摘要
目的观察白藜芦醇联合厄贝沙坦对单侧输尿管梗阻(unilateral ureteral obstruction,UUO)大鼠肾间质纤维化的影响并探讨其可能机制。方法制备UUO肾间质纤维化大鼠模型,将40只大鼠随机分为5组,即假手术组、模型组、白藜芦醇组、厄贝沙坦组以及白藜芦醇和厄贝沙坦联合组,每组8只。术后2周处死大鼠,过碘酸-Schiff染色和脂氢过氧化病理分析肾间质纤维化指数,并应用免疫组织化学方法检测α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA),用Western Blot分析α-SMA、fibronectin、p-Smad3、p NF-κBp65、ICAM-1、TNF-α,用ELISA检测过氧化物酶体增殖剂激活受体(peroxisome proliferators-activated receptors,PPARs)、转化生长因子β1(transforming growth factor-β1,TGF-β1)、巨噬细胞炎症蛋白2(marcophage inflammatory protein-2,MIP-2)和单核细胞趋化因子1(monocyte chemtaticprotein-1,MCP-1)。结果过碘酸-Schiff染色和脂氢过氧化结果显示模型组肾小管损伤面积远大于其它各组。免疫组化分析模型组中α-SMA的表达高于其它各组,联合治疗组α-SMA的表达在治疗组中表达较少,但高于假手术组。模型组大鼠肾间质α-SMA、fibronectin、p-Smad3、p NF-κBp65、ICAM-1、TNF-α的表达增多,联合治疗组较厄贝沙坦和白藜芦醇组的表达减少(P<0.05),但厄贝沙坦和白藜芦醇组之间差异无统计学意义(P>0.05)。模型组TGF-β1、MIP-2和MCP-1的水平高于其它各组,在治疗组中,联合治疗组这些细胞因子的水平低于另外2组。与模型组比较,其它组PPAR(α、β和γ)酶活性增加(P<0.05)。结论白藜芦醇和厄贝沙坦可抑制NF-κB、TGF-β1等途径减缓肾纤维化的病程进展,且联合治疗对肾纤维化的减缓更显著。
Objective This study was designed to examine the protective effects of resveratrol（RSV） in combination withirbesartan（IBS） against renal fibrosis induced by unilateral ureteral obstruction（UUO） and elucidate the potential mechanisminvolved. Methods Rats were randomly divided into five groups,each with 8 rats： sham-operated, UUO, RSV, IBS and RSV/IBS groups. After operation 2 weeks, histological changes were examined using periodic acid-Schiff. α-smooth muscle actin（α-SMA） was measured by immunohistochemistry. α- SMA, fi bronectin, p- Smad3, p NF- κBp65, ICAM- 1 and TNF- α weredetected using western blot. Lipid hydroperoxide and PPAR-α,-β and-γ activity was measured. Transforming growth factor-β1（TGF-β1）,marcophage inflammatory protein-2（MIP-2） and monocyte chemtatic protein-1（MCP-1） were detected usingELISA kits. Results The renal injury including extracellular matrix deposition and tubulointerstitium damage in UUO groupwere significantly higher than the other groups by Periodic acid-Schiff staining and lipid hydroperoxide. α-SMA expression inUUO group was significantly higher than the others using immunohistochemistry, and the expression in RSV or IBS was higherthan that in RES/IBS group. The expression of α-SMA, fibronectin, p-Smad3, p NF-κBp65, ICAM-1 and TNF-α in renalinterstitial tissue from UUO group was higher than that from the others, and these proteins from RES/IBS group was lower thanthat from RSV or IBS group, but no significant difference existed between RES and IBS group（P〉0.05）. The levels of TGF-β1,MIP-2 and MCP-1 from UUO group were higher than the other groups（P〈0.05）, and among therapeutic groups, these cytokinelevels from RSV/IBS group was lower than the other treatment groups. Compared with UUO group, the activity of PPAR α,βand γ in the other groups up-regulated, in particular, sham and RSV/IBS group（P〈0.05）. Conclusions RSV or/ and IBStreatment inhibits NF-κB and TGF-β1 pathway to delay renal interstitial fibrosis, especial
作者
李迎春
郑义
段燕灵
江星
LI Yingchun ZHENG Yi DUAN Yanling JIANG Xing(Department of Paediatrics, Xili People＇s Hospital of Nanshan District, Shenzhen, Guangdong 518000, China)
出处
《中国热带医学》
CAS
2017年第1期41-46,共6页
China Tropical Medicine
基金
深圳市科技创新委员会项目(No.JCYJ20140411095040441)
