制大黄-川芎药对对CIN大鼠肾组织Nrf2/HO-1信号通路的影响  

Effects of Couplet Medicines of Prepared Radix et Rhizoma Rhei-Rhizoma Ligustici Chuanxiong on Nrf2/HO-1 Signaling Pathway in Renal Tissue of Contrast-induced Nephropathy Rats

作　　者：龚学忠[1] 邱安东 段怡汝 叶紫 郑君丽[1] 王骞[1] 王国华[3] 王跃荣[4] 

机构地区：[1]上海中医药大学附属市中医医院肾内科,上海200071 [2]同济大学生命科学与技术学院,上海200092 [3]上海中医药大学附属市中医医院实验中心,上海200071 [4]上海中医药大学附属市中医医院检验科,上海200071

出　　处：《上海中医药大学学报》2017年第6期58-61,共4页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81573936;81373614);上海市浦江人才计划项目(15PJD036);上海市卫计委转化医学重点项目(201540378);上海申康医院发展中心新兴前沿项目(SHDC12015126)

摘　　要：目的:在前期发现制大黄-川芎药对能抑制对比剂肾病(contrast-induced nephropathy,CIN)大鼠肾小管上皮细胞凋亡的基础上,进一步从核因子E2相关因子/血红素加氧酶-1(Nrf2/HO-1)通路探讨该药对的作用机制。方法:将32只雄性SD大鼠分为正常组(A组)、模型组(B组)、药对组(C组)、N-乙酰半胱氨酸(NAC)组(D组)。C组于造模前7 d每日灌胃制大黄-川芎水煎液,D组造模前3 d每日腹腔注射NAC(150μg/g)。B、C、D三组按照文献方法制备CIN模型。造模后24 h处死动物,并腹主动脉采取血测定血清肌酐(Scr)、尿素氮(BUN);代谢笼收集24 h尿液,并测定尿液中急性肾损伤(AKI)标志物N-乙酰-β-D氨基葡萄糖苷酶(NAG)、γ-谷氨酰转肽酶(U-γ-GT);分别提取肾组织中核蛋白和总蛋白,采用Western blotting方法检测肾组织中Nrf2和HO-1蛋白表达。结果:与A组比较,B组大鼠Scr、BUN、尿NAG、U-γ-GT均明显升高(P<0.01),肾组织中Nrf2、HO-1蛋白表达明显上调(P<0.01);与B组比较,C、D组Scr、BUN明显降低(P<0.05),尿NAG、U-γ-GT显著降低(P<0.01),Nrf2、HO-1蛋白表达显著降低(P<0.01)。结论:Nrf2/HO-1通路活化参与了CIN大鼠急性肾损伤过程,且制大黄-川芎药对可通过抑制该通路活化保护CIN大鼠肾功能。Objective： Based on the previous experiment results that couplet medicines of prepared Radix et Rhizoma Rhei- Rhizoma Ligustici Chuanxiong could inhibit the apoptesis of renal tubular epithelial cells in contrast-induced nephropathy （CIN）rats,to further explore the mechanism of this couplet medicines on nuclear factor erythroid 2-related factor 2 （Nrf2）/ heine oxygcuase- 1 （ HO- 1 ） pathway. Methods： Thirty-two male SD rats were divided into the normal group （ group A）, model group（ group B）, couplet medicines group （group C）and N-acetyl cysteine （NAC）group （group D）. From 7 days before modeling,the rats in the group C were daily treated with the decoction of this couplet medicines by intragastric administration. From 3 days before modeling, the rats in the group D were dally treated with NAC by intraperitoneal injection at dose of 150μg/g. According to the method in literatures,the CIN rat model was established in the groups B,C and D. 24 hours after modeling,the rats were sacrificed. The blood was collected from abdominal aorta and the serum levels of creafinine（Scr） and urea nitrogen（BUN）were detected. The urine was collected for 24 hours by metabolic cage, and the urinary levels of acute kidney injury （AKI） markers including N-acetyl-{3-D-glucosaminidase （NAG） and γ-glutamyl transpeptidase （U-γ-GT） were detected. The nuclear protein and total protein were extracted from renal tissue respectively, and the protein expressions of Nrt2 and HO-1 in the renal tissue were determined by Western blot. Results： Compared with the group A, the serum levels of Scr and BUN and urinary levels of NAG and U-γ-GT were all obviously increased in the group B （ P 〈 0. 01 ）, and the protein expressions of Nrt2 and HO-1 in the renal tissue were obviously up-regulated（ P 〈 0.01 ）. Compared with the group B, the serum levels of Scr and BUN were obviously decreased in the groups C and D（ P 〈 0.05 ）, and the urinary levels of NAG and U-γ-GT were significan

关 键 词：对比剂肾病 制大黄 川芎 对药 核因子E2相关因子 血红素加氧酶-1 

分 类 号：R285.5[医药卫生—中药学]