益肾化瘀方对肾间质纤维化大鼠肾组织基质金属蛋白酶1及其抑制剂表达的影响  

Impact of Yishen Huayu Decoction (益肾化瘀方) on the Expressions of Matrix Metalloproteinase-1 and Its Inhibitor in Renal Tissue of Renal Interstitial Fibrosis Rats

作　　者：张琳琪[1] 朱建光[2] 汪青[1] 高志卿[1] 刘红亮[1] 王娇[3] 

机构地区：[1]河南中医药大学第一附属医院 [2]河南中医药大学 [3]河南省中医药研究院

出　　处：《中医杂志》2016年第15期1332-1336,共5页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81373612)

摘　　要：目的探讨益肾化瘀方治疗肾间质纤维化的可能作用机制。方法将126只SD大鼠随机分为假手术组、模型组、缬沙坦组及益肾化瘀方高、中、低剂量组,每组21只。除假手术组外各组采用单侧输尿管结扎法制备肾间质纤维化模型,于造模后次日假手术组、模型组予生理盐水20 ml/(kg·d),益肾化瘀方高、中、低各剂量组分别予益肾化瘀方浓缩液32、16、8 g/(kg·d),缬沙坦组予缬沙坦胶囊溶液13.3 mg/(kg·d),每天灌胃1次,共给药28天。分别于术后第7、14、28天(每个时间点取材7只)光镜下观察肾间质病理改变并进行肾间质纤维化评分,检测大鼠肾组织中基质金属蛋白酶1(MMP-1)mRNA、基质金属蛋白酶组织抑制剂1(TIMP-1)mRNA的表达。结果光镜下HE和Masson染色显示,模型组大鼠造模7天后各组大鼠即出现肾间质水肿,间质内炎症细胞呈灶性浸润,至28天大量肾小管萎缩或消失,纤维化程度呈进展性加重。各治疗组肾间质炎细胞浸润数量减少,纤维化程度较模型组均有不同程度的减轻,益肾化瘀方高剂量组与缬沙坦组的病理改变相当。与假手术组同时间点比较,其余各组大鼠在第14、28天时肾间质纤维化评分及肾组织中MMP-1mRNA、TIMP-1mRNA表达均明显升高(P<0.05或P<0.01);与模型组同时间点比较,益肾化瘀方高、中、低剂量组和缬沙坦组大鼠在第14、28天时肾间质纤维化评分明显降低,益肾化瘀方高剂量组在第28天时MMP-1mRNA表达继续增加,而在第7、14、28天时TIMP-1mRNA表达明显降低(P<0.05或P<0.01)。结论益肾化瘀方可能通过抑制肾组织TIMP-1的表达,纠正MMP-1/TIMP-1失衡,从而显示出拮抗肾间质纤维化的作用。Objective To explore the possible mechanism of Yishen Huayu Decoction（ 益肾化瘀方） in treating renal interstitial fibrosis（ RIF）. Methods Totally 126 SD rats were randomly divided into sham operation group,model group,valsartan group,high,medium and low dose Yishen Huayu Decoction group,with 21 rats in each group. Rats in other groups were established RIF models by unilateral ureter ligation method except the sham operation group. From the second day of modeling,the sham operation group and the model group were given normal saline20 ml /（ kg·d）. The high,medium and low dose Yishen Huayu Decoction groups were given Yishen Huayu Decoction in concentration 32,16 and 8 g /（ kg·d） respectively. The valsartan group was given valsartan capsule solution 13. 3mg /（ kg·d）,gavaged once every day,for 28 days. On the 7th,14 th and 28 th day after operation（ 7 rats were examined at each time point）,pathological changes of renal interstitial were examined under optic microscope. Renal interstitial fibrosis was scored. The expressions of matrix metalloproteinase-1（ MMP-1） mRNA and tissue inhibitor matrix metalloproteinase-1（ TIMP-1） mRNA in rats＇ nephridial tissue were detected. Results Under optic microscope,HE stain and Masson stain showed that 7 days after modelling,rats showed renal interstitial edema. Interstitial inflammatory corpuscles showed focal infiltration. A large number of renal tubular atrophied or disappeard until the28 th day. The fibrosis degree showed progressive aggravation. Inflammatory corpuscles infiltration reduced in all treated groups. The fibrosis degree in the treated groups relieved by varying degrees compared with that in the model group.The pathological changes in the high dose Yishen Huayu Decoction group were similar to those in the valsartan group.Compared with the sham operation group at the same time point,the RIF scores and the expressions of MMP-1mRNA and TIMP-1mRNA in nephridial tissue of rats in other groups all increased on the 14 th and 28 th day

关 键 词：肾间质纤维化 益肾化瘀方 基质金属蛋白酶 基质金属蛋白酶组织抑制剂 

分 类 号：R285.5[医药卫生—中药学]