文章摘要
罗后宙,于永刚,张慧明,万有华,刘东荣,廖松柏,刘为池,武英杰.转录因子GATA-3在单侧大鼠肾脏梗阻模型中的表达[J].南京医科大学学报,2009,29(1):74~80
转录因子GATA-3在单侧大鼠肾脏梗阻模型中的表达
Insights into the role of the transcription factor GATA in the signal transduction pathway of renal fibrosis
投稿时间:2008-08-08  
DOI:10.7655
中文关键词: 转录因子  GATA-3  肾脏纤维化
英文关键词: transcription factor  GATA-3  renal intersititial fibrosis
基金项目:
作者单位
罗后宙 解放军181医院泌尿外科,广西 桂林 541002 
于永刚 解放军181医院泌尿外科,广西 桂林 541002 
张慧明 解放军181医院泌尿外科,广西 桂林 541002 
万有华 解放军181医院病理科,广西 桂林 541002 
刘东荣 解放军181医院泌尿外科,广西 桂林 541002 
廖松柏 解放军181医院泌尿外科,广西 桂林 541002 
刘为池 解放军181医院泌尿外科,广西 桂林 541002 
武英杰 解放军181医院泌尿外科,广西 桂林 541002 
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中文摘要:
      目的:通过动物实验模型观察转录因子GATA-3在肾脏纤维化中的作用,通过对肾脏纤维化信号通路的干预,进一步了解逆转纤维化进程的策略方向?方法:将54只雄性SPF级Wistar大鼠随机分为单侧输尿管梗阻组(unilateral ureteral obstruction group,UUO)和正常对照组,单侧输尿管梗阻组按照处理因素再分为GATA-3 反义寡核苷酸组(antisense oligonucleotide group,AS),GATA-3 无意义寡核苷酸组(nonsense oligonucleotide group,NS)和生理盐水组,每组9只?正常对照组27只大鼠采取同样的分组方法?分别在试验第1?7?14天处死每小组3只大鼠,HE 和Masson染色观察肾脏纤维化的病理变化并评估纤维化程度,免疫组化方法观察GATA-3? Smad7等阳性表达情况并统计面积?RT-PCR法观察大鼠肾脏组织GATA-3及Smad7 mRNA 表达同时计算灰度值?结果: GATA-3反义寡核苷酸处理的大鼠无论是在梗阻组及正常对照组的肾脏纤维化现象均较其他两个处理组轻微,免疫组化结果显示,在梗阻组及正常对照组组均有GATA-3的表达,通过RT-PCR进一步证实,在梗阻组大鼠的肾脏组织中均有GATA-3及Smad7 RNA 的表达,反义寡核苷酸处理的大鼠Smad7的表达无论是在梗阻组还是正常对照组中均随梗阻时间的延长显著下降?结论:转录因子GATA-3通过减少BMP-7诱导的Smad7的表达,使Smad7阻断转化生长因子(TGF)-β的信号转导作用削弱,加剧了肾脏纤维化的发生发展,进一步证实通过对纤维化信号通路中的转录因子进行干预影响纤维化的进程是可行的?
英文摘要:
      Objective:Through the animal experiment model to observe the action of transcription factor GATA-3 in renal fibrosis,and through interfere in the signal iteral of renal fibrosis to get the deeper message of strategy and direction for reversal renal fibrosis. Methods:Thirty-six male specified-pathogens free Wistar rats were randomly divided into two groups:the unilateral ureteral obstruction group and normal comparison group. The unilateral ureteral obstruction group according to the management agent was subdivided into three group:GATA-3 antisense oligonucleotide group(AS),GATA-3 nonsense oligonucleotide group(NS) and sodium chloride group. The nomal comparison group also adopt the same method divided into three groups. And at the time of study 1?7?14 d executed two rat of each subgroup. Histological changes of renal tubular interstitium were observed by HE and Masson staining. Iminunohistochemistry was performed on renal tissue for observe the expression of GATA-3? Smad7 and so on at each time point. RT-PCR to observe the expression of GATA-3?Smad7 mRNA in renal fibrosis and calculate gray scale. Results:Regardless of ureteral obstruction group and nomal comparison group ,the rat treated with GATA-3 antisense oligonucleotide observed that renal fibrosis little than other two treatment. Iminunohistochemistry observed that transcription factor GATA-3 expression in ureteral obstruction group and nomal group,RT-PCR further infirm that result. At Ureteral Obstruction group detect the expression of GATA-3 and Smad7 RNA;treated with GATA-3 antisense oligonucleotide observed that Smad7 expression in ureteral obstruction group and nomal comparison group even less than the other two treatment. Conclusion:Transcription factor GATA-3 through reduced the expression of Smad7 induced by BMP-7,and impaired the Smad7’s function blockade TGF-β signal transduction, to intensify the renal fibrosis generate and development,further infirmed that interfere in the transcription factor of renal fibrosis signal path to effect the fibrosis’s proceeding was feasible.
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