IgA肾病大鼠血管免疫炎症病变的保护作用探讨  

Protective effects of leflunomide on IgA nephropathy accompanied by vasculopathy： experiment with rats

作　　者：张建荣[1] 张艳霞[1] 张承英[1] 杨娜[2] 谢生智[3] 

机构地区：[1]中国人民武装警察部队总医院肾内科,北京100039 [2]中国人民武装警察部队总医院南二科 [3]中国人民武装警察部队总医院肿瘤二科

出　　处：《中国急救复苏与灾害医学杂志》2016年第2期136-141,共6页China Journal of Emergency Resuscitation and Disaster Medicine

摘　　要：目的探讨来氟米特及辛伐他汀对IgA肾病血管病变的作用并探讨其可能的机制。方法48只sD大鼠随机分为对照组、模型组、辛伐他汀组、来氟米特组。分别于第4，8，10周时观察大鼠一般情况、24h尿蛋白定量、血生化（甘油三酯（triglyerideTG）、总胆固醇（totalcholesterolTC）、高密度脂蛋白（highdensity lipoprotein HDL、）、低密度脂蛋白（10wdensity lipoproteinLDL）、Ca、肌酐（creatinine Cr）、TP、ALB）及肾脏病理学改变，用免疫组化及RT—PCR的方法检测肾组织中炎症因子单核细胞趋化蛋白-1（monocyte chemoattractant protein-1MCP-1）、血管细胞黏附分子-1vascular cell adhesion molecule-1 VCAM-1）表达的变化。结果第10周时，与对照组、IgAN组相比，模型组大鼠24h尿蛋白定量、G、TC、LDL、Ca、Cr水平均显著升高（P〈0．05）；TP、ALB水平显著降低（P〈0．05）。免疫荧光显示IgA沿肾小球系膜区呈团块状沉积。免疫组化和RT—PCR的结果显示各治疗组MCP-1、VCAM-1的表达均低于模型组（P〈0．05）。与辛伐他汀治疗组相比，来氟米特能明显降低肾脏病理学改变，MCP-1、VCAM-1的表达也明显减少（P〈0．05）。结论来氟米特可通过抑制免疫炎症反应减轻肾血管病变，延缓肾问质纤维化，减少大鼠尿蛋白，发挥肾保护作用。与辛伐他汀相比，来氟米特的肾脏保护作用更强。Objective To investigate the effects of leflunomide and simvastatin on vasculopathy in IgA nephropathy, and explore the possible maehnism thereof. Methods 36 SD rats were made into IgAN models , and then randomly divided into 3 equal groups： model group without further treatment, simvastatin group undergoing intragastric administration of simvastatin at the dosage of 20 mg/kg/d forl0 days, and leflunomide group undergoing intragastric administration of leflunomide at the dosage of 2 mg/kg/d for 10 weeks. Aand another 12 rats underwent intragastric administration of distilled water for 10 weeks （control group）. 4, 8, and 10 weeks after the experimwnt began 24-hour urine samples were colhed from 4 rats from each group to examine the urine protein. Blood sample was collected from the abdominal aorta to examine the total protein （TP）, albumin （ALB）, triglyceride （TC）, total cholesterol （TC）, high density lipoprutein （HDL）, low density lipop[rotein （LDL）, serum calcium, and serum ereatinine （Cr） with automatic biochemistry analyzer. The left kidney was taken out to undergo pathological exaimnation. The mRNA expression and protein expression of monocyte ehemotactie protein 1 （MCP-1） and vascular cell adhesion factor （VCAM-1） were tested by immunohistochemistry and RT-PCR. Results At week 10, the values of TG, TC, LDL, and serum calcium of the model, simvastatin, and leflunomide groups were all significantly lower than those of the control group （all P 〈 0.05）; the TP, TC, LDL, and serum calcium of the simvastatin group were all significantly lower than those of the model group （all P 〈0.05）. The lesion scores of the glomeruli, uriniferous thbules, and renal blood vessels of the simvastatin and leflunomide groups were all significantly lower than those of the model group （all P 〈0.05）.; and the lesion scores of the glomeruli, uriniferous thbules, and renal blood vessels of the simvastatin and leflunomide groups were all lower than those of the model group （al

关 键 词：IGA肾病 血管病变 来氟米特 MCP-1 VCAM-1 

分 类 号：R392[医药卫生—免疫学]