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干细胞因子联合粒细胞集落刺激因子动员骨髓干细胞促进单侧输尿管梗阻大鼠肾脏损伤的修复
  • ISSN号:1001-7097
  • 期刊名称:中华肾脏病杂志
  • 时间:0
  • 页码:711-717
  • 语言:中文
  • 分类:R730.53[医药卫生—肿瘤;医药卫生—临床医学] R693.2[医药卫生—泌尿科学;医药卫生—临床医学;医药卫生—外科学]
  • 作者机构:[1]中南大学湘雅二医院小儿肾脏病研究室湖南省小儿肾脏病临床中心肾脏病学与血液净化学湖南省重点实验室,长沙410011
  • 相关基金:基金项目:国家自然科学基金(30672251);教育部博士学科点专项科研基金(20040533043);湖南省重点学科建设基金
  • 相关项目:胚胎后肾间充质细胞转染uPA基因移植治疗慢性肾脏病的实验研究
中文摘要:

目的研究干细胞因子(SCF)联合粒细胞集落刺激因子(G—CSF)动员单侧输尿管梗阻(UUO)大鼠骨髓干细胞对肾间质中微血管、纤维化程度和肾功能的影响,并探讨其对微血管影响的可能机制。方法128只大鼠按数字随机法分为假手术组(Sham组)、SCF联合G—CSF动员组(SCF—G组)、UUO组、UUO+SCF—G组。于实验第5、14、21、28天每组各随机抽取8只处死,检测Scr、肾间质CD34阳性表达细胞数目和Ⅷ因子阳性表达细胞数目、肾间质纤维化和间质病理损害积分、肾皮质血管内皮生长因子(VEGF)mRNA和血小板反应蛋白1(TSP-1)mRNA的表达。结果(1)UUO组2周时可见到肾间质纤维化伴肾小管周微血管的丢失。(2)UUO+SCF—G组肾间质干细胞归巢数目明显高于UUO组和Sham组(P〈0.05)。(3)UUO+SCF—G组。肾小管周微血管指数减少出现的时间晚于UUO组(P〈0.05)。(4)第14、21、28天UUO+SCF—G组间质化纤维程度和肾小管损伤程度均轻于UUO组(P〈0.05)。(5)UUO+SCF—G组术后VEGFmRNA表达下调出现的时间晚于UUO组,且表达均高于同期UUO组(P〈0.05)。(6)UUO+SCF—G组术后TSP—1mRNA表达增高出现的时间晚于UUO组,且表达均低于同期UUO组(P〈0.05)。(7)在UUO组和UUO+SCF—G组中,肾小管周微血管指数与Scr、间质纤维化积分和肾小管间质病理积分均呈负相关;肾皮质VEGFmRNA表达与肾小管周微血管指数呈正相关;肾皮质TSP-1mRNA表达与肾小管周微血管指数呈负相关。结论(1)UUO大鼠存在肾小管周微血管丢失,并与肾间质纤维化及间质病理损伤相关。(2)联合应用SCF和G—CSF动员骨髓干细胞可以归巢至受损的肾脏,有助于减少肾小管周微血管丢失,并进而减轻肾间质纤维化和间质损害,保护肾功能。(3)联合应用SCF和G—CSF可以上调肾皮质VEGFmRNA水平和下调TSP-1mRNA

英文摘要:

Objective To investigate the effect and possible mechanism of bone marrow stem cell mobilized by stem cell factor (SCF) with granulocyte colony-stimulating factor( G-CSF)on renal peritubular capillary, fibrosis and renal function in unilateral ureteral obstruction (UUO) rats. Methods One hundred and twenty eight healthy male Wistar rats were randomly divided into four groups: Sham group, SCF-G group, UUO group and UUO+SCF-G group. Eight rats of each group were randomly selected and killed on the 5th, 14th, 21st and 28th day. Serum creatinine, CD34 positive cells and factor Ⅷ positive cells in renal interstitium, histopathologic lesion scores of interstitial fibrosis and interstitial pathology in kidney were measured. The mRNA expression of vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) in the renal cortex was detected. Results (1) Tbe renal interstitial fibrosis and the loss of peritubular capillary were observed in UUO group after two weeks. (2) The number of bone marrow stem ceils homing to renal interstitium in UUO +SCF-G group was significantly higher than that in UUO and Sham groups (P〈0.05). (3) The loss of peritubular capillary in UUO+SCF-G group appeared later than that in UUO group (P〈0.05). (4) The interstitial fibrosis and tubule injury was milder in UUO+ SCF-G group than that in UUO group (P〈0.05). (5) The decrease of VEGF mRNA expression of renal cortex in UUO +SCF-G group was seen later than that in UUO group. VEGF mRNA expression in UUO+SCF-G group was higher than that in UUO group. (6) The increase of TSP-1 mRNA expression of renal cortex in UUO+SCF-G group was seen later than that in UUO group. TSP-1 mRNA expression in UUO+SCF-G group was lower than that in UUO group (P〈0.05). (7) In UUO and UUO+SCF-G groups, peritubular capillary index was negatively correlated with serum creatinine, interstitial fibrosis and interstitial lesion scores. VEGF mRNA expression of renal cortex

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期刊信息
  • 《中华肾脏病杂志》
  • 北大核心期刊(2011版)
  • 主管单位:中国科学技术协会
  • 主办单位:中华医学会
  • 主编:
  • 地址:广州市中山二路74号
  • 邮编:510089
  • 邮箱:cmaszb@mail.sysu.edu.cn
  • 电话:020-87331532
  • 国际标准刊号:ISSN:1001-7097
  • 国内统一刊号:ISSN:44-1217/R
  • 邮发代号:46-106
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:26419