天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (10): 1112-1115.doi: 10.11958/j.issn.0253-9896.2015.10.007

• 实验研究 • 上一篇    下一篇

1,25(OH)2D3对Thy-1肾炎模型大鼠Ki67、mTOR表达的影响

  

  1. 1新疆石河子大学医学院(邮编832000）； 2新疆石河子大学医学院病理教研室； 3新疆石河子大学医学院第一附属医院肾病科
  • 收稿日期:2015-03-10 修回日期:2015-05-23 出版日期:2015-10-15 发布日期:2015-10-22

Effect of 1,25-dihydroxyvitamin D3 influence on expressions of Ki67 and mTOR in Thy-1#br# nephritis model of rat

  1. 1 College of Medicine, Shihezi University, Xinjiang 832000,China; 2 Department of Pathology ,School of Medicine,
    Shihezi University ;3 Department of Nephrology,the First Affiliated Hospital,School of Medicine ,Shihezi University
  • Received:2015-03-10 Revised:2015-05-23 Published:2015-10-15 Online:2015-10-22

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摘要：

摘要:目的 研究 1,25-二羟基维生素 D3 [1,25(OH)2D3]对 Thy-1 肾炎模型大鼠 Ki67 和哺乳动物雷帕霉素靶蛋白
(mTOR)表达的影响， 并探讨其机制。方法 90 只清洁级雄性 SD 大鼠随机分为对照组、 模型组、 1,25(OH)2D3组， 每组
30 只。模型组与 1,25(OH)2D3组尾静脉注射抗 Thy-1 单克隆抗体建立肾炎模型， 对照组给予等剂量生理盐水。建模
后， 1,25(OH)2D3组给予 1,25(OH)2D3 0.5 μg/d 灌胃， 连续给药 21 d， 对照组及模型组给予等体积花生油。分别于给药
后第 1、 3、 7、 14、 21 天每组随机处死 6 只大鼠， 处死前 1 d 收集 24 h 尿液进行 24 h 尿蛋白定量； 取各组肾组织标本，
经 HE 和 PAS 染色后进行肾脏病理损害评分， 免疫组化法检测肾组织中 Ki67、 mTOR 表达。结果 模型组和 1,25
(OH)2D3组大鼠在建模后第 1 天尿蛋白水平升高， 模型组第 3 天达高峰， 至第 14 天恢复至正常水平， 1,25(OH)2D3组大
鼠第 1、 3、 7 天的尿蛋白水平均低于模型组 （P < 0.05）。1,25(OH)2D3组大鼠肾组织病理损害程度第 3、 7 天较模型组减
轻（P < 0.05）， Ki67、 mTOR 蛋白表达水平较模型组降低（P < 0.05）。24 h 尿蛋白定量， Ki67 表达水平， mTOR 表达水
平及肾组织病理损害评分彼此间均呈正相关。结论 1,25(OH)2D3可抑制 Thy-1 肾炎模型大鼠肾小球系膜细胞的增
殖， 其作用机制可能与减少 Ki67、 mTOR 的表达有关。

关键词: 维生素 D, 蛋白尿, 哺乳动物雷帕霉素靶蛋白, Ki67, 1,25(OH)2D3, Thy-1 肾炎

Abstract:

Abstract： Objective To study the expressions of Ki67 and mTOR in Thy-1 nephritis model of rat who were given
1
,25-dihydroxyvitamin D3[1,25(OH)2D3] and to explore its mechanism. Methods Healthy male SD rats (n=90) were random⁃
ly divided into three groups: control group, model group, 1,25(OH)2D3 treatment group (n=30 in each group). Model group
and 1,25(OH)2D3 treatment group were intravenously injected with anti-Thy1 monoclonal antibody once via tail vein while
the control group were administrated with same volume of normal saline through the same route. 1,25(OH)2D3 were adminis⁃
trated at 0.5 μg per day intra-gastrically for consecutive 21 days in 1,25(OH)2D3 treatment group while equal volume of pea⁃
nut oil were given in control group and model group. Six rats were randomly selected from each group and sacrificed at the
1st , 3rd , 7th , 14th and 21st after drug intervention. Twenty four hour urine sample were collected in each rat just before it was
culled to detect 24-hour urinary protein excretion. Renal tissue samples were harvested and stained with hematoxylin & eo⁃
sin (H&E) and PAS to determine the renal pathological variation and the expressions of mTOR and Ki67 were assessed by
immunohistochemistry. Results Urine protein begin to be detected at the first day after model was established, peaked at
the 3rd days then started dropping until the 14th day when urine sample turned to normal. Urine protein levels were lower in 1,
25(OH)2D3 treatment group at the 1st,3rd,7th day after model establishment than those in model group(P < 0.05). Compared with
model group, the pathological damage of renal tissue in 1,25(OH)2D3 treatment group were alleviated at the 3rd and 7th day after
model establishment (P < 0.05). Expressions of Ki67 and mTOR in 1, 25(OH)2D3 treatment group were reduced compared
with those in model group (P < 0.05). Twenty four hour urinary protein and expressions of Ki67 and mTOR as well as renal
pathological damage were all positively correlated with each other. Conclusion 1,25(OH)2D3 can inhibit the proliferation of
glomerular mesangial cells in Thy-1 nephritis model of rat. And its therapeutic mechanism may be associated with down reg⁃ulating expressions of Ki67 and mTOR.

Key words: vitamin D, proteinuria, mTOR, Ki67, 1,25(OH)2D3, Thy-1 nephritis