摘要
目的探讨内皮型一氧化氮合酶(endothelial nitric oxide synthase,e NOS)和一氧化氮(nitric oxide,NO)在单侧输尿管梗阻(unilateral ureteral obstruction,UUO)肾间质纤维化小鼠微血管病变中的作用及机制。方法64只KM小鼠随机分为两组:假手术组n=32只;单侧输尿管梗阻UUO组n=32只。观察4周,每周检测各组小鼠血BUN、Scr及一氧化氮,流式细胞计数外周血CD133+/VEGFR+内皮祖细胞(endothelial progenitor cells,EPCs)、Masson染色观察肾组织形态学变化,免疫组化法检测肾间质CD34+表达计数微血管密度,实时定量PCR检测肾皮质e NOS、VEGF mRNA表达。结果 UUO组血一氧化氮、内皮祖细胞计数、肾间质微血管密度、e NOS、VEGF mRNA表达水平持续下降,在第2、3、4周与对照组差异有统计学意义。一氧化氮水平与肾间质微血管密度呈正相关(r=0.715,P<0.05);e NOS mRNA表达水平与肾间质微血管密度(r=0.624,P<0.05)、内皮祖细胞计数(r=0.375,P<0.05)、VEGF mRNA(r=0.351,P<0.05)呈正相关。结论 e NOS/NO途径参与了UUO小鼠肾间质微血管的调节,其调节涉及对血管舒张功能影响、介导促血管肾脏因子VEGF mRNA表达及动员内皮祖细胞等机制。
Objective To investigate the role of eNOS/NO signaling pathway in peritubular capillary lesions of mouse renal interstitial fibrosis with unilateral ureteral obstruction （ UUC） and the potential mechanism .Methods Sixty-four healthy male KM mice were randomly divided into sham operated group （ n=32 ） and unilateral ureteral obstruction group （n =32）.At each week, serum BUN, Scr and NO were determined and the percentages of CD 133 ＋/VEGFR＋en-dothelial progenitor cells in peripheral blood mononuclear cells were detected by flow cytometry .Morphological changes of the renal tissue were observed using Masson staining .The expression of CD34 ＋cells in the renal interstitium was analyzed by immunohistochemistry to calculate the peritubular capillary density .The expressions of eNos and VEGF mRNA were de-termined by real-time PCR.Results The expression of blood NO , the percentages of endothelial progenitor cells , peritu-bular capillaries, eNOS mRNA, and VEGF mRNA in the UUO group were significantly decreased compared with those of the sham group at 2, 3, and 4 weeks （P〈0.05）.NO was positively correlated with peritubular capillaries （r =0.715, P〈0.05）, eNOS mRNA was positively correlated with peritubular capillaries （r =0.624, P〈0.05）, endothelial progeni-tor cells （r =0.375, P〈0.05）, and VEGF mRNA （r =0.351, P〈0.05）.Conclusions eNOS/NO signaling path-way participates in regulation of peritubular capillary lesions in renal interstitial fibrosis of UUO mice .The mechanism may be partly related to the regulation of vasomotor reflex , the expression of VEGF mRNA and mobilization of endothelial pro-genitor cells.
出处
《中国实验动物学报》
CAS
CSCD
北大核心
2015年第5期484-489,共6页
Acta Laboratorium Animalis Scientia Sinica
基金
福建省卫生厅青年科研课题(编号:2010-2-92)
关键词
内皮型一氧化氮合酶
一氧化氮
肾小管周围微血管
内皮祖细胞
血管生长因子
小鼠
Endothelial nitric oxide synthase
Nitric oxide
Peritubular capillary
Endothelial progenitor cells
Angiogenesis growth factor
Mice
