文献类型：期刊文献

中文题名：归芪白术方对顺铂所致小鼠肾脏损伤的减毒作用

英文题名：Attenuation effect of Guiqi Baizhu prescription on renal injury induced by cisplatin

作者：王磊[1,2];许小敏[1];张艳辉[1];刘永琦[1];张利英[1];张丽昕[1];张苡铭[1];何进鹏[3];危文俊[3]

第一作者：王磊

机构：[1]甘肃中医药大学,兰州730000;[2]重庆市云阳县中医院肿瘤科,重庆云阳404500;[3]中国科学院近代物理研究所,兰州730000

第一机构：甘肃中医药大学

年份：2018

卷号：43

期号：11

起止页码：917

中文期刊名：解放军医学杂志

外文期刊名：Medical Journal of Chinese People's Liberation Army

收录：CSTPCD;;Scopus;北大核心:【北大核心2017】；CSCD:【CSCD2017_2018】；

基金：甘肃中医药大学研究生创新基金(2017CX30).

语种：中文

中文关键词：归芪白术方;顺铂;肾脏损伤

外文关键词：Guiqi Baizhu prescription;cisplatin;renal injury

摘要：目的探讨益气补血、活血解毒经验药方归芪白术方对顺铂所致小鼠肾脏损伤的减毒作用。方法 50只雄性昆明小鼠随机分为空白组、模型组及归芪白术方低、中、高剂量组(n=10)。模型组及归芪白术方低、中、高剂量组每7d注射一次顺铂(剂量2.0mg/kg,每次0.2ml),共注射4次。归芪白术方低、中、高剂量组每日17:00用归芪白术方灌胃,每次0.4ml;空白组与模型组每日17:00采用等量生理盐水灌胃。每2d测量一次小鼠体重,每4d测量一次饮食情况,末次注射顺铂后48h采血检测各组小鼠血常规及肾脏功能,剥离各组小鼠肾脏组织,观察肾脏大体形态变化并计算肾脏指数,检测肾脏病理变化及肾脏组织中caspase 3、caspase 9的表达变化。结果空白组小鼠体重和饮食量维持在一个较高的平均水平;模型组小鼠体重呈周期性地降低和恢复,饮食量则明显降低;给药(归芪白术方)后,小鼠体重和饮食的降低得到一定缓解。肾脏大体观可见空白组小鼠肾脏颜色深而富有血液;模型组小鼠肾脏颜色明显变浅,体积变小,肾脏指数明显降低;给药(归芪白术方)后,肾脏体积有所增加,颜色较模型组加深,肾脏指数升高,其中,中、高剂量组改善较明显,与模型组比较差异有统计学意义(P<0.05)。与空白组比较,模型组小鼠白细胞计数(WBC)、血小板计数(PLT)明显降低,尿素氮(BUN)、血肌酐(Scr)水平及caspase3、caspase9表达量明显升高,差异均有统计学意义(P<0.05);与模型组比较,归芪白术方低、中、高剂量组小鼠WBC、PLT明显升高,BUN、Scr水平降低,caspase 3、caspase 9表达量明显下调,以中、高剂量最为明显,差异有统计学意义(P<0.05),低剂量组Scr水平与模型组比较差异无统计学意义。病理形态学观察显示,空白组小鼠肾脏组织结构正常,无明显变性、坏死及炎性浸润,可见到清晰的肾小管结构;模型组小鼠肾小管结构浊肿,近曲小管上皮细胞有较多的气球样变,部分萎缩或消失;给药(归芪白术方)后,各组小鼠肾脏病理损伤减轻,肾小管浊肿程度得到缓解,气球样变和萎缩的肾小管上皮细胞较模型组明显减少。结论归芪白术方对顺铂所致肾脏损伤具有减毒作用,其机制可能是通过益气补血、活血解毒等作用来改善血液活力、减少肾脏组织细胞的凋亡,从而减轻顺铂对肾脏组织的损伤。
Objective To explore the attenuation effect of Guiqi Baizhu prescripion on kidney injury induced by cisplatin in mice. Methods Fifty male Kunming mice were randomly divided into 5 groups(10 each): blank group, model group, and low, medium, and high dose of Guiqi Baizhu prescripion group. Mice in the 4 latter groups were intraperitoneally injected with cisplatin(2.0mg/kg, 0.2ml) once every 7d for 4 times. Mice in the 3 latter groups were gavaged with Guiqi Baizhu prescripion(0.4ml) at 17:00 every day, and in blank group and model group were gavaged with equivalent normal saline at 17:00 every day. The weight of mice was detected every 2 days, and the appetite was detected every 4 days. Blood routine and renal function tests were performed 48 hours after the last cisplatin injection, and the kidney tissues of all the mice were stripped, the general morphological changes of kidney were observed, the kidney index was calculated, and the renal pathological changes and the expression of cysteinyl aspartate specific proteinase 3(caspase 3) and cysteinyl aspartate specific proteinase 9(caspase 9) in kidney tissue were also detected. Results The body weight and appetite of control group were maintained in a higher average level, while the body weight of model group showed cyclical decrease and recovery, and the appetite presented significant reduction. After administration of Guiqi Baizhu prescription, the reduction of body weight and appetite got some mitigation. As to the general morphology of the kidney, those in blank group were with deep color and rich blood, and in model group with apparently lighter colour, smaller volume, and significantly decreased kidney index. After administration of Guiqi Baizhu prescription, the kidney volume increased, color deepened, and kidney index increased compared with that in model group, and these changes were more obvious in medium and high dose group with significant difference compared to that in model group(P<0.05). As to the biochemical function, the white blood cell count(WBC) and platelet count(PLT) decreased significantly, while the contents of urea nitrogen(BUN) and serum creatinine(Scr) and the expressions of caspase 3 and caspase 9 increased significantly in model group than in blank group with statistically significant difference(P<0.05). Compared with that of model group, the WBC and PLT counts increased significantly, and the contents of BUN and Scr, and the expressions of caspase 3 and caspase 9 decreased significantly in the 3 groups of Guiqi Baizhu prescription administration with statistically significant difference(P<0.05). As to the pathological aspects, the organizational structure of kidney tissue in blank group was normal, with no obvious degeneration, necrosis and inflammatory infiltration, and with clear renal tubular structure;while the kidney tissue of model group appeared abnormal structure, renal tubules turbid swelling, proximal convoluted tubule epithelial cells with ballooning, atrophy and disappearance;administration of Guiqi Baizhu prescription reduced the renal pathological damage and renal tubular turbid swelling, and ballooning degenerated and the atrophy of renal tubular epithelial cells was significantly reduced. Conclusion Guiqi Baizhu prescription may provide with attenuated effect to renal injury induced by cisplatin with a possible mechanism of improving blood vitality and reducing apoptosis of renal cells by supplementing Qi and enriching blood, so as to reduce the damage effect of cisplatin on kidney tissue.