Page 62 - 《中国药房》2022年15期

金匮肾气丸对肾纤维化模型大鼠的干预作用及机制 Δ

张明昊 ，俎兆轩，张 童，郭 申，杜婧雯，赵 绅（河南中医药大学医学院，郑州 450046）
＊

中图分类号 R965 文献标志码 A 文章编号 1001-0408（2022）15-1848-07
DOI 10.6039/j.issn.1001-0408.2022.15.11

摘 要 目的 基于转化生长因子β 1/Smads（TGF-β 1/Smads）和TGF-β 1/细胞外信号调节激酶（TGF-β 1/ERK）信号通路探讨金匮肾气
丸对肾纤维化模型大鼠的干预作用及机制。方法 将雄性SD大鼠灌胃腺嘌呤混悬液（250 mg/kg）以复制肾纤维化模型，造模成功
后，按体质量随机分为模型组、秋水仙碱片组（阳性对照，0.45 mg/kg）和金匮肾气丸低、中、高剂量组（0.5、1、2 g/kg），每组10只；另
取10只健康大鼠作为正常组。各药物组大鼠灌胃相应药液，正常组和模型组大鼠均灌胃羧甲基纤维素钠溶液，每天1次，连续30
d。末次给药后，检测大鼠血清中肌酐（Cr）、尿素氮（BUN）水平以及肾脏质量和体质量，并计算BUN/Cr比值及肾脏系数；观察大
鼠肾脏组织的病理形态；检测大鼠肾脏组织中TGF-β 1、Smad2、Smad3、ERK1、ERK2蛋白和mRNA的表达水平。结果 与正常组比
较，模型组大鼠血清中Cr、BUN水平和肾脏系数均显著升高（P＜0.05），BUN/Cr比值显著降低（P＜0.05）；肾脏体积明显增大，表面
颗粒化严重，可见系膜增生，肾小管扩张或萎缩，并伴有大面积胶原蛋白沉积等；肾脏组织中TGF-β 1、Smad2、Smad3、ERK1、ERK2
蛋白和mRNA的表达水平均显著升高（P＜0.05）。与模型组比较，金匮肾气丸各剂量组大鼠上述指标水平均显著逆转（P＜0.05）；
肾小管扩张或萎缩减轻，胶原蛋白沉积不同程度地减少。结论 金匮肾气丸可改善肾纤维化模型大鼠的肾脏功能，其作用机制可
能与抑制TGF-β1/Smads和TGF-β1/ERK这2条信号通路有关。
关键词 金匮肾气丸；肾纤维化；TGF-β1/Smads信号通路；TGF-β1/ERK信号通路；机制

Intervention effects of Jinkui shenqi pills on renal fibrosis model rats and its mechanism
ZHANG Minghao，ZU Zhaoxuan，ZHANG Tong，GUO Shen，DU Jingwen，ZHAO Shen（School of Medicine，
Henan University of Chinese Medicine，Zhengzhou 450046，China）

ABSTRACT OBJECTIVE To investigate the intervention effect of Jinkui shenqi pills on renal fibrosis（RF）model rats and its
mechanism based on transforming growth factor β 1/Smads（TGF-β 1/Smads）and TGF-β 1/extracellular signal regulated kinase（ERK）
signaling pathway. METHODS Male SD rats were given adenine suspension（250 mg/kg）to induce RF model. After modeling，
they were randomly divided into model group，Colchicine tablet group （positive control，0.45 mg/kg） and Jinkui shenqi pills
low-dose，medium-dose and high-dose groups（0.5，1，2 g/kg），with 10 rats in each group. Other 10 healthy rats were selected as
normal group. The rats in administration groups were given the corresponding drugs intragastrically；normal group and model group
were given 0.1％ sodium carboxymethyl cellulose solution，once a day，for consecutive 30 d. After last medication，the serum
levels of creatinine（Cr）and blood urea nitrogen（BUN），renal weight and body weight were detected. The ratio of BUN/Cr and
renal coefficient were calculated. The pathological morphology of renal tissue in rats were observed. The protein and mRNA
expressions of TGF-β 1，Smad2，Smad3，ERK1 and ERK2 were detected. RESULTS Compared with normal group，serum levels
of Cr and BUN and renal coefficient were all increased significantly in model group（P＜0.05），while the ratio of BUN/Cr was
decreased significantly（P＜0.05）. The volume of the kidney was significantly increased，and the surface was seriously granulated.
Mesangial hyperplasia，dilation or atrophy of renal tubules，accompanied by large-area collagen deposition，could be found. Protein
and mRNA expressions of TGF-β 1，Smad2，Smad3，ERK1 and ERK2 were increased significantly in renal tissue （P＜0.05）.
Compared with model group，above indexes of Jinkui shenqi pills groups were all reversed significantly（P＜0.05）；dilation or
atrophy of renal tubules was relieved，and collagen deposition was reduced to different extents. CONCLUSIONS Jinkui shenqi
pills can improve renal function of RF model rats，the mechanism of which may be associated with inhibiting TGF-β 1/Smads and
TGF-β1/ERK signaling pathway.
KEYWORDS Jinkui shenqi pills；renal fibrosis；TGF-β1/Smads signaling pathway；TGF-β1/ERK signaling pathway；mechanism

肾纤维化（renal fibrosis，RF）是原发或继发慢性肾 润，肾小管上皮细胞也会凋亡，而来源于肾小管上皮细
脏病（chronic kidney disease，CKD）发展至终末期肾衰竭 胞-间充质转化（epithelial-mesenchymal transdifferentia-
的共同病理途径，以肾小管萎缩、肾小球硬化为主要特 tion，EMT）的肌成纤维细胞将会聚集并使细胞外基质
征 [1－2] 。当肾脏组织受损后，肾间质会出现炎症细胞浸 （extracellular matrix，ECM）的生成与降解失衡，从而导致
ECM过度沉积，进而引发RF [3－4] 。西医治疗RF主要为对
Δ 基金项目 河南省重点研发与推广专项（No.212102311132）
＊第一作者 高级实验师，硕士。研究方向：基础药理学。E-mail： 症治疗，即控制血压、血糖、血脂水平及抑制肾素-血管
[5]
zhangminghao@hactcm.edu.cn 紧张素系统，以达到控制原发病和防治并发症的目的 ，

·1848 · China Pharmacy 2022 Vol. 33 No. 15 中国药房 2022年第33卷第15期