加味四君子汤对阿霉素肾病大鼠胫骨细胞核因子-κB信号通路的影响  

The effects of the Sijunzi decoction on NF-κB signal pathway in tibial cells of rats with adriamycin-induced nephropathy

作　　者：陈敏[1] 赖晶晶 陈虹[1] 陈小英[1] 郑京[1] CHEN Min

机构地区：[1]福建中医药大学附属人民医院,福建福州350004 [2]福建中医药大学,福建福州350122

出　　处：《中医临床研究》2021年第31期26-29,共4页Clinical Journal Of Chinese Medicine

基　　金：福建省中医药科技项目(2017FJZYJC203);福建省医学创新课题(2017-CX-41)。

摘　　要：目的:探讨加味四君子汤对泼尼松干预的阿霉素肾病大鼠胫骨细胞中核因子(Nuclear Factor,NF)-κB通路的影响。方法:通过尾静脉注射盐酸阿霉素造模,将40只阿霉素肾病大鼠模型按照分层随机法分为5组:正常组(N组)、模型组(M组,予阿霉素溶液注射尾静脉)、激素组(A组,予泼尼松)、中药组(B组,予中药)、中药加激素组(C组,予中药加泼尼松),连续灌胃14d。尿液标本在注射阿霉素造模后的第7、14天后采集。光镜下观察胫骨组织学形态。采用实时荧光定量聚合酶链式反应(Polymerase Chain Reaction,PCR)、蛋白质印迹(Western Blotting)法检测核因子-κB受体活化因子配体(Receptor Activator of NF-κB Ligand,RANKL),核因子-κB受体活化因子(Receptor Activator of NF-κB,RANK)和p38丝裂原活化蛋白激酶(p38 Mitogenactivated Protein Kinase,p38 MAPK)的mRNA和蛋白在胫骨细胞中的表达情况。用凝胶电泳迁移分析法(Electrophoreticmobility Shift Assays,EMSA)检测NF-κB浓度。结果:与N组相比,M组第7、14天尿蛋白升高;各治疗组与M组相比尿蛋白均下降(P<0.01)。光镜下A组骨小梁排列相对紊乱,B、C组骨组织形态得到改善。与N组相比,M组RANKL、RANK、p38 MAPK的mRNA及蛋白水平均升高,NF-κB表达增多。与M组相比,A组均升高,B、C组均降低;与A组相比,B、C两组均降低(P<0.01)。结论:加味四君子汤在减轻尿蛋白的同时,可以通过抑制骨组织RANK-RANKL-p38 MAPK-NF-κB通路抑制破骨细胞分化。Objective:To investigate the effects of the Sijunzi decoction(四君子汤)plus prednisone on NF-κB pathway in tibial cells of rats with adriamycin-induced nephropathy.Methods:The rat models were established by injecting doxorubicin hydrochloride into the tail vein,and 40 adriamycin nephrotic rat models were divided into 5 groups according to the stratified random method,namely the normal group(the group N),the model group(the group M,took doxorubicin solution injection into the tail vein),the hormone group(the group A,took prednisone),the traditional Chinese medicine group(the group B,received Chinese materia medica),and the Chinese materia medica plus hormone group(group C,took Chinese materia medica plus prednisone).Gavage lasted for 14 consecutive days.Urine samples were collected 7 and 14 days after injectioning doxorubicin hydrochloride.The histological morphology of tibia was observed under a light microscope.Real-time fluorescent quantitative PCR and Western blotting were used to detect the expression of mRNA and protein of RANKL,RANK,and p38 MAPK in tibial cells.The concentration of NF-κB was detected by EMSA.Results:Compared with the group N,the urine protein in group M was increased on the 7th and 14th day,and the urine protein in all treatment groups was more decreased compared with group M(P<0.01).Under the light microscope,the arrangement of bone trabeculae was relatively disordered in the group A,and the bone morphology was ameliorated in group B and group C.Compared with group N,the mRNA and protein levels of RANKL,RANK and p38 MAPK in the group M were rised,and the expression of NF-κB was increased.Compared with the group M,the related indicators were increased in the group A,and were decreased in the group B and group C.Compared with the group A,the related indicators were decreased in group B and the group C(P<0.01).Conclusion:In addition to reducing urinary protein,the Sijunzi decoction can inhibit osteoclast differentiation by inhibiting RANK-RANKL-p38 MAPK-NF-κB pathway in bone tissue.

关 键 词：核因子ΚB受体活化因子配体 核因子ΚB受体活化因子 p38丝裂原活化蛋白激酶 核因子-κB 加味四君子汤 

分 类 号：R284.5[医药卫生—中药学]