SnoN蛋白在慢性同种移植肾病大鼠肾组织中的表达及作用 |
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引用本文: | 贾宁,王汉,刘耿容,张桦,周文英.SnoN蛋白在慢性同种移植肾病大鼠肾组织中的表达及作用[J].中国中西医结合肾病杂志,2011,12(2):103-107,189. |
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作者姓名: | 贾宁 王汉 刘耿容 张桦 周文英 |
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作者单位: | 1. 中山大学附属第五医院肾内科,珠海,519000 2. 中山大学附属第五医d院神经外科,珠海,519000 |
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基金项目: | 广东省科技厅科技计划项目 |
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摘 要: | 目的:观察Smad核转录共抑因子(SnoN蛋白)在慢性移植肾病(CAN)大鼠肾组织的表达及其与CAN大鼠肾脏功能改变、病理学改变、Smad泛素化调节因子2(Smurf2)之间的关系,探讨SnoN蛋白在CAN中的作用。方法:实验组采用近交系大鼠的同种异基因动物间的左肾原位移植,雄性F344大鼠40只为供体,雄性LEW大鼠40只为受体,移植手术后第10天行右肾切除术,对照组采用单肾切除术的雄性大鼠25只。分别于4周、8周、12周、16周及24周处死大鼠,做肾功能、移植肾组织学检测,并借助免疫组织化学与免疫印迹、逆转录-多聚酶联反应方法检测肾组织中snoN蛋白、snoNmRNA的表达;免疫组织化学与免疫印迹方法检测肾组织smurf2的表达,免疫印迹方法检测肾组织p-smad2/3蛋白的表达水平,逆转录-多聚酶联反应方法检测肾组织TGF-β1mRNA的表达。结果:移植组大鼠尿蛋白定量、血清肌酐水平于移植后16周时显著增高,24周时更为显著。snoN蛋白在移植组逐渐降低,24周时降至最低,为对照组的13%。snoNmRNA在移植组和对照组差异无统计学意义;p-smad2/3、smurf2在移植后随疾病进展逐渐升高,24周时达高峰。免疫组织化学结果显示snoN蛋白表达部位、表达时相与smurf2是一致的。相关分析显示,肾移植大鼠snoN蛋白表达水平与24h尿蛋白定量、血清肌酐水平、肾间质纤维化程度呈负相关(P〈0.05,P〈0.01)。与smad2/3、smurf2水平呈显著负相关(P〈0.01)。结论:SnoN蛋白表达下调在CAN发病机制中起作用,同时Smurf2介导SnoN蛋白降解可能参与了这个过程。
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关 键 词: | 慢性移植肾病 SnoN Smurf2 |
Expression and Role of SnoNprotein on Chronic Allograft Nephropathy |
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Institution: | JIA Ning,WANG Han,LIU Gengrong,et al The Fifth Affiliated Hospital,Sun Yet-Sen University,Zhuhai(519000) |
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Abstract: | Objective:To investigate expression and role of co-repressor snoN,smad ubiquitination regulatory factor 2(smurf2)on the rat kidney of chronic allograft nephropathy(CAN)model.Methods:The kidney of Fisher(F344)rats were orthotopically transplanted into Lewis recipients.Animals were harvested respectively at 4weeks,8weeks,12weeks,16weeks,24weeks after transplantation for renal fuction and histologycal examination.The expression of snoN was determinated with RT-PCR、Western-blot and immunohistolchemistry assay,while expression of smurf2 was determined by immunohistochemistry and Western-blot.The expression of TGF-β1 was determinated with RT-PCR and the expression of smad2/3 was determined by Western-blot.Results:The expression of snoNprotein was decreased on allograft,while smurf2 protein was increased and the peak of two was at week24 after transplantation,snoN protein expression loss 13% at 24weeks compared with control groups.The expression of snoNmRNA was no difference between experimental groups and control groups.The expression of decreasd snoNprotein were negative correlated with 24-hour urine protein extent、serum creatinine levels in CAN rats,while negative-correlation with smad2/3 in CAN rats.There was also a significant negative-correlation between snoNprotein and smurf2 in CAN rats after transplantation.Conclusion:The decreased of snoNprotein might play a role and through smurf2 dependent degradtion in the mechanism of CAN. |
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Keywords: | SnoN Smurf2 |
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