摘要
目的:观察鲤鱼汤对多柔比星肾损害大鼠的肾保护作用。方法:50只Wistar雄性大鼠随机分为正常组(A组)、模型组(B组)、鲤鱼高(C组)、低(D组)剂量组、厄贝沙坦组(E组)。尾静脉一次性注射多柔比星6.2mg/kg建模。造模后14d灌胃相应药物干预。HE、Masson染色观察肾脏病变,免疫组化检测肾组织成纤维细胞特异性蛋白-1(S100A4)、Smad7、转化生长因子β1(TGF-β1)及胶原蛋白Ⅰ(Col-Ⅰ)的表达。结果:与B组相比,C组大鼠12h尿蛋白浓度(12h-Upc)、尿素氮(BUN)、血清肌酐(SCr)、肾组织TGF-β1、S100A4、Col-Ⅰ、肾小球硬化指数(GSI)及间质损伤指数(TII)降低(P<0.05),血清总蛋白(TP)、白蛋白(Alb)、12h尿量(12h-Uv)及肾组织Smad7升高(P<0.05),除12h-Upc及12h-Uv外,上述指标C组D组E组间无差异。S100A4表达与Col-Ⅰ、GSI及间质胶原沉积呈正相关(P<0.01),与Smad7呈负相关(P<0.01)。结论:鲤鱼汤利尿消肿、拮抗纤维化保护肾脏;上调Smad7负反馈调节TGF-β1/Smad信号转导、抑制EMT及ECM可能是其作用机制之一。
Objective： To study the renal protective effect and mechanism of Cyprinus Carpio Decoction （CCD） on the nephmpathy （ADRN） rats induced by adriamycin. Methods： 50 male Wistar rats were randomly divided into control group （A）, ADRN model group （B）, high CCD group （C）, low CCD group （D） and Irbesartan group （E）. ADRN model rat was established by single caudal vein injection of adriamycin （ADR） 6.2mg/kg. At the 14th day after ADR injection vehicle, the treatment started. The kidney pathological changes were observed under light microscopes by Masson＇s trichrome stained and Hematoxylin- eosin stained. The expression of fibroblast-specific protein 1 （S100A4）, Smad7, transforming growth factorβ1 （TGF-β1） and collagen I （Col I ） were examined by Immunohistochernistry. Results： Compared with group B, level of 12 hours of urine protein concentration （12h-Upc）, bloold urea nitrogen （BUN）, serum creatinine （SCr）, expression of TGF-β1, Col I and S100A4, glomemlosclerosis index （GSI） and interstitial injury index （TII） decreased obviously （P〈0.05）. Expect for 12h-Uv and 12h-Upc, there was no significant difference about the aboved parameters among group C, D and E. Immunohistochemistry Semiquantitative analysis showed that a significant positive correlation existed between the expression of S100A4, Col- I, GSI and interstitial collagen index （P〈0.01）, and a reverse correlation between S 100A4 and Smad7 （P〈0.01）. Conclusion： CCD had protective effectson ADRN via induce diuresis to reduce edema and anti-fibrosis, and one of the mechanisms might involve in the up-regulation of Smad7 expression, subsequently negative regulation of TGF-β1/Smad signaling transduction and suppression of EMT and ECM.
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2013年第6期1855-1859,共5页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金资助项目(No.81072754
No.81072398)
山东省中医药科技发展计划项目(No.2009-176)
山东省科技发展计划(No.2009GG10002044)~~
关键词
鲤鱼汤
多柔比星肾损害
肾纤维化
TGF-β
1
SMAD信号通路
上皮细胞间充质转分化
细胞外
基质沉积
Cypriuns Carpio Decoction
Adriamycin nephropathy
Renal fibrosis
Transforming growth factor-β1/ Smad signaling pathway
Epithelial to mesenchymal transition （EMT）
Extracellular matrix （ECM） deposition
