全反式维甲酸对阿霉素肾病模型小鼠的肾脏保护作用研究

发布时间：2018-06-18 02:42

本文选题：全反式维甲酸 + 凋亡　；参考：《重庆医科大学》2012年硕士论文

【摘要】：目的：探讨全反式维甲酸对阿霉素肾病模型小鼠肾脏保护作用及其可能的作用机制。方法：6-8周龄的雄性BALB/C小鼠随机分为正常组、阿霉素肾病组（模型组）和全反式维甲酸治疗组（治疗组）。一次性尾静脉注射阿霉素10.5mg/kg体重，建立阿霉素肾病小鼠模型。自阿霉素肾病模型建立成功后2W开始，ATRA治疗组给予20mg/kg/次的ATRA腹腔注射（3次/周），ATRA溶解在玉米油中；正常组、模型组腹腔注射给予等次、等量玉米油（3次/周），干预至10W。各组分别于注射阿霉素后第6、10周末处死6只小鼠，通过免疫组织化学方法检测小鼠肾脏Fas、FasL的表达水平；Real-time PCR法检测小鼠肾组织Fas和FasL以及全反式维甲酸受体RARa、RXRa的mRNA的表达水平。结果：与模型组相比，正常组、治疗组尿蛋白水平、血脂胆固醇（TC）、甘油三酯（TG）水平明显降低，差异有统计学意义(P0.05)，血清白蛋白（ALB）的水平明显升高，差异有统计学意义（P0.05）。免疫组化结果显示Fas、FasL的表达量，与模型组相比，正常组和治疗组阳性表达明显减少，差异有统计学意义（P0.05）；荧光定量PCR显示，，与模型组相比，正常组和治疗组的Fas、FasL mRNA的表达量明显减低，差异显著有统计学意义（P0.01）。第10周全反式维甲酸受体RARa、RXRa的mRNA的表达水平，治疗组与正常组相和模型组相比表达明显增加，差异有统计学意义（P＜0.05）。结论：ATRA可以明显减轻阿霉素肾病模型小鼠的肾脏损伤，降低的蛋白尿水平，降低血清TG、TC的水平，这可能是与其拮抗肾脏固有细胞的凋亡蛋白Fas、FasL有关。
[Abstract]:Aim: to investigate the protective effect of all trans retinoic acid on kidney of adriamycin nephropathy model mice and its possible mechanism. Methods male BALB / R / C mice aged 6-8 weeks were randomly divided into normal group, adriamycin nephropathy group (model group) and all-trans retinoic acid treatment group (treatment group). The model of adriamycin nephropathy in mice was established by single tail vein injection of adriamycin 10.5mg/kg. Two weeks after the adriamycin nephropathy model was established, the 20mg/kg/ treatment group was given intraperitoneal injection of 20mg/kg/ three times per week to dissolve in corn oil, while in the normal group, the model group was given the same intraperitoneal injection of the same amount of corn oil three times a week, and the intervention lasted for 10 wt. Six mice were killed at the end of the 6th week after injection of adriamycin. The expression of FasL in kidney was detected by immunohistochemical method and the mRNA expression of FAS, FasL and RARARARARXRa were detected by Real-time PCR. Results: compared with the model group, the levels of urinary protein, serum lipids, cholesterol, triglyceride and TGwere significantly decreased in the normal group and treatment group, and the difference was statistically significant (P 0.05), and the level of serum albumin (ALB) was significantly increased (P 0.05). The results of immunohistochemistry showed that the positive expression of Fas-FasL in normal group and treatment group decreased significantly compared with the model group, and the difference was statistically significant (P0.05A), the fluorescence quantitative PCR showed that compared with the model group, the positive expression of Fas-FasL was significantly lower than that of the model group. The expression of Fas-FasL mRNA in normal group and treatment group was significantly lower than that in control group (P 0.01). At the 10th week, the expression of RXRa mRNA in all trans retinoic acid receptors was significantly increased in the treatment group compared with the normal group and the model group (P < 0.05). Conclusion 1: ATRA can significantly reduce renal injury, decrease the level of proteinuria and decrease the level of serum TGTc in the model mice with adriamycin nephropathy, which may be related to the antagonism of Fas-FasL, the apoptotic protein of renal inherent cells.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R-332;R692.9

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