摘要
目的研究丹酚酸B对马兜铃酸肾病肾小管间质病变的防治作用机制。方法运用马兜铃酸(aristolochicacid,AA)灌胃造成马兜铃酸肾病模型,将36只大鼠随机分成3组:模型组(n=12),每日接受AA灌胃,剂量为5 mg/(kg.d);治疗组(n=12),每日接受AA灌胃[5 mg/(kg.d)]后随即接受丹酚酸B(salvianolic acid,SalB)灌胃[10 mg/(kg.d)];正常组(n=12),每日接受同体积的生理盐水灌胃。药物处理持续8周。每周称量动物体重以调整用药剂量。第2、4、6、8周收集24 h尿液标本,第8周末麻醉后摘取肾脏做病理检测,采用RT-PCR法测定肾组织基质金属蛋白酶9(MMP-9)、肾组织纤溶酶原激活物抑制物-1(PAI-1)、ITGβ-1、单核细胞趋化因子-1(MCP-1)、基质金属蛋白酶组织抑制物-1(TI MP-1)mRNA的表达。结果模型组较正常组肾间质明显增宽,间质细胞增多,胶原成分显著增加。与模型组比较,治疗组PAI-1、TI MP-1、ITGβ-1 mRNA的表达减弱,MMP-9 mRNA增加。结论自丹参中分离出的SalB对慢性马兜铃酸肾病肾小管间质性损伤有较强的抗纤维化作用。
Objective To study the mechanism of salvianolic acid B in preventing and treating renal tubulointerstitial injury caused by aristolochic acid.Methods Rat model of aristolochic acid nephropathy was induced by intragastric administration of aristolochic acid.Thirty-six rats were randomly divided into model group,treatment group and normal control group.In model group,twelve rats received aristolochic acid [5 mg/(kg·d)] by gastric lavage each day.In treatment group,after gastric lavage of aristolochic acid [5 mg/(kg·d)],the twelve rats received gastric lavage of salvianolic acid B [10 mg/(kg·d)] each day.Gastric lavage of the same volume of saline was given to the 12 rats in normal control group each day.The above-mentioned treatments lasted for 8 weeks.Each week the animals were weighed to adjust the dosage.Overnight urine samples were collected from each rat at week 2,week 4,week 6 and week 8.At the end of week 8,kidneys were removed from each group under anesthesia for pathological measurement.The expressions of MMP-9,PAI-1,ITGβ-1,MCP1 and TIMP-1 mRNA in renal tissues were detected by RT-PCR.Results Compared with normal group,model group had significantly widened renal interstitia and increased mesenchymal cells and collagen composition.Compared with those in model group,the expressions of PAI-1,TIMP-1 and ITGβ-1 mRNA decreased significantly but the expression of MMP-9 mRNA increased in treatment group.Conclusion Salvianolic acid B isolated from Danshen has a strong antifibrotic effect on tubular interstitial injury of chronic aristolochic acid nephropathy.
出处
《西安交通大学学报(医学版)》
CAS
CSCD
北大核心
2010年第6期766-769,共4页
Journal of Xi’an Jiaotong University(Medical Sciences)
基金
国家自然科学基金资助项目(No.30572442)
上海市教育委员会E-研究院建设计划项目资助(No.E03008)
上海市教委高校创新团队项目资助~~
关键词
马兜铃酸肾病
丹酚酸B
抗纤维化
大鼠
aristolochic acid nephropathy
salvianolic acid B
anti-fibrosis
rat