虫草菌丝对慢性肾功能衰竭大鼠微炎症反应的影响  

Effect of Cordyceps mycelia on microinflammation in chronic renal failure rats

作　　者：吴涛[1] 高蕾[1] 李学刚[1] 黄芳芳[1] 宋燕[1] 关广聚[1] 

机构地区：[1]山东大学第二医院肾内科,山东济南250033

出　　处：《中国药理学与毒理学杂志》2010年第4期274-279,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：山东省优秀中青年科学家奖励基金计划(2007BS03059);山东中医药科技发展计划项目(2007-138)~~

摘　　要：目的考察慢性肾功能衰竭(CRF)模型大鼠肾脏组织NF-κB-p65与血清C反应蛋白(CRP)和白细胞介素6(IL-6)浓度的关系,并探讨虫草菌丝对NF-κB表达的抑制作用及其用于治疗微炎症反应的可能性。方法 50只雄性Wistar大鼠随机分为假手术组、模型组、四氢化吡咯二硫代氨基甲酸酯(PDTC)阳性对照组、虫草菌丝3和6g·kg-1治疗组。建模前1d各组大鼠尾静脉抽血,并留取24h尿液,第2天假手术组行假手术,其余4组切除右肾上、下两极约70%肾脏;10d后假手术组再次进行"假手术",其余4组再经左腹壁切除左肾,制备5/6肾切除CRF大鼠模型。建模2周后,PDTC组隔日ip给予PDTC0.01g·kg-1,虫草菌丝治疗组分别ig给予虫草菌丝3和6g·kg-1,每天1次,共12周;假手术组和模型组ig给予等体积生理盐水;给药12周后各组留取血样和24h尿液,处死大鼠取肾。ELISA法检测血清CRP和IL-6浓度,全自动生化仪检测血清肌酐浓度,考马斯亮蓝法测定24h尿蛋白,实时荧光定量RT-PCR法和免疫组织化学法检测肾组织NF-κB-p65mRNA和蛋白表达。结果①建模前,各组大鼠24h尿蛋白和血清肌酐浓度无明显差异;建模14周后,模型组、PDTC组、虫草菌丝3和6g·kg-1组24h尿蛋白和血清肌酐浓度较建模前均明显升高(P<0.01),模型组较假手术组亦明显升高(P<0.01);模型组大鼠肾组织均出现肾小球球囊粘连、局灶节段性硬化及肾小管灶状萎缩和代偿性肥大等CRF病理改变;给药12周后,PDTC组、虫草菌丝3和6g·kg-1组大鼠肾组织病理变化与模型组比较无明显改善,虫草菌丝3和6g·kg-1组24h尿蛋白和血清肌酐浓度明显降低(P<0.01)。②给药12周后,模型组与假手术组比较,血清CRP和IL-6浓度及肾组织NF-κB-p65mRNA和蛋白表达均明显升高(P<0.01),PDTC组、虫草菌丝3和6g·kg-1组与模型组比较均明显降低(P<0.01),虫草菌丝6g·kg-1组比3g·kg-1组降低更为明显(P<0.05)。③各组肾组织NF-κB-p65mRNA表达与�OBJCETIVE To investigate the relationship between NF-kappaB(NF-κB) of renal tissue,levels of C-reactive protein(CRP) and interleukin-6(IL-6) in serum of chronic renal failure(CRF) model rats,and to research effect of Cordyceps mycelia(CM) on NF-κB-p65 and microinflammation in CRF rats.METHODS Fifty male Wistar rats were randomly divided into sham,model,pyrrolidine dithiocarbamate(PDTC),CM 3 and 6 g·kg-1 groups.The rats in sham group were sham-operated,and those in the other four groups had 70% of their right kidneys removed and 10 d later their left kidneys were picked off.Two weeks after the first operation,rats in PDTC group were ip given PDTC 0.01 g·kg-1 every other day,and those in CM 3 and 6 g·kg-1 groups were ig given CM once daily,for 12 weeks.The rats in sham and model groups were ip given normal saline.The blood sample and 24 h urine were reserved before nephrectomy and 14 weeks after nephrectomy.Fourteen weeks after nephrectomy,all the rats were sacrificed and serum CRP and IL-6 concentration was examined by ELISA;serum creatinine(Cr) content and 24 h urinary protein were examined by automatic chemistry analyzer;the expression of NF-κB-p65 mRNA and protein was examined by real-time fluorescent RT-PCR and immunohistochemistry staining,respectively.RESULTS ①Before operation,there was no difference in 24 h urinary protein and Cr between each group.Fourteen weeks after nephrectomy,24 h urinary protein and Cr of model,PDTC,CM 3 and 6 g·kg-1 groups significantly increased.There was also significant increase in model group compared with sham group(P <0.01).Fourteen weeks after nephrectomy,pathological changes of CRF occurred in renal tissue of model group rats.For example,part of glomerulus in nephridial tissue had sacculus adhesion and focal segmental glomerulosclerosis;renal tubes had focal atrophy and protein casts;and renal interstitium had slight fibrosis.After 12 weeks’ medication,the pathological changes in renal tissue of PDTC,CM 3 and 6 g·kg-1 groups did improve compared with model group.M

关 键 词：模型 动物 肾功能衰竭 虫草菌丝 NF-ΚB C反应蛋白 白细胞介素6 

分 类 号：R285[医药卫生—中药学]