组(20 mg·kg^(-1)顺铂+30%PEG400)、低、中、高剂量实验组(10、20、40 mg·kg^(-1)和厚朴酚腹腔注射),每组8只。各组均分别连续5 d腹腔注射相应试剂,每日1次。给药第3天时,除对照组予以0.9%NaCl外,其余各组均单次腹腔注射顺铂20 mg·kg^(-1)建立肾毒性小鼠模型。以酶联免疫检测法测定血清肌酸酐(SCr)、尿素氮(BUN),用肾组织匀浆法测定丙二醛(MDA)水平;用蛋白质印迹法检测Klotho、B-细胞淋巴瘤2相关X蛋白(Bax)、B-细胞淋巴瘤因子2蛋白(Bcl-2)、线粒体超氧化物歧化酶蛋白2(SOD2)的表达水平。结果对照组、模型组和低、中、高剂量实验组的尿素氮分别为(6.61±0.56)、(19.62±4.74)、(13.59±3.07)、(10.00±5.24)和(9.59±3.13)mmol·L^(-1),血清肌酸酐分别为(14.08±2.74)、(46.17±11.65)、(27.21±3.99)、(18.87±5.33)和(20.00±2.10)μmol·L^(-1),MDA分别为(2.56±0.26)、(2.90±0.18)、(2.37±0.12)、(2.24±0.26)和(1.68±0.50)nmol·mg-1,Klotho蛋白相对表达水平分别为1.07±0.13、0.70±0.11、0.91±0.08、1.09±0.11和1.22±0.06,Bax/Bcl-2比值分别为1.05±0.17、1.84±0.06、1.23±0.20、0.96±0.12和0.79±0.23,SOD2蛋白相对表达水平分别为1.15±0.09、0.59±0.12、0.83±0.22、1.01±0.16和1.15±0.19。模型组的上述指标与空白组比较,差异均有统计学意义(P<0.01,P<0.05);中、高剂量实验组的上述指标与模型组比较,差异均有统计学意义(P<0.01,P<0.05)。结论和厚朴酚可上调肾组织Klotho表达,抑制凋亡、改善氧化应激,减轻顺铂诱导的小鼠急性肾损伤。Objective To investigate the effect and mechanism of honokiol on cisplatin-induced acute kidney injury in mice.Methods Forty Balb/C mice were randomly divided into control group(30%PEG400),model group(20 mg·kg^(-1)cisplatin+30%PEG400),and experimental-L,-M,-H groups(10,20,40 mg·kg^(-1)honokiol intraperitoneal injection),with 8 mice in each group.Each group was intraperitoneally injected with the corresponding reagents for 5consecutive days,once a day.On the third day of administration,except for 0.9%Na Cl in the control group,a single intraperitoneal injection of cisplatin(20 mg·kg^(-1))was performed to establish the model of nephrotoxicity.Serum creatinine(SCr)and blood urea nitrogen(BUN)were measured by enzyme-linked immunosorbent assay;malondialdehyde(MDA)level was measured by renal tissue homogenate method;the levels of Klotho,B-cell lymphoma-2 associated X protein(Bax),B-cell lymphoma-2(Bcl-2)and mitochondrial superoxide dismutase 2(SOD2)were detected by Western blotting.Results The levels of urea nitrogen in control group,model group and experimental-L,-M,-H groups were(6.61±0.56),(19.62±4.74),(13.59±3.07),(10.00±5.24)and(9.59±3.13)mmol·L^(-1),respectively;the serum creatinine levels were(14.08±2.74),(46.17±11.65),(27.21±3.99),(18.87±5.33)and(20.00±2.10)μmol·L^(-1),respectively;the MDA were(2.56±0.26),(2.90±0.18),(2.37±0.12),(2.24±0.26)and(1.68±0.50)nmol·mg^(-1),respectively;the relative expression levels of Klotho protein were 1.07±0.13,0.70±0.11,0.91±0.08,1.09±0.11 and 1.22±0.06,respectively;the ratios of Bax/Bcl-2 protein were1.05±0.17,1.84±0.06,1.23±0.20,0.96±0.12 and 0.79±0.23,respectively;the relative expression levels of SOD2 protein were 1.15±0.09,0.59±0.12,0.83±0.22,1.01±0.16 and 1.15±0.19,respectively.There were significant differences in the above indicators between the model group and the blank group(P<0.01,P<0.05);there were significant differences in the above indicators between the experimental-M,-H groups and the model group(P<0.01,P<0.05).Conclusion Hono

关 键 词：和厚朴酚 顺铂 急性肾损伤 KLOTHO基因 

分 类 号：R28[医药卫生—中药学]