肾络宁对IgA肾病大鼠肾小管间质损害的实验研究

目的：探讨IgA肾病大鼠肾小管间质损害及中药复方肾络宁的干预作用。方法：SD大鼠随机分为正常组、模型组、肾络宁组、肾炎康复片组。采用牛血清白蛋白和葡萄球菌肠毒素B复合感染的方法建立大鼠IgA肾病模型；实验共16周，药物干预后常规检测尿红细胞、尿蛋白、血尿素氮、肌酐、尿NAG酶，以及免疫荧光观察肾组织病理；原住杂交，免疫组化及计算机图像分析系统观察大鼠肾小管间质损害的病理变化，以及Ⅲ型胶原（Col-Ⅲ）、转化生长因子β1（TGF-β1）、纤溶酶原激活物抑制剂-1（PAI-1）、基质金属蛋白酶-1（MMP-1）、基质金属蛋白酶组织抑制剂-1（TIMP-1）的表达情况。结果：模型组出现肾小管上皮细胞变性，线粒体结构消失，数量减少，间质成纤维细胞增生及胶原纤维形成；尿红细胞、尿蛋白、NAG酶、血肌酐、尿素氮明显增高，Col—Ⅲ、TGF-β1、PAI-1、TIMP-1表达明显增高，MMP-1表达明显降低。肾络宁及肾炎康复片组小管间质损害明显减轻；血尿、蛋白尿、血肌酐、尿素氮、尿NAG明显降低，Col—Ⅲ、TGF-β1、PAI—1、TIMP—1表达明显降低，MMP—1表达明显升高。结论：肾络宁可明显减轻IgA肾病大鼠肾小管间质损害，改善肾功能，延缓间质纤维化及肾衰竭的进程。

Experimental Study on Effect of Shenluoning (SHLN) on IgAN Model Rat Tubulointerstitial Lesions

Objective： To explore the tubulointerstitial lesions of experimental IgA nephrosis （IgAN） model rat, and to observe the curative effect of compound Shenluoning （SHLN） on it .Methods：Sprague-Dawley rats were randomly divided into 4 groups： blank group,IgAN model group, SHLN group and Shenyankangfupian （SYKFP） group. The IgAN rat model was established by injecting steophylococcus enterotoxin B into rat caudal vein, feeding bovine serum albumin.Rats were saerificed at week 16 to detect blood unine nitrogen （BUN）,serum creatinine （Scr）, urine ctythrocyte, 24 hours urine protein excretion （UPE） and urine D- N- Aeetyl glucosaminidase （NAG）. The renal tissues were studied by light microsoopy, electron microsoopy and immunofluorescent examination. In situ hybridizafien（ISH）, imand computer image analysis were used to investigate the pathological change of tubulcintersfitial lesion, and to the expression of collagen Ⅲ（ Col - Ⅲ ）. transforming growth factor - β1 （ TGF -β1 ）,plasminogen activator inhibitor - 1 （PAI - 1）, matrix metalloproteinase（MMP- 1） ,tissue inhibitor of metalloproteinase- 1（TIMP- 1）. Remits.（1） Model group. Degeneration in renal epithelial cells necrosis; mitochondrion structure disappear and quantity decrease; renal Interstitial fibroblasts proliferation and collagen fiber deposition; the content of urine erythrocyte, urine protein, BUN, SCr and NAG devated significantly; the expression of Col- Ⅲ ,TGF-Ⅲ,PAI- 1,TIMP- 1 increased rearkably; the expression of MMP- 1 reduced. （2） SHLN group and SHYKFP groap： The rots＇ tubulonterstitial lesions markedly decreased; content of urine erythrocyte, urine proton, BUN, Scr and NAG are much lower than those of model group; the expression of Col- Ⅲ ,TGF- β1 ,PAI- 1,TIMP- 1decreased evidently; the expression of MMP- 1 increased remrkably. Conclusion：SHLN can observably alleviate tubulointerstitial pathologic injury of IgAN model rats; ameliorate renal function;stayed progression of r