CAJ | 학술논문

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。
목적：관찰청호호지대당뇨병신병（DN）대서모형신조직Toll양수체（TLR）4、백세포개소（IL）-8표체적영향。방법건강웅성SD대서（체질량＞200 g）채용고당고지연합복강주사30 mg/kg련뇨좌균소（STZ）법건립당뇨병신병모형。장32지조모성공대서수궤분위B、C、D、E조，령택8지건강웅성SD대서（체질량≤200 g）위A조， A、B조급여10 mg/(kg·d)생리염수；C、D조분별급여30 mg/(kg·d)、10 mg/(kg·d)청호호지；E조급여10 mg/(kg·d)의나보리。관위급약12주후，관찰대서24 h뇨단백정량、혈기항(Cr)、뇨소담(BUN)、공복혈당、체질량、신장비대지수（KI）적변화；Western blot법검측신조직TLR4단백적표체；ELISA법검측혈청급신조직IL-8적수평。결과 B、C、D、E조공복혈당、KI균명현고우A조，체질량명현저우A조；B、C、D、E조24 h뇨단백、Cr、BUN、신조직TLR4단백표체、혈청급신조직IL-8수평균고우A조，C、D、E조균저우B조，D조고우C조화E조（균P<0.05）。TLR4단백여혈청IL-8（r=0.969）、신조직IL-8（r=0.972）、Cr（r=0.944）、BUN（r=0.903）、24 h뇨단백（r=0.965）균정정상관（균P<0.05），신조직IL-8여Cr（r=0.929）、BUN（r=0.940）、24 h뇨단백（r=0.962）균정정상관（균P<0.05）。결론청호호지가능통과하조신조직TLR4단백적표체，감소염성인자IL-8적석방，감경DN적염증반응，일정정도상완해DN적발전。
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). Furthermore, compared with rats in Group D, the levels of TLR4 in kidney, IL-8 in serum and kidney, 24-hours proteinuria, Cr and BUN were decreased in rats in Group C and E(P<0.05). Pearson correlation analysis showed that the expression lev?el of TLR4 positively correlated with IL-8 level in serum (r=0.969, P<0.05), IL-8 level in kidney (r=0.972, P<0.05), 24-hours proteinuria(r=0.965, P<0.05), Cr(r=0.944, P<0.05)and BUN(r=0.903, P<0.05). IL-8 level in kidney positively correlated with 24-hours proteinuria(r=0.962, P<0.05), Cr(r=0.929, P<0.05)and BUN(r=0.940, P<0.05). Conclu?sion Artesunate decreases expression of TLR4 and IL-8, reduce 24-hours proteinuria, inhibits the inflammation of the DN,relives the pathological lesions of nephron rats with diabetic nephropathy.