土茯苓总黄酮抗单侧输尿管梗阻大鼠肾间质纤维化研究  

The Improving Effect of Smilax glabra Flavonoids on Renal Interstitial Fibrosis in Rats with Unilateral Ureteral Obstruction

作　　者：蔡月琴[1] 陈方明[1] 方明笋[1] 朱科燕[1] 王德军[1] 

机构地区：[1]浙江中医药大学动物实验研究中心/比较医学研究所,杭州310053

出　　处：《浙江中医药大学学报》2017年第12期944-950,共7页Journal of Zhejiang Chinese Medical University

基　　金：浙江省自然科学基金资助项目(LQ14H290004);浙江中医药大学比较医学创新团队资助项目(XTD201301)~~

摘　　要：[目的]研究土茯苓总黄酮(smilax glabra flavonoids,SGF)对单侧输尿管梗阻(unilateral ureteral obstruction,UUO)大鼠肾功能的影响及相关机制。[方法]将60只雄性SD大鼠分出对照组10只,剩余大鼠建立肾间质纤维化(renal interstitial fibrosis,RIF)模型,将造模后大鼠依据体质量分为模型组、SGF低剂量组15mg/(kg·d)、SGF中剂量组30mg/(kg·d)、SGF高剂量组60mg/(kg·d)及厄贝沙坦组10mg/(kg·d),每组10只。各组大鼠均连续灌胃给予对应药物2周。全自动生化仪检测大鼠血清白蛋白(albumin,ALB)、血清尿素氮(blood urea nitrogen,BUN)和血清肌酐(serum creatinine,Scr)的含量,以及24h尿蛋白(urine total protein,U-TP)、尿尿素氮(urine urea nitrogen,UUN)、尿肌酐(creatinine,CREA)的含量,并计算肌酐清除率(creatinine clearance rate,Ccr);HE染色观察肾组织病理变化;Masson染色观察SGF对肾组织纤维化的影响;免疫组化染色观察肾脏转化生长因子-β1(transformation growth factor-β1,TGF-β1)蛋白表达水平的变化。[结果](1)模型组大鼠血清BUN、Scr含量显著高于对照组(P<0.01),ALB含量显著低于对照组(P<0.01),U-TP、UUN、CREA含量也显著高于对照组(P<0.01),Ccr低于对照组(P<0.05);SGF各剂量组、厄贝沙坦组血清BUN、Scr含量均显著低于模型组(P<0.05或0.01),U-TP、UUN、CREA含量显著低于模型组(均P<0.05)。(2)病理学结果显示模型组大鼠肾实质萎缩,肾小管基底膜不规则改变或完整性丧失,肾间质大量炎症细胞浸润和成纤维细胞聚集,肾间质重度纤维化,免疫组化结果显示TGF-β1蛋白表达水平高于对照组,差异有统计学意义(P<0.01);SGF各剂量组、厄贝沙坦组肾脏在肾实质萎缩、肾小管结构毁损、炎细胞浸润、纤维组织增生等方面较模型组均有不同程度地改善,TGF-β1蛋白表达水平低于模型组,差异有统计学意义(P<0.05或0.01)。[结论]SGF能够改善UUO大鼠的肾功能,并能够减轻RIF,可能与下调TGF-β1蛋�[Objective] To investi gate the effect of smilax glabra flavonoids（SGF） on renal function and renal interstitial fibrosis in rats with unilateral ureteral obstruction（UUO）. [Methods] 60 male rats were divided into two groups： control group（10 rats） and model group（50 rats）, Renal interstitial fibrosis model was successfully established by unilateral ureteral obstruction（UUO） in 50 rats. The model rats were divided into five groups： SGF low dose group[15 mg/（kg·d）], middle dose group[30 mg/（kg·d）], high dose group[60 mg/（kg·d）] and irbesartan group[10 mg/（kg·d）] according to their weight, 10 rats in each group. The rats in SGF groups and irbesartan group were administrated with corresponding drug for 2 weeks. Albumin（ALB）, blood urea nitrogen（BUN）and serum creatinine（Scr） in rat serum, total protein（U-TP）, urine urea nitrogen（UUN）, creatinine（CREA） in 24 h urine were detected, and creatinine clearance rate（Ccr） was calculated. The pathological changes of renal tissue and renal tissue fibrosis were observed by HE staining and Masson staining,respectively. Transformation growth factor-β1（TGF-β1） expression was detected by immunohistochemistry.[Results]（1） BUN and Scr in rat serum of model group were significantly increased（P〈0.01）, while ALB were significantly decreased（P〈0.01）. U-TP, UUN and CREA in rat urine of model group were increased significantly（P〈0.01）, while Ccr in rat urine of model group was decreased significantly（P〈0.05）. BUN, Scr in rat serum of SGF treatment groups and irbesartan group were significantly decreased（P〈0.05 or 0.01）, as well as U-TP, UUN and CREA in urine were significantly decreased（P〈0.05）.（2）The pathological results showed renal atrophy, renal tubular basement membrane integrity rules change or loss, inflammatory cell infiltration and fibroblast aggregation in renal interstitial, severe renal interstitial fibrosis. In immunohistochemistry, the mean density of TGF-

关 键 词：SGF 单侧输尿管梗阻大鼠 肾功能 RIF 

分 类 号：R331[医药卫生—人体生理学]