马兜铃酸致肾小管周围毛细血管丢失的体内实验研究  

Aristolochic acid induces peritubular capillary loss in mice

作　　者：刘圆圆[1] 李艺[1] 王帅[2] 官涛[1] 郑科[1] 黄云剑[1] 

机构地区：[1]第三军医大学新桥医院肾内科,重庆400037 [2]成都军区总医院肾内科,成都610083

出　　处：《第三军医大学学报》2014年第6期553-557,共5页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81370821);重庆市自然科学基金重点项目(CSTC2013jjB10023)~~

摘　　要：目的观察小鼠马兜铃酸肾病(aristolochic acid nephropathy,AAN)肾小管周围毛细血管(peritubular capillary,PTC)丢失与肾小管损伤、增殖修复的关系。方法 40只C57雄性小鼠按随机数字表法分为对照组及马兜铃酸组(AA组)。AA组小鼠连续腹腔注射马兜铃酸溶液5 mg/(kg·d),对照组注射同体积磷酸盐缓冲液。分别于7、9 d后留取血、尿和肾组织标本。主要检测肾小管损伤积分、PTC丢失量(CD34组化染色)和肾小管增殖(PCNA组化染色)在肾皮质、皮髓交界和髓质的变化,并对三者进行相关性分析。结果与对照组比较,7、9 d AA组小鼠肾小管损伤积分(2.02±0.81)、(2.82±1.31)、PTC丢失量(22.47±20.62)、(40.00±23.50)及PCNA表达量(3.31±2.14)、(1.30±1.07)均显著增加(P<0.01),其中肾小管损伤积分和PTC丢失量9 d组高于7 d组,且两组均在肾皮质处最高,皮髓交界处次之,髓质处最低;相反,肾小管PCNA阳性细胞数9 d组低于7 d组,且两组皮质阳性细胞数均低于皮髓交界。相关分析显示PTC丢失量与肾小管损伤呈正相关,与肾小管PCNA表达量呈负相关,其中皮质处相关性最高(P<0.05)。结论 PTC损伤与AAN肾小管上皮细胞持续损伤和修复不良高度相关,PTC丢失可能是AAN进展的关键因素。Objective To investigate the relationship between peritubular capillary （PTC） loss and tubule injury, proliferation and repair in aristolochic acid-induced nephropathy mice. Methods Forty male C57BL/6J mice were randomly divided into two groups, a control group and an AA group （n = 10）. The AA group was intraperitoneally injected with aristolochic acid （AA） dissolved in phosphate-buffered saline at a dose of 5 mg/kg per day for up to 7 or 9 d, while the control group received saline injection only. Blood, urine and kidneys of ten mice in each group were collected for tubular injury evaluation using a semi-quantitative scale, quantification of peritubular capillary loss （ CD34 immunohistochemistry staining） and proliferation （ PCNA immunohistochemistry staining） of tubule principally. Furthermore, the correlations between PTC loss and both of tubular injury and proliferation in the cortex, cortex-medulla junction and medulla of kidney were analyzed. Results The tubule injury score [2.02 ± 0.81 （7 d）, 2.82 ± 1.31 （9 d） ], PTC loss [22.47 ± 20.62 （7 d）, 40.00 ± 23.50 （9 d）] and positive expression of PCNA [3.31 ± 2.14 （7 d）, 1.30 ± 1.07 （9 d）] of the AA group were significantly higher than those of the control group. Moreover, the tubule injury score and PTC loss were maximum in the cortex, less higher in the cortex-medulla junction and minimum in the medulla. The positive expression of PCNA of day 9 group was significantly less than that of day 7 group. The PCNA- positive cells in the cortex of day 7 group and day 9 group were both less than those in the cortex-medulla junction. PTC loss was correlated with the lesion of tubule （positively） and the expression level of PCNA （neg-atively） in the cortex and cortex-medulla junction, with a more predominant correlation in the cortex than in the cortex-medulla junction. Conclusion The damage of PTC is significantly correlated with progressive lesion of tubule and inhibition of remodeling in aristolochic acid nephr

关 键 词：马兜铃酸 肾小管周围毛细血管 肾小管损伤修复 

分 类 号：R284.1[医药卫生—中药学] R363[医药卫生—中医学]