摘要
目的:观察阿托伐他汀对大鼠移植肾骨桥蛋白表达的影响。方法:实验于2005-08/12在南京医科大学病理学实验室完成。以封闭群成年近交系Wistar雄性大鼠为供者,SD雄性大鼠为受者,供、受体各35只,体质量250～300g。建立同种异体大鼠肾移植模型,术后将接受肾移植的SD大鼠随机分成3组:环孢素A组、环孢素A+低剂量阿托伐他汀组和环孢素A+高剂量阿托伐他汀组,每组10只。①术后7d,4周分别采血,检测血肌酐,术后4周处死动物取移植肾作病理。比较光镜下BANFF评分。②免疫组化法检测肾组织骨桥蛋白表达并借助图像分析软件比较骨桥蛋白阳性小管百分比。③用印迹杂交法测定各组鼠肾骨桥蛋白mRNA的表达。④计数资料采用χ2检验,计量资料采用t检验,组间均数比较采用Mann-WhitneyU检验。结果:共行大鼠肾移植60次,其中预实验25次,受鼠死亡10只;正式实验35次,受鼠死亡5只,余下的大鼠均存活30d以上,存活率85.7%(30/35)。存活的30只大鼠列入3个观察组。①加用阿托伐他汀组大鼠肾功能显著好于环孢素A组(P<0.05)。②光镜下各组大鼠肾小球结构基本正常,但阿托伐他汀组间质炎细胞浸润和小管炎程度较环孢素A组轻。③免疫组化显示正常肾组织只在Henle袢表达极少量的骨桥蛋白,环孢素A治疗4周后,可见皮质集合管骨桥蛋白表达明显增强,而加用阿托伐他汀治疗组骨桥蛋白表达明显较轻,阿托伐他汀降低骨桥蛋白表达的作用呈剂量依赖性。④印迹杂交法测定移植肾内骨桥蛋白mRNA表达水平显著低于环孢素A组(P<0.01),且与阿托伐他汀剂量呈正相关。结论:阿托伐他汀对大鼠移植肾骨桥蛋白的表达有显著的抑制作用。肾移植患者服用阿托伐他汀可能有助于减轻移植肾间质炎症和移植肾血管病变,降低环孢素肾毒性,延缓慢性移植肾肾病。
AIM： To investigate the effect of atorvastatin on the renal expression of osteopontin in rats＇ kidney allograft model. METHODS： The experiment was conducted in the Laboratory of Pathology of Nanjing Medical University between August and December 2005. Totally 35 inbred male SD rats were ,used as recipients and 35 male Wistar rats as donors. which weighed 250-300 g. Firstly synergistic kidney allograft model was established, thereafter the recipients were randomized into three groups, 10 rats in each group： ciclosporin A group, ciclosporin A plus low-dosage atorvastatin group and ciclosporin A plus high-dosage atorvastatin group. ① Blood was isolated at day 7 and week 4 after operation to measure serum creatiriine. Animals were killed at week 4 after operation to take out kidney： BANFF score was compared under light microscope. ② Osteopontin expression of nephridial tissue was examined with immunohistochemical method, and the percentage of positive tubule of osteopontin was compared with image analysis software. ③Osteopontin mRNA expression was identified with blotting and in situ hybridization. ④Numeration data and measurement data were examined with x^2 test and t test. Inter-group difference was compared with Mann- Whitney U test. RESULTS： Totally 60 kidney transplantation in rats were performedl of which there were 25 preliminary experiments with 10 dead recipients and 35 formal experiments with 5 dead recipients. The other rats lived over 30 days with the survival rate of 85.7% （30/35）, The 30 survival rats were assigned into 3 observational groups. ①The renal function of rats in the ciclosporin A plus low-dosage atorvastatin groupand ciclosporin A plus high-dosage atorvastatin group was obviously better than that in the ciclosporin A group （P 〈 0.05）. ②The structure of renal corpuscle was near to normal in each group under light microscoPe, but the infiltration of inflammatory cells in matrix and inflammatory level of tubule in the ciclosporin A plus low-dosage atorvastatin
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2007年第4期605-609,共5页
Journal of Clinical Rehabilitative Tissue Engineering Research
