mTOR在活性维生素D3调控Thy-1肾炎中的靶点作用以及机制的探讨

发布时间：2018-06-19 03:06

本文选题：活性维生素D3 + 系膜细胞　；参考：《石河子大学》2014年硕士论文

【摘要】：目的探讨mTOR和活性维生素D3调控大鼠肾炎过程的相关性以及活性维生素D3的作用靶点。方法将60只健康的雄性SD大鼠随机分为空白对照组（Control Group, CG）、肾炎模型组（NephritisGroup, NG）、肾炎+活性维生素D3干预组(Nephritis+1.25(OH)2D3Group, NVG)、肾炎+活性维生素D3+雷帕霉素干预组((Nephritis+1.25(OH)2D3+Rapamycin Group, NVRG)，每组15只；给予除CG组外的所有大鼠一次性尾静脉注射单克隆抗Thy-1抗体（25μL/100g），诱导系膜细胞增生型肾炎模型，造模成功后给予NVG和NVRG组大鼠活性维生素D30.5μg/(只·d)灌胃，同时给予NVRG组大鼠雷帕霉素1mg/（Kg·d）灌胃，直到第21天实验结束；分别于干预后第1、3、7、14、21天每组随机处死3只大鼠，处死的大鼠前一天均收集24h尿液，检测24h尿蛋白定量，肾组织标本经HE和PAS染色后确定肾脏病理损害分级，免疫组化法检测肾组织中PCNA、mTOR的表达。结果1.NG组大鼠在注射抗Thy-1抗体后第1天即产生大量尿蛋白，第3天达高峰，至第21天恢复正常； NVG组和NVRG组大鼠在各时间点的尿蛋白水平均显著低于NG组（p0.05），且在第14天恢复正常。2.NG组大鼠肾组织在注射抗Thy-1抗体后第3天出现病理学改变，第7天病理损害达高峰，第21天恢复正常；NVG和NVRG组大鼠肾组织病理损害在不同时间点均较NG组减轻，且两组之间无显著差异。3.与CG组相比，NG组PCNA、mTOR的表达明显增强（p0.05）；与NG组相比，NVG组和NVRG组PCNA、mTOR表达明显减少（p0.05），，NVG组和NVRG组PCNA、mTOR的表达无显著差异（p＞0.05）。结论1.活性维生素D3可以显著抑制大鼠肾小球系膜细胞的增殖；2.mTOR参与了活性维生素D3对大鼠肾炎的调控过程，可能是活性维生素D3的作用靶点。
[Abstract]:Objective to investigate the relationship between mTOR and active vitamin D _ 3 in regulating the process of nephritis in rats and the target of active vitamin D _ 3. Methods Sixty healthy male Sprague-Dawley rats were randomly divided into control group, CGN, Nephritis group, NGN, nephritis active vitamin D3 intervention group, nephritis active vitamin D3 group, NVGN group, nephritis active vitamin D3 rapamycin group, NVRGG group, 15 rats in each group. All rats except CG group were given one-off tail vein injection of 25 渭 L / 100 g of monoclonal anti-Thy-1 antibody to induce Mesangial proliferative glomerulonephritis model. The rats in NVG and NVRG groups were given active vitamin D 30.5 渭 g / r (d only). At the same time, NVRG rats were given rapamycin 1 mg / kg d intragastrically until the end of the 21st day, 3 rats in each group were randomly killed on the 21st day after intervention, and 24 hours urine was collected on the day before the rats were killed. The pathological grade of kidney was determined by HE and pas staining and the expression of PCNAmTOR in renal tissue was detected by immunohistochemical method. Results 1. The rats in NG group produced a large amount of urine protein on the first day after injection of anti-Thy-1 antibody, reached the peak on the third day, and returned to normal on the 21st day. The levels of urinary protein in NVG group and NVRG group were significantly lower than those in NG group at each time point, and recovered to normal on the 14th day. 2. The renal tissue of NVG group and NVRG group showed pathological changes on the 3rd day after injection of anti-Thy-1 antibody, and the pathological damage reached the peak on the 7th day. On the 21st day, the pathological damage of renal tissue in NVG and NVRG groups was less than that in NG group at different time points, and there was no significant difference between the two groups. 3. Compared with CG group, the expression of PCNAnmTOR in NG group was significantly higher than that in CG group, and there was no significant difference between NVG group and NVRG group in the expression of PCNAmTOR in NVG group and NVRG group (P > 0.05), but in NVRG group and NVRG group, there was no significant difference in the expression of PCNAmTOR between NVG group and NVRG group (P > 0.05). Conclusion 1. Active vitamin D 3 can significantly inhibit the proliferation of rat Mesangial cells. 2. MTOR participates in the regulation process of active vitamin D 3 on rat nephritis, which may be the target of active vitamin D 3.
【学位授予单位】：石河子大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692.31

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