福辛普利联合氯沙坦对单侧输尿管梗阻大鼠肾脏肝细胞生长因子表达的影响  

Effect of Monopril and Losartan on the expression of HGF in rat kidney after unilateral ureteral obstruction

作　　者：宋洁[1] 刘章锁[1] 

机构地区：[1]郑州大学第一附属医院肾内科

出　　处：《郑州大学学报（医学版）》2004年第6期960-963,共4页Journal of Zhengzhou University(Medical Sciences)

基　　金：河南省科技攻关基金资助项目 3 2 44 10 0 84;河南省自然科学基金资助项目 0 4110 40 3 0 0

摘　　要：目的 :观察福辛普利联合氯沙坦对单侧输尿管梗阻 (UUO)大鼠肾脏肝细胞生长因子 (HGF)表达的影响 ,探讨其对肾间质纤维化的保护作用机制。方法 :雌性SD大鼠 30只 ,随机均分为 5组 ,分别为C组 (假手术组 ) ,UUO组 (手术组 ) ,UUO +ACEI组 (福辛普利干预组 ) ,UUO +ARB组 (氯沙坦干预组 ) ,UUO +ACEI+ARB组 (福辛普利联合氯沙坦干预组 )。药物干预组分别于术前 1d及术后给予福辛普利 (10mg·kg-1·d-1) ,氯沙坦 (5 0mg·kg-1·d-1) ,福辛普利联合氯沙坦 (剂量同前 )混悬液灌胃 ,假手术组及手术组每d灌胃同体积生理盐水。各组动物分别在术后第 14d应用鼠尾血压计测量收缩压再处死并收集 3ml血标本及处死前 2 4h尿液 ,留取右侧肾脏。 2 4h尿送检尿肌酐、尿蛋白 ,血标本送检肌酐。光镜下观察肾皮质、间质细胞增生及纤维化改变。用免疫组化方法检测术后第 14d梗阻侧肾脏HGF、转化生长因子 (TGF - β1)、增殖细胞核抗原 (PCNA)表达的改变。结果 :①血压及生化检查 :与假手术组相比 ,UUO组及各药物干预组大鼠收缩压、肌酐清除率、2 4h尿蛋白定量均无明显变化 (P >0 .0 5 )。②大鼠肾组织的病理学改变 :与假手术组相比 ,HE及Masson染色均显示UUO 14d间质增宽 ,肾小管上皮细胞萎缩 ,管腔扩张 ,弥漫的单核。Aim: To investigate the effect of Monopril and Losartan on the expression of HGF in kidney of rat after unilateral ureteral obstruction (UUO) and find out their protective effect on renal interstitial fibrosis. Methods: A total of 30 female SD rats were randomly assigned into five groups: C group(sham-operated group,n=6), UUO group (operation group,n=6), UUO+ ACEI group (Monopril 10 mg·kg -1·d -1 treatment after UUO,n=6), UUO+ARB group (Losartan 50 mg·kg -1·d -1 treatment after UUO,n=6) and UUO+ ACEI +ARB group (combined treatment with the same dose of Monopril and Losartan after UUO,n=6). Obstructed kidneys were removed 14 days after operation. Systolic blood pressure was measured using the tail-cuff method .The samples of blood and the urine of 24 hours were collected to detect the concentration of serum creatinine,the quantity of urinary protein and creatinine.HE and Masson staining were performed, the obstructed kidneys of all rats were immunostained with the specific antibodies of HGF,TGF-β 1,and PCNA. Results:①There were no significant difference of the blood pressure, the quantity of urinary protein of 24 hours and the clearance of creatinine of rats among all of groups;②The range of expansion interstitium in UUO group increased significantly compared to that of sham operation group(P<0.05).③Comparison to sham operation group,the expression of HGF,TGF-β 1 ,PCNA of UUO and treatment groups significantly increased (P<0.05).Comparison to UUO group, Monopril and Losartan significantly increased the expression of HGF,and decreased TGF-β 1,PCNA(P<0.05). Conclusion: Monopril and Losartan may play a protective role in the kidney by increasing the expression of HGF,downregulating TGF-β 1 and alleviating renal interstitial fibrosis after UUO.

关 键 词：梗阻性肾病 肝细胞生长因子 福辛普利 氯沙坦 

分 类 号：R639[医药卫生—外科学]