白豆蔻对大鼠阿霉素肾病的作用机制及与STAT1-P53-P21信号通路表达的关系  

Amomum kravanh alleviates doxorubicin nephropathy in rats by regulating STAT1-P53-P21 signaling pathway

作　　者：王勤超[1] 苏伟[1] 马世兴[1] 仇琳[1] WANG Qinchao;SU Wei;MA Shixing;QIU Lin(Baoji Central Hospital,Baoji 721008,Shanxi,China)

机构地区：[1]宝鸡市中心医院,陕西宝鸡721008

出　　处：《西部医学》2020年第10期1432-1437,共6页Medical Journal of West China

基　　金：陕西省社会发展科技攻关项目(2016SF-187)。

摘　　要：目的研究白豆蔻对大鼠阿霉素肾病的作用机制及与STAT1-p53-p21信号通路表达的关系。方法选择雄性SD大鼠120只,随机分为正常对照组、模型对照组、白豆蔻低剂量组、白豆蔻中剂量组、白豆蔻高剂量组、贝那普利组。采用1次性尾静脉注射10 mg/kg阿霉素构建阿霉素肾病模型,在造模后第4 d开始给药,白豆蔻低、中、高剂量组大鼠分别每天灌胃1.5、3.0、4.5 g/kg白豆蔻,贝那普利组大鼠每天灌胃10 mg/kg贝那普利,模型对照组和正常对照组大鼠灌胃等量生理盐水,每日一次,持续4周。通过尿液分析仪检测尿液尿蛋白(PRO)、尿隐血(BLO)和胆红素(BIL)含量,通过全自动生化分析仪检测大鼠血清总胆固醇(TC)、甘油三酯(TG)、总蛋白(TP)、白蛋白(ALB)、尿素氮(BUN)、肌酐(Scr)水平,通过HE染色观察肾组织损伤,通过流式检测肾细胞凋亡情况,通过Western blot检测caspase-3、Bax、Bcl-2、STAT1、p53和p21的表达,通过试剂盒检测SOD和MDA的含量,通过ELISA检测血清中炎症因子IL-1β、IL-6和TNF-α的水平。结果给药各组大鼠与模型对照组相比,尿液中PRO、BLO和BIL含量及血液中TC、TG、BUN和Scr含量均有不同程度的降低,血液中TP和ALB含量均有不同程度的升高,肾小球病症均有不同程度减轻,肾细胞凋亡率、caspase-3和Bax蛋白表达量均有不同程度的降低,Bcl-2蛋白表达量均有不同程度的升高,MDA含和IL-1β、IL-6和TNF-α含量均有不同程度的降低,SOD活性均有不同程度的升高,STAT1、P53和P21蛋白表达量均有不同程度的降低,且白豆蔻中剂量组的作用最显著。结论白豆蔻可通过调控STAT1-P53-P21信号通路减轻大鼠阿霉素肾病。Objective To study the mechanism of Amomum kravanh on doxorubicin-induced nephropathy in rats and its relationship with the expression of STAT1-p53-p21 signaling pathway.Methods A total of 120 male SD rats were randomly divided into normal control group,model control group,Amomum kravanh low dose group,Amomum kravanh medium dose group,Amomum kravanh high dose group and benazepril group.A doxorubicin nephropathy model was constructed by a single tail vein injection of 10 mg/kg doxorubicin.The drug was administered on the fourth day after modeling,and the rats in the low,medium and high doses of Amomum kravanh were intragastrically administered with 1.5,3.0,4.5 g/kg white soybean.Rats in the benazepril group were intragastrically administered with 10 mg/kg benazepril daily.The rats in the model control group and the normal control group were given the same amount of normal saline once a day for four weeks.The amount of PRO,BLO,BIL in the urine is detected by a urine analyzer.The levels of TC,TG,TP,ALB,BUN,and Scr in the serum of rats were detected by an automatic biochemical analyzer.Renal tissue damage was observed by HE staining.Renal cell apoptosis is detected by flowmetry.The expression of caspase-3,Bax,Bcl-2,STAT1,p53 and p21 was detected by Western blot.The content of SOD and MDA is detected by a kit,Serum levels of inflammatory factors IL-1β,IL-6 and TNF-αwere measured by ELISA.Results Rats in each group fed the drug compared with the model control group.The contents of PRO,BLO and BIL in urine and the contents of TC,TG,BUN and Scr in blood were all reduced to varying degrees.The levels of TP and ALB in the blood increased to varying degrees.Glomerular disorders are all reduced to varying degrees.Renal cell apoptosis rate,caspase-3 and Bax protein expression levels were all reduced to varying degrees.The expression level of Bcl-2 protein increased to varying degrees.MDA content and IL-1,IL-6 and TNF-αlevels were reduced to varying degrees.SOD activity has increased to varying degrees.The expression levels

关 键 词：白豆蔻 阿霉素肾病 STAT1 P53 P21 

分 类 号：R692[医药卫生—泌尿科学]