制大黄-川芎药对通过TLR4/Myd88/NF-κB信号对造影剂诱导大鼠肾小管上皮细胞凋亡及肾组织炎症因子IL-6、IL-1β的影响  

Effect of Zhidahuang-Chuanxiong Drug Pair on apoptosis of rat renal tubular epithelial cells induced by contrast agent via TLR4/Myd88/NF-κB

作　　者：郝健 许丽萍 吕铁钢[3] HAO Jian;XU Li-Ping;LüTie-Gang(The Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,Mongolia,China)

机构地区：[1]内蒙古医科大学附属医院肾内科,内蒙古呼和浩特010050 [2]内蒙古医科大学基础医学院药理学教研室 [3]内蒙古医科大学附属医院影像室

出　　处：《中国老年学杂志》2018年第23期5772-5775,共4页Chinese Journal of Gerontology

基　　金：国家自然科学基金(81460145)

摘　　要：目的探讨制大黄-川芎药对对造影剂肾病(CIN)大鼠肾小管上皮细胞凋亡的影响及潜在作用机制,并检测其对肾组织炎症因子白细胞介素(IL)-6、IL-1β分泌的影响。方法 24只SD大鼠随机分为正常组(Control组)、模型组(CIN组)和制大黄-川芎药对组(Drug pair组),造模后处死,测量各组血清肌酐(Scr)、尿素氮(BUN)及肾脏指数,原位末端标记(TUNEL)染色法测各组肾小管上皮细胞凋亡变化,Western印迹检测各组肾组织凋亡蛋白Bcl-2、Bax及Toll样受体(TLR4)/髓样分化因子(Myd88)/核转录因子(NF)-κB通路蛋白表达变化,酶联免疫吸附法(ELISA)检测各组肾组织中炎性细胞因子IL-6、IL-1β分泌。结果与Con-trol组相比,CIN组Scr、BUN含量和肾指数均显著上高,肾小管上皮细胞凋亡率显著增加,Bcl-2表达显著降低,Bax表达显著升高,TLR4/Myd88/NF-κB通路活性和炎性细胞因子IL-6、IL-1β分泌显著增加(均P<0. 05); Drug pair组较CIN组Scr、BUN含量和肾指数均明显回落,肾小管上皮细胞凋亡率显著降低,Bcl-2表达显著增加,Bax表达显著降低,TLR4/Myd88/NF-κB通路活性和炎性细胞因子IL-6、IL-1β分泌显著降低。结论制大黄-川芎药对可能通过TLR4/Myd88/NF-κB信号通路减少造影剂诱导的炎性细胞因子IL-6、IL-1β分泌,进而抑制了CIN大鼠肾小管上皮细胞凋亡,发挥保护作用。Objective To investigate the effects of Zhidahuang-Chuanxiong Drug Pair on apoptosis of renal tubular epithelial cellsinduced by contrast agent and its potential mechanism. Methods Twenty-four SD rats were randomly divided into control,model (CIN) andZhidahuang-Chuanxiong Drug Pair (drug pair) groups. All rats were killed after injection of contrast media for 24 h. The kidney injury wasassessed by the levels of serun creatinine (Scr),urea nitrogen (BUN),and kidney index. TUNEL staining was used to measure the apopto-sis of renal tubular epithelial cells,and the protein levels of Bcl-2,Bax and TLR4/Myd88/NF-κB pathway protein in renal tissue were detec-ted by Western blot. The levels of inflammatory cytokines IL-6 and IL-1β in renal tissue were detected by ELISA. Results Compared withthose of control group,the levels of Scr,BUN and renal index in CIN group were significantly higher,tubular epithelial cell apoptosis,pro-apoptotic protein Bax expression,TLR4/Myd88/NF-κB pathway protenin levels and the secretion of inflammatory cytokines IL-6 and IL-1βwere increased,while anti-apoptotic protein Bcl-2 was significantly decreased,and they were decreased in drug pair group,while the expres-sion of anti-apoptotic protein Bcl-2 was increased. Conclusions Zhidahuang-Chuanxiong Drug Pair could reduce the secretion of inflammato-ry cytokines IL-6,IL-1β and inhibit the apoptosis of renal tubular epithelial cells in SD rats induced by contrast agent through TLR4/Myd88/NF-κB signaling pathway,and then play an important role in protecting contrast induced nephropathy.

关 键 词：造影剂肾病 肾小管上皮细胞 制大黄-川芎药对 Toll样受体4/髓样分化因子88/核转录因子-κB 细胞凋亡 

分 类 号：R692[医药卫生—泌尿科学]