目的 研究益髓生血方(YSSX)通过Kelch样环氧氯丙烷相关蛋白1(Keap1)-核因子E2相关因子2(Nrf2)信号通路改善化疗所致小鼠肾损的效果和作用机制.方法 通过腹腔注射40 mg·kg-1卡铂诱导小鼠肾损伤模型.将C57BL/6小鼠随机分为空白组(0.9％NaCl)、模型组(小鼠肾损伤模型)和低、中、高剂量实验组组(0.53、1.05、2.10 g·kg-1·d-1 YSSX灌胃7 d).用蛋白质印迹法测定Keap1、Nrf2表达水平;用分光光度法测定超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)活性.结果 空白组、模型组和低、中、高剂量实验组的Keap1蛋白表达水平分别为0.26±0.02、0.64±0.03、0.59±0.01、0.45±0.05和0.34±0.02;Nrf2 蛋白表达水平分别为 0.69±0.06、0.35±0.01、0.36±0.01、0.48±0.02 和 0.56±0.01;CAT 活性分别为(572.49±912.92)、(334.60±4.92)、(402.76±9.80)、(475.35±5.21)和(493.00±12.03)U·mg-1;GSH 活性分别为(2.79±0.06)、(0.51±0.01)、(0.59±0.07)、(1.29±0.04)和(1.70±0.08)pmol·L-1;SOD 活性分别为(477.00±4.32)、(260.67±6.13)、(272.67±2.87)、(386.33±3.68)和(395.00±12.25)U·mL-1;MDA 活性分别为(3.89±0.02)、(7.32±0.03)、(6.94±0.14)、(4.60±0.01)和(4.34±0.02)nmol·mg·prot-1.模型组上述指标与空白组比较,在统计学上差异均有统计学意义(P＜0.01,P＜0.001);中、高剂量实验组上述指标与模型组比较,在统计学上差异均有统计学意义(P＜0.01,P＜0.001).结论 YSSX可以通过激活Keap1/Nrf2信号通路,调节机体氧化应激状态从而改善化疗导致的小鼠肾损伤.
Objective To study the effect and mechanism of action of Yi Sui Sheng Xue Fang(YSSX)in ameliorating chemotherapy-induced renal injury in mice through The Kelch-like ECH-associated protein 1(KEAP1)/Nuclear factor erythroid-derived 2-like 2(NRF2)signalling pathway.Methods A mouse kidney injury model was induced by intraperitoneal injection of carboplatin(40 mg·kg-1).C57BL/6 mice were randomly divided into blank group(0.9％NaCl),model group(kidney injury model)and experimental-L,experimental-M,experimental-H groups(0.53,1.05 and 2.10 g·kg-1·d-1 YSSX by gavage for 7 d).Keap1 and Nrf2 were determined by Western blot;superoxide dismutase(SOD)and malondialdehyde(MDA)activities were determined by spectrophotometry.Results The protein expression levels of Keap1 in blank group,model group and experimental-L,experimental-M,experimental-H groups were 0.26±0.02,0.64±0.03,0.59±0.01,0.45±0.05 and 0.34±0.02;the protein expression levels of Nrf2 were 0.69±0.06,0.35±0.01,0.36±0.01,0.48±0.02 and 0.56±0.01;the enzyme activities of catalase(CAT)were(572.49±912.92),(334.60±4.92),(402.76±9.80),(475.35±5.21)and(493.00±12.03)U·mg-1;glutathione(GSH)were(2.79±0.06),(0.51±0.01),(0.59±0.07),(1.29±0.04)and(1.70±0.08)μmol·L1;SOD were(477.00±4.32),(260.67±6.13),(272.67±2.87),(386.33±3.68)and(395.00±12.25)U·mL-1;MDA were(3.89±0.02),(7.32±0.03),(6.94±0.14),(4.60±0.01)and(4.34±0.02)nmol·mg prot-1.The differences of the above indexes in the model group compared with the blank group were statistically significant(P＜0.01,P＜0.001);the differences of the above indexes in experimental-M,experimental-H groups compared withe model group were statistically significant(P＜0.01,P＜0.001).Conclusion YSSX can activate Keap1/Nrf2 signaling pathway and regulate the oxidative stress state of the organism,thus improving the renal injury caused by chemotherapy in mice.
刘瑜;张志明;张利英;祁亚锋;李洋洋;张尚祖;徐倩;郝国雄;牛帆;刘永琦
甘肃中医药大学甘肃省高校重大疾病分子医学与中医药防治研究重点实验室,甘肃兰州 730000甘肃省中医院肿瘤科,甘肃兰州 730000甘肃中医药大学甘肃省高校重大疾病分子医学与中医药防治研究重点实验室,甘肃兰州 730000||甘肃省心血管病研究所,甘肃兰州 730000甘肃中医药大学附属医院急诊科,甘肃兰州 730000
中医学
益髓生血方;肾损伤;氧化应激;Kelch样环氧氯丙烷相关蛋白1;核因子E2相关因子2
Yi Sui Sheng Xue Fang;kidney injury;oxidative stress;Kelch-like ECH associated protein 1;nuclear factor erythroid2-related factor 2
《中国临床药理学杂志》 2024 (005)
703-707 / 5
高端人才承担省级科技计划基金资助项目("长江学者奖励计划")(22ZD1FA001);甘肃省中西医结合肿瘤临床医学研究中心开放基金资助项目(18JR2FA001-2,18JR2FA001-3);甘肃省科技重大专项基金资助项目(甘科技[2022]1号-25)
10.13699/j.cnki.1001-6821.2024.05.015
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