青蒿琥酯对糖尿病肾病大鼠肾组织Toll样受体4及白细胞介素-8表达的影响  

Effect of artesunate on expressions of Toll-like receptor 4 and interleukin-8 in renal tissues of diabetic nephropathy rats

作　　者：聂寒 苏珂[1] 龙艳[1] 蒋姗姗[1] 孙清[1] 

机构地区：[1]桂林医学院附属医院内分泌科,541001

出　　处：《天津医药》2015年第4期356-360,共5页Tianjin Medical Journal

基　　金：广西医疗卫生适宜技术研究与开发项目(S201316-07);广西自然科学基金项目(2012GXNSFAA053085)

摘　　要：目的观察青蒿琥酯对糖尿病肾病(DN)大鼠模型肾组织Toll样受体(TLR)4、白细胞介素(IL)-8表达的影响。方法健康雄性SD大鼠(体质量>200 g)采用高糖高脂联合腹腔注射30 mg/kg链脲佐菌素(STZ)法建立糖尿病肾病模型。将32只造模成功大鼠随机分为B、C、D、E组,另择8只健康雄性SD大鼠(体质量≤200 g)为A组,A、B组给予10 mg/(kg·d)生理盐水;C、D组分别给予30 mg/(kg·d)、10 mg/(kg·d)青蒿琥酯;E组给予10 mg/(kg·d)依那普利。灌胃给药12周后,观察大鼠24 h尿蛋白定量、血肌酐(Cr)、尿素氮(BUN)、空腹血糖、体质量、肾脏肥大指数(KI)的变化;Western blot法检测肾组织TLR4蛋白的表达;ELISA法检测血清及肾组织IL-8的水平。结果 B、C、D、E组空腹血糖、KI均明显高于A组,体质量明显低于A组;B、C、D、E组24 h尿蛋白、Cr、BUN、肾组织TLR4蛋白表达、血清及肾组织IL-8水平均高于A组,C、D、E组均低于B组,D组高于C组和E组(均P<0.05)。TLR4蛋白与血清IL-8(r=0.969)、肾组织IL-8(r=0.972)、Cr(r=0.944)、BUN(r=0.903)、24 h尿蛋白(r=0.965)均呈正相关(均P<0.05),肾组织IL-8与Cr(r=0.929)、BUN(r=0.940)、24 h尿蛋白(r=0.962)均呈正相关(均P<0.05)。结论青蒿琥酯可能通过下调肾组织TLR4蛋白的表达,减少炎性因子IL-8的释放,减轻DN的炎症反应,一定程度上缓解DN的发展。Objective To investigate effect of artesunate on expressions of Toll-like receotor-4 （TLR4） and interleu？kin-8 （IL-8） in renal tissue of diabetic nephropathy rats. Methods Male SD rats of over 200 g in body weight （n=45） were injected with low dosage streptozotocin and fed with high fat and sucrose diets to establish diabetes nephropathy （DN） model. Among all rats of successful model, thirty-two were randomly selected and divided into four groups （n=8 in each group）, Mod？el group （Group B）, Artesunate at high dose treatment group [30 mg/（kg · d）] （Group C）, Artesunate at low dose treatment group [10 mg/（kg·d）] （Group D）, Enalapril treatment group [10 mg/（kg·d）] （Group E）. Another eight rats without STZ injec？tion whose body weight is under 200 g were assigned as Normal group （Group A）. Then, rats in Group A and B were given the same volume of normal saline [10 mg/（kg·d）] while rats in Group C, D and E were given 30 mg/（kg·d） Artesunate, 10 mg/（kg·d） Artesunate and 10 mg/（kg · d） Enalapril respectively intragastrically for consecutive 12 weeks. Fasting blood glucose, body weight, kidney index, 24-hours proteinuria, serum creatinine （Cr） and blood urea nitrogen （BUN） were measured. Expression level of TLR4 in renal tissue of rats were examined by Western blot;ELISA was used to quantify the concentration of IL-8 in serum and renal tissue of rats. Results Compared with rats in Group A, the levels of Fasting blood glucose, kidney index , 24-hours proteinuria, Cr and BUN as well as the level of TLR4 in kidney, levels of IL-8 in serum and kidney all significant？ly increased in rats in Group B, C, D and E（P〈0.05）. On the other hand, body weight were decreased in rats of Group B, C, D and E compared to rats in Group A（P〈0.05）. The level of TLR4 in kidney, levels of IL-8 in serum and kidney, 24-hours proteinuria, Cr and BUN in rats of Group C, D and E were significantly lower than those in rats of Group B（P〈0.05）. F

关 键 词：青蒿素 糖尿病 肾病 TOLL样受体4 白细胞介素8 炎症反应 青蒿琥酯 

分 类 号：R587.1[医药卫生—内分泌]