益母草碱调控水通道蛋白减轻急性肾损伤  

Leonurine Ameliorates Acute Kidney Injury via Regulating Aquaporins

作　　者：黄丽华 程冉[1,2] 徐鹏 王晓婉 郭珊[1,2] 吴爱君 黎创 毛炜 田瑞敏[1,2,3,4] HUANG Li-hua;CHENG Ran;XU Peng;WANG Xiao-wan;GUO Shan;WU Ai-jun;LI Chuang;MAO Wei;TIAN Rui-min(State Key Laboratory of Dampness Syndrome of Chinese Medicine,The Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou,510120;The Second Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou,510405;Department of Nephrology,Guangdong Provincial Hospital of Chinese Medicine,Guangzhou,510120;Faculty of Chinese Medicine,Macao University of Science and Technology,Macao,999078,China)

机构地区：[1]省部共建中医湿证国家重点实验室,广州中医药大学第二附属医院,广州510120 [2]广州中医药大学第二临床医学院,广州510405 [3]广东省中医院肾内科,广州510120 [4]澳门科技大学中医药学院,中国澳门999078

出　　处：《中国中西医结合杂志》2025年第1期77-82,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.82004157);广东省中医药局科研项目(No.20225002);广东省中医院朝阳人才科研专项(No.ZY2022KY13);省部共建中医湿证国家重点实验室专项(No.SZ2021ZZ10)。

摘　　要：目的从水通道蛋白(AQP)角度探讨活血利水中药益母草活性成分益母草碱对急性肾损伤(AKI)的作用及机制。方法将40只C57BL/6小鼠随机分为正常组、模型组及益母草碱低、中、高剂量组,每组8只。除正常组外,各组小鼠通过腹腔注射顺铂构建AKI模型;药物组预给药3天,低、中、高剂量组分别每日晨予以20、40、80 mg/kg益母草碱灌胃,连续7天;空白组与模型组予以等体积的纯水灌胃。造模72 h后取材,检测小鼠血肌酐与尿素氮水平,以筛选最佳剂量;HE染色观察肾脏病理变化;免疫组化检测肾组织中AQP各亚型(AQP1~4)的位置及相对表达;Western Blot法检测肾组织中AQP1~4蛋白表达水平。结果与正常组比较,模型组小鼠的肌酐和尿素氮水平升高(P<0.05)。肾脏病理染色显示,模型组的肾小管发生局灶性病变,部分小管细胞腔面刷状缘脱落,细胞扁平,而益母草碱治疗组较模型组病变明显减少。与正常组比较,模型组小鼠AQP1、AQP2、AQP4蛋白表达均降低(P<0.01,P<0.05)。与模型组比较,益母草碱高剂量组肌酐、尿素氮水平降低,AQP1、AQP3蛋白表达均升高(P<0.01,P<0.05)。结论益母草碱可以降低AKI小鼠的肌酐和尿素氮水平,减轻肾脏病理损伤,其机制可能与调控AQP密切相关。Objective To investigate the effects and mechanisms of leonurine,an active component of Chinese motherwort(Leonurus japonicus Houtt.)which capable of activating blood circulation and eliminating water-dampness,on acute kidney injury(AKI)from the perspective of aquaporins(AQP).Methods Forty C57BL/6 mice were randomly divided into control group,AKI model group,and leonurine treatment groups(low-dose,medium-dose and high-dose),with 8 mice in each group.Except for the control group,mice in each group were intraperitoneally injected with cisplatin to construct the AKI model.The intervention groups were pre-administered with leonurine for 3 days before modeling,and lasted for 7 consecutive days,with the dosages of 20,40,80 mg/kg,respectively.Control group and model group were gavaged with the equal volume of purified water.After 72 hours of modeling,the serum creatinine and urea nitrogen levels of all mice were examined to determine the optimal dose of leonurine.HE staining was performed to observe the pathological changes of kidneys.Immunohistochemistry and Western Blot were performed to detect the location and relative expression of the AQPs(AQP1-4)among different groups.Results Compared with the control group,the creatinine and urea nitrogen levels in model group were significantly increased(P<0.05).Renal pathological staining showed that,compared with the control group,the renal tubules in the model group had focal lesions,with some of the luminal surfaces of tubular cells with brush border detachment and cell flattening,whereas the lesions in the leonurine-treated group were significantly reduced.Compared with the control group,the protein expressions of AQP1,AQP2 and AQP4 in mice of the model group were significantly reduced(P<0.01,P<0.05).Compared with the model group,the creatinine and urea nitrogen levels reduced,and the protein expressions of AQP1 and AQP3 were elevated in the high-dose leonurine treatment group(P<0.01,P<0.05).Conclusion Leonurine can reduce creatinine and urea nitrogen levels and alleviate r

关 键 词：急性肾损伤 活血利水 益母草 益母草碱 水通道蛋白 中药 

分 类 号：R285.5[医药卫生—中药学]