毛蕊异黄酮在顺铂诱导的小鼠急性肾损伤中抗氧化机制的研究  

Antioxidant effect of calycosin on cisplatin-induced acute kidney injury in mice

作　　者：廖奕娇 刘佳惠 刘新辉 杨曙东[1] LIAO Yijiao;LIU Jiahui;LIU Xinhui;YANG Shudong(Shenzhen Traditional Chinese Medicine Hospital,Shenzhen 518033,China)

机构地区：[1]深圳市中医院,广东深圳518033

出　　处：《中国病理生理杂志》2025年第4期750-756,共7页Chinese Journal of Pathophysiology

基　　金：深圳市科创委(No.JCYJ20240813152342056,No.JCYJ20220531092214032);深圳市‘医疗三名工程’资助项目(No.SZZYSM202311004)。

摘　　要：目的:观察毛蕊异黄酮(calycosin,CA)对急性肾损伤(acute kidney injury,AKI)小鼠肾脏结构的影响及相关的抗氧化作用机制。方法:将30只雄性C57BL/6J小鼠分为对照组、模型组与治疗组,其中CA治疗组分为低、中、高剂量CA组,分别给予5 mg/kg、10 mg/kg、20 mg/kg的CA溶液提前每天连续灌胃给药6 d,随后模型组和治疗组予腹腔注射20 mg/kg顺铂(cisplatin,CDDP)诱导AKI小鼠模型,造模72 h后留取小鼠标本。测量各组小鼠体重和双侧肾脏平均质量;检测血清肌酐(serum creatinine,SCr)和血尿素氮(blood urea nitrogen,BUN);采用过碘酸希夫(periodic acid-Schiff,PAS)染色法观察小鼠的肾脏病理改变;通过Western blot法、免疫组化染色法检测各组小鼠肾脏的超氧化物歧化酶1(superoxide dismutase 1,SOD1)、SOD2、谷胱甘肽过氧化酶1(glutathione peroxidase 1,GPX1)和过氧化氢酶(catalase)的蛋白表达。结果:与对照组比较,模型组小鼠体质量显著下降,双侧肾脏平均质量则显著增加,SCr和BUN均显著升高(P<0.01);PAS显示肾小球和肾小管结构损伤明显,肾小管管型广泛出现;Western blot法检测出SOD1、SOD2、GPX1和catalase蛋白表达水平降低(P<0.05),与免疫组化染色结果显示一致。与模型组比较,低剂量CA组和中剂量CA组小鼠体重显著增加,CA治疗组双侧肾脏平均质量均显著下降(P<0.05);SCr和BUN均显著降低(P<0.01);PAS提示CA治疗后肾小球和肾小管结构明显恢复;中剂量CA组和高剂量CA组肾组织中SOD1、GPX1表达升高(P<0.05),中剂量CA组的SOD2和catalase蛋白表达水平显著升高(P<0.05)。结论:CA可以减轻CDDP诱导的AKI小鼠肾脏损伤,其作用机制与增加抗氧化酶SOD1、SOD2、GPX1和catalase的表达相关。AIM:To investigate the protective mechanism of calycosin(CA)on renal structure and antioxidant capacity in acute kidney injury(AKI)mice.METHODS:Thirty male C57BL/6J mice were allocated into control group,model group,and treatment group.The treatment group was further subdivided into low-dose CA,middle-dose CA,and high-dose CA groups,receiving 5 mg/kg,10 mg/kg,and 20 mg/kg CA solution by gavage for 6 days.After the pre-treatment phase,both the model and treatment groups were administered an intraperitoneal injection of 20 mg/kg of cisplatin(CDDP)to induce AKI modeling.Specimens from the mice were collected 72 hours post-modeling for further analysis.The body weight and the mean mass of both kidneys were assessed.Serum creatinine(SCr)and blood urea nitrogen(BUN)levels were assessed to evaluate kidney function.Kidney pathology was assessed with periodic acid-Schiff(PAS)staining,while protein levels of superoxide dismutase 1(SOD1),SOD2,glutathione peroxidase 1(GPX1),and catalase were evaluated using Western blot and immunohistochemistry assay.RESULTS:Compared with the control group,the model group exhibited a substantial reduction in body mass,a significant increase in the mean mass of bilateral kidneys,and elevated levels of SCr and BUN,indicating impaired renal function(P<0.01).PAS staining revealed pronounced structural damage to the glomeruli and renal tubules,with widespread appearance of tubular casts in model group.The results of Western blot and immunohistochemical staining demonstrated significantly reduced expression of antioxidant enzymes SOD1,SOD2,GPX1,and catalase(P<0.05).The body weight of mice in the low-dose and middle-dose CA groups exhibited a significant increase than those in the model group,and the kidney weights of mice in Low-dose,middle-dose,and high-dose CA groups were significantly lower than those of mice in the model group(P<0.05).Additionally,SCr and BUN levels were significantly reduced(P<0.01).PAS staining indicated obvious recovery of glomeruli and renal tubules after CA treatment.SOD1

关 键 词：毛蕊异黄酮 急性肾损伤 抗氧化 顺铂 

分 类 号：R692[医药卫生—泌尿科学] R285[医药卫生—外科学] R363.2[医药卫生—临床医学]