摘要
目的动态观察黄芪(AM)对单侧输尿管梗阻(UUO)所致肾小管间质纤维化大鼠肝细胞生长因子(HGF)和转化生长因子β1(TGF-β1)表达的影响。方法54只SD大鼠随机分为假手术组、模型组和模型+黄芪治疗组。在造模后第3、7和14天处死动物,观察肾脏病理改变。采用免疫组化方法检测肾组织中TGF-β1、HGF表达。用实时荧光定量RT-PCR检测大鼠HGF mRNA和TGF-β1mRNA表达量。用Western blot检测大鼠HGF和TGF-β1蛋白表达量。结果与假手术组相比,各时间点的模型组大鼠肾脏病理损害进行性加重,黄芪治疗后可明显减轻模型组大鼠的肾小管损伤及肾间质纤维化程度(P<0.05)。随着梗阻时间的延长,模型组大鼠肾组织TGF-β1表达逐渐增加;HGF表达呈现先升高后下降的表达规律,在UUO术后第7天达高峰,此后大幅回落;与模型组各对应时间点比较,黄芪治疗后可使肾组织中的HGF表达显著增高,TGF-β1表达明显降低(P<0.05)。结论黄芪可能通过诱导HGF表达上调及抑制TGF-β1表达,减轻肾间质纤维化。
Objective To study the effect of Astragalus mongholicus（AM） on renal interstitial fibrosis caused by unilateral ureteral obstruction（UUO） in rats in order to elucidate the mechanisms underlying the renoprotective effects of AM.Methods 54 Sprague-Dawley rats were randomly divided into 3 groups：sham-operation group（Sham）,the UUO group（UUO） and UUO ＋ AM group（AM）.The rats were treated at the doses of 10g/（kg·d） AM for 3,7 and 14 days,the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections.The expressions of transforming growth factor-β1（TGF-β1）and hepatocyte growth factor（HGF） were measured by immunohistochemistry staining sections.The mRNA of HGF and TGF-β1 were reverse transcribed and quantified by real-time PCR.The expressions of HGF and TGF-β1 protein were assessed by Western blot.Results Renal damages were exacerbated and the expressions of TGF-β_1 were significantly increased in UUO group in comparison with those of Sham group（P〈0.05）at each time point.HGF expression increased initially and peaked at the day of 7 after UUO and then decreased greatly.The tubular impairment and interstitial fibrosis were alleviated,up-regulations of expressions of TGF-β1 were significantly suppressed,while expressions of HGF were significantly increased in UUO＋AM group in comparison with UUO group（P〈0.05）.Conclusion AM could ameliorate renal interstitial fibrosis induced by UUO in rats.The mechanisms of antifibrotic effects of AM may be associated with up-regulation of HGF expression and down-regulation of TGF-β1 expression in renal intersitial progress.
出处
《卫生研究》
CAS
CSCD
北大核心
2008年第5期566-570,共5页
Journal of Hygiene Research
关键词
黄芪
肾间质纤维化
肝细胞生长因子
转化生长因子Β1
Astragalus mongholicus,renal interstitial fibrosis,hepatocyte growth factor,transforming growth factor-β1
