慢性马兜铃酸肾病大鼠贫血发生的机制  

Pathogenesis of anemia in chronic aristolochic acid nephropathy rats

作　　者：乔颖进[1] 谌贻璞[1] 芮宏亮[1] 董鸿瑞[1] 刘章锁[2] 

机构地区：[1]卫生部中日友好医院肾病中心,北京100029 [2]郑州大学第一附属医院肾病风湿科

出　　处：《中华肾脏病杂志》2009年第12期925-929,共5页Chinese Journal of Nephrology

基　　金：卫生部属（管）医疗机构临床学科重点项目（2005-2007年度）.

摘　　要：目的探讨慢性马兜铃酸肾病（CAAN）贫血的发生机制。方法用62只SD大鼠筛查血红蛋白（Hb），求正常值。随机选择24只Hb正常的大鼠，分为对照组及模型组，各12只，后者予关木通浸膏水溶液间断灌胃制作CAAN模型。在给药前及8周末，分别检测两组各6只大鼠体质量、Hb、尿蛋白量（24h）及肌酐清除率（Ccr），然后处死大鼠，留取肾组织做Masson染色观察肾间质纤维化程度；实时定量PCR法检测肾组织中红细胞生成素（EPO）mRNA表达；免疫组化染色观察肾组织中I型胶原（ColⅠ）、氨基肽酶P（APP）、低氧诱导因子（HIF）1α及2α的蛋白表达。结果大鼠的正常Hb值为（155.9±16.5）g／L，低于123.6g／L为贫血。给药前，对照组与模型组间各指标的差异均无统计学意义。8周末时，与对照组比较，模型组大鼠Hb和Ccr显著下降[（121.66±15.68）g／L比（169.00±12.89）g／L，（0.63±0.13）ml／min比（1.27±0.18）ml／min]；尿蛋白量（24h）显著增多[（27.04±9.40）mg／d比（6.11±0.84）mg／d]；肾间质纤维化相对面积及ColⅠ相对面积显著增加[（12.89±2.33）％比（0.55±0.10）％，（13.92±2.92）％比（1.32±0.84）％]；肾组织APP蛋白表达和EPOmRNA表达显著下调[（0.55±0.23）％比（3.77±1.06）％，0.005±0.001比0.032±0.013]；HIF-1α和HIF-2α蛋白表达显著上调（2.55±0.16比1.12±0.46，2.33±0.33比1.15±0.27）（均P〈0.01）。结论CAAN的贫血发生可能与肾小管周毛细血管毁坏所导致的EPO产生减少有关，虽然HIF表达已代偿性增强，但仍未能阻止贫血发生。Objective To study nephropathy （CAAN） rats. Methods the pathogenesis of anemia in chronic aristolochic acid The hemoglobin （Hb） values of sixty-two male SD rats were assayed to determine its normal range. Among them, 24 rats with normal Hb value were randomly divided into 2 groups： model group （MG） in which rats received the extract of Aristolochia manshuriensis Kom （AmK） by gavage, and control group （CG）received tap water only by garage. Body weight （BW）, Hb, 24 h urinary protein excretion （UP） and ereatinine clearance （Ccr） of 6 rats in each group were measured before administration and at the end of the 8th week, respectively, then these rats were sacrificed. The relative area of renal interstitial fibrosis was measured by microscopy. The mRNA expression of erythropoietin （EPO） in kidney tissue was determined by real-time RT-PCR; protein expression of type Ⅰ collagen （Col Ⅰ）, aminopeptidase P （APP）, hypoxia inducible factor 1α and 2α（HIF-1α and HIF-2α in kidney tissue was examined by imnmnohistochemistry staining. Results Hb values of normal rats presented normal distribution. The nnrmal Hb was （155.9±16.5） g/L. Rat anemia was diagnosed when HI） was below 123.6 g/L. There was no difference in all the examination results between CG anti MG betbre adminislration （P〉0.05）. Compared with CG, the Hb and Ccr in MG were significantly decreased [（121.66±15.68） g/L vs （169.00±12.89） g/L, （0.63±0.13） ml/min vs （1.27±0.18） ml/min, P〈 0.01], and the UP in MG was significantly increased at the end of the 8th week [ （27.04±9.40） mg/d vs （6.11±0.84） rag/d, P〈0.01]; the relative areas of fibrosis and Col I in renal interstitium of MG were significantly enlarged [（12.89±2.33）% vs （0.55±0.10）%, （13.92±2.92）% vs （1.32±0.84）%, P〈 0.01]; the protein expression of APP and the mRNA expression of EPO in the kidney tissue of MG were significantly down-regulated [（0.25±0.23）% vs （3.77±1.06）%, 0.005±0.0

关 键 词：马兜铃酸 贫血 红细胞生成素 肾小管周围毛细血管 低氧诱导因子 

分 类 号：R692.9[医药卫生—泌尿科学] R556[医药卫生—外科学]