1,25- (OH)2D3对大鼠肾纤维化的影响及其机制  

EFFECT OF 1,25-(OH)2D3 ON RENAL FIBROSIS IN RATS AND ITS MECHANISM

作　　者：王佳祺 张令歌 孙明姝[2] 李勋亮 孙建平[1] WANG Jiaqi;ZHANG Lingge;SUN Mingshu;LI Xunliang;SUN Jianping(Department of Nephrology,The Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院肾病科,山东青岛266003 [2]青岛大学附属医院风湿免疫科,山东青岛266003

出　　处：《青岛大学学报（医学版）》2020年第6期640-644,共5页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金资助项目(81871288)。

摘　　要：目的探讨1,25-(OH)2D3是否能通过调节肾脏microRNA-21的表达延缓肾纤维化的进展。方法将SD大鼠随机分为假手术组(Sham组)、单侧(左)输尿管结扎组(UUO组)和1,25-(OH)2D3干预组(干预组),每组12只。UUO组和干预组采用单侧(左)输尿管结扎法建立梗阻性肾纤维化大鼠模型,Sham组仅游离左侧输尿管而不结扎。干预组给予0.06μg/(kg·d)的1,25-(OH)2D3(溶于2 mL花生油)灌胃,持续28 d;Sham组和UUO组均给予等体积花生油灌胃。分别于灌胃14、28 d时,每组取6只大鼠,测定其血肌酐(Scr)、尿素氮(BUN)、钙(Ca)、磷(P)等水平;取左侧肾脏相同部位组织制作病理组织切片,行苏木精-伊红染色和Masson染色,在光镜下观察肾小管间质损伤及纤维化情况;采用RT-PCR法检测各组肾组织microRNA-21的表达水平。结果 UUO组的肾纤维化面积大于干预组和Sham组。UUO组和干预组大鼠各时间点Scr、BUN以及microRNA-21表达水平均高于Sham组,但干预组较UUO组降低,差异均有显著性(F=5.82~280.71,P<0.05)。结论 1,25-(OH)2D3可能通过下调microRNA-21表达,在一定程度上抑制肾纤维化并保护肾功能。ObjectiveTo investigate the possibility of 1,25-(OH)2D 3 delaying the progression of renal fibrosis by regulating the expression of microRNA-21 in the renal tissues.MethodsA total of 36 Sprague-Dawley rats were randomly divided into sham operation group(sham group),left unilateral ureteral obstruction group(UUO group),and 1,25-(OH)2D 3 treatment group(treatment group),with 12 rats in each group.The rats in the UUO group and treatment group underwent left unilateral ureteral obstruction to establish a rat model of obstructive renal fibrosis,while the rats in the sham group had their left ureter only dissociated from the kidney but not ligated.The rats in the treatment group were intragastrically administered 1,25-(OH)2D 3(dissolved in 2 mL peanut oil)at a dose of 0.06μg/(kg·d)for 28 consecutive days;the rats in the sham group and UUO group were given the same volume of peanut oil by intragastric administration.On days 14 and 28 of the intragastric administration,six rats of each group were randomly selected for analysis.The levels of serum creatinine(SCr),blood urea nitrogen(BUN),serum calcium(Ca),serum phosphorus(P)were measured;the renal tissues from the same part of the left kidney were collected to make histopathological sections for hematoxylin-eosin staining and Masson staining,and the pathological changes of renal tubulointerstitial injury and fibrosis were observed under an optical microscope;RT-PCR was employed to measure the expression of microRNA-21 in the renal tissues of the rats in each group.ResultsThe renal tubulointerstitial fibrosis area was significantly larger in the UUO group than in the sham group and treatment group.The UUO group and treatment group had significantly higher SCr and BUN as well as expression of microRNA-21 than the sham group at all time points,but the treatment group had significantly lower indicators listed above compared with the UUO group(F=5.82-280.71,P<0.05).Conclusion1,25-(OH)2D 3 can inhibit the progression of renal fibrosis and protect renal function to a certain e

关 键 词：骨化三醇 微RNAS 肾 纤维化 大鼠 

分 类 号：R692[医药卫生—泌尿科学] R977.24[医药卫生—外科学]