黄芪山甲方抗肾间质纤维化的多靶点抑制作用  

Multi-target inhibition of Huangqishanjia (HQSJ) on renal interstitial fibrosis(RIF)

作　　者：蔡宏瑜[1] 杨光辉[1] 万强[1] 张娟[1] 傅志慧[1] 高艳霞[1] 

机构地区：[1]山西省中医院肾病科,山西太原030012

出　　处：《中国医药科学》2014年第20期7-12,26,共7页China Medicine And Pharmacy

基　　金：山西省基础研究项目(2011011039-2)

摘　　要：目的：动态观察黄芪山甲方（HQSJ）对大鼠肾间质纤维化（RIF）多靶点的治疗作用，探讨HQSJ方在不同阶段的可能作用机制。方法实验采用UUO大鼠模型，将雄性SD大鼠54只随机分成3组：假手术组（Sham）、模型组（UUO）、治疗组（HQSJ）。术后14、28、56d分别处死6只大鼠，观察肾功能变化；对肾小管基底膜（TBM）、肾小管萎缩、炎细胞浸润及间质纤维化情况进行半定量评分；采用免疫组织化学法及RT-PCR法检测肾组织TGF-β1、FN蛋白及mRNA的表达。结果（1）肾功能方面：与Sham组比较，UUO及HQSJ组大鼠BUN、SCr值在14～28d进行性升高，在28～56d相对稳定。HQSJ组大鼠BUN、SCr值在同一时相均较UUO组低（P＜0.05）。（2）病理改变方面：与Sham组比较，UUO及HQSJ组大鼠炎细胞浸润与肾间质慢性病变程度均有增高趋势，同一时相比较差异均有统计学意义（P＜0.05）。UUO与HQSJ组比较，炎细胞浸润程度在14、28d有统计学意义（P＜0.05），56d无统计学意义（P＞0.05）；肾间质慢性病变程度14、28、56d均有统计学意义（P＜0.05）。（3）TGF-β1、FN表达：与Sham组比较，UUO及HQSJ组TGF-β1、FN表达均增高，在同一时相比较均有统计学意义（P＜0.05）；与UUO组比较，HQSJ组TGF-β1、FN在14、28、56d的表达均不同程度下降（P＜0.05）；同一时相下降幅度比较：免疫组化示TGF-β1、FN蛋白阳性率分别下降64％、47％、7％及82％、72％、70％；RT-PCR法检测TGF-β1、FN的mRNA分别下降72％、57％、27％及83％、72％、68％。结论 HQSJ方抗肾间质纤维化的多靶点作用，可能与减少炎性细胞、抑制TGF-β1分泌，减轻肾脏固有细胞的活化及转分化，从而减少细胞外基质的沉积有关。其作用从病变早期开始，在14～28d主要是减少炎性细胞浸润和降低TGF-β1表达，对FN的抑制作用贯穿始终。Objective To observe the multi-target therapeutic effect of HQSJ for RIF of mice and discuss possible action mechanism of HQSJ in different stages. Methods UUO mice mode was adopted and 54 male SD mice were randomly divided into 3 groups as fake operation group （Sham）, model group （UUO） and treatment group （HQSJ）. 6 mice were killed separately on 14d, 28d and 56d after operation and their kidney function changes were observed;TBM, renal tubular atrophy, inflammatory cell infiltration and RIF were given semi-quantitative scores;TGF-β1, FN protein and mRNA expressions of renal tissues were detected by immunohistochemical method and RT-PCR method. Results （1） On kidney function, compared with Sham group, BUN and SCr values of UUO and HQSJ group were developed during 14-28d and stayed relatively steady during 28-56d. BUN and SCr values of HQSJ group were both lower than UUO group in the same time phase （P ＆lt; 0.05）. （2） On pathological chages, compared with Sham group, inflammatory cell infiltration and renal interstitial chronic lesion degrees of mice of UUO and HQSJ group both had a increasing trend in the same time phase （P＆lt;0.05）. There were significant differences between inflammatory cell infiltration of UUO group and HQSJ group on 14 and 28d （P ＆lt; 0.05） but no significant difference on 56d （P ＆gt; 0.05）; there were significant differences on renal interstitial chronic lesion degrees on 14, 28 and 56d （P＆lt;0.05）. （3） On TGF-β1, FN expressions：compared with Sham group, TGF-β1 and FN expressions of UUO and HQSJ group both rose in the same time phase （P＆lt;0.05）; compared with UUO group, TGF-β1 and FN expressions on 14, 28 and 56d of HQSJ group all declined to different extents （P＆lt;0.05）;decline degree of the same time phase comparison;immunohistochemical method showed that positive rates of TGF-β1 and FN protein declined separately by 64%, 47%, 7% and 82%, 72%, 70%; RT-PCR method showed that mRNA of TGF-β1 and FN declined separately

关 键 词：黄芪山甲方 肾间质纤维化 TGF-Β1 FN 

分 类 号：R277.5[医药卫生—中医学]