mTOR在活性維生素D3調(diào)控Thy-1腎炎中的靶點作用以及機制的探討
本文選題:活性維生素D3 + 系膜細胞; 參考:《石河子大學(xué)》2014年碩士論文
【摘要】:目的探討mTOR和活性維生素D3調(diào)控大鼠腎炎過程的相關(guān)性以及活性維生素D3的作用靶點。 方法將60只健康的雄性SD大鼠隨機分為空白對照組(Control Group, CG)、腎炎模型組(NephritisGroup, NG)、腎炎+活性維生素D3干預(yù)組(Nephritis+1.25(OH)2D3Group, NVG)、腎炎+活性維生素D3+雷帕霉素干預(yù)組((Nephritis+1.25(OH)2D3+Rapamycin Group, NVRG),每組15只;給予除CG組外的所有大鼠一次性尾靜脈注射單克隆抗Thy-1抗體(25μL/100g),誘導(dǎo)系膜細胞增生型腎炎模型,造模成功后給予NVG和NVRG組大鼠活性維生素D30.5μg/(只·d)灌胃,同時給予NVRG組大鼠雷帕霉素1mg/(Kg·d)灌胃,直到第21天實驗結(jié)束;分別于干預(yù)后第1、3、7、14、21天每組隨機處死3只大鼠,處死的大鼠前一天均收集24h尿液,檢測24h尿蛋白定量,腎組織標(biāo)本經(jīng)HE和PAS染色后確定腎臟病理損害分級,免疫組化法檢測腎組織中PCNA、mTOR的表達。 結(jié)果1.NG組大鼠在注射抗Thy-1抗體后第1天即產(chǎn)生大量尿蛋白,第3天達高峰,至第21天恢復(fù)正常; NVG組和NVRG組大鼠在各時間點的尿蛋白水平均顯著低于NG組(p0.05),且在第14天恢復(fù)正常。2.NG組大鼠腎組織在注射抗Thy-1抗體后第3天出現(xiàn)病理學(xué)改變,第7天病理損害達高峰,第21天恢復(fù)正常;NVG和NVRG組大鼠腎組織病理損害在不同時間點均較NG組減輕,且兩組之間無顯著差異。3.與CG組相比,NG組PCNA、mTOR的表達明顯增強(p0.05);與NG組相比,NVG組和NVRG組PCNA、mTOR表達明顯減少(p0.05),,NVG組和NVRG組PCNA、mTOR的表達無顯著差異(p>0.05)。 結(jié)論1.活性維生素D3可以顯著抑制大鼠腎小球系膜細胞的增殖;2.mTOR參與了活性維生素D3對大鼠腎炎的調(diào)控過程,可能是活性維生素D3的作用靶點。
[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.
【學(xué)位授予單位】:石河子大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2014
【分類號】:R692.31
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