全反式维甲酸对阿霉素肾病小鼠肾脏保护作用研究

Reno-protective effect of all-trans retinoic acid on adriamycin-induced nephropathic mice

摘要:

目的：探讨全反式维甲酸（All-trans retinoic acid，ATRA）对阿霉素肾病模型小鼠的肾脏保护作用。方法：将30只BALB/c小鼠，随机分为正常组、阿霉素肾病模型组（模型组）和阿霉素肾病ATRA治疗组（ATRA治疗组），分别腹腔注射给药至10周。免疫组化分析肾脏凋亡蛋白 Fas抗原及Fas抗原配体（Fas ligand，FasL）的表达水平，Real-time PCR技术检测肾脏Fas抗原、FasL的 mRNA表达。结果：模型组与对照组比较，尿蛋白、血脂总胆固醇[（Total cholesterin，TC），（3.09±0.89） mmol/L]、甘油三酯[（Triglyceride，TG），（1.33±0.29） mmol/L]水平明显升高（P值均小于0.05）；ATRA治疗组与模型组比较TC、TG分别为[（1.27±0.31） mmol/L、（1.12±0.45） mmol/L]明显降低（P均小于<0.05）。免疫组化分析：模型组与正常组比较， Fas抗原、FasL表达增加，分别为（650.141 6±153.997 0）、（350.190 7±204.220 6），且差异有统计学意义（P<0.05），治疗组与模型组比较，Fas抗原、FasL表达减少，且差异有统计学意义（P<0.05）。Real-time PCR分析，模型组与正常组相比较，肾组织的 Fas抗原、FasL的表达明显升高，分别为（2.953 7±1.558 1）、（3.680 6±0.273 1）（P<0.05）；ATRA治疗组与模型组相比较 Fas抗原、FasL明显增强，分别为（0.601 3±0.249 9）、（0.729 9±0.730 4）（P<0.05）。结论：ATRA可能通过降低肾脏 Fas抗原、FasL的表达而对肾脏起到保护作用。

Abstract:

Objective：To investigate the reno-protective effect of all-trans retinoic acid（ATRA） on adriamycin（ADR）-induced nephropathic mice. Methods：BALB/c mice were randomly divided into normal group，ADR-induced nephropathic group（model group）and ADR-induced nephropathy treated group（ATRA treatment group）. After ADR-induced nephropathy model was established in model and ATRA treatment group，intraperitoneal injection in normal and model group and ATRA treatment group was performed till the 10th week. Expression of Fas antigen and Fas ligand（FasL） was measured by immunohistochemistry and their mRNA expressions were detected by Real-time PCR. Results：Urinary protein excretion，serum total cholesterin（（TC），（3.09±0.89） mmol/L） and triglyc－eride（（TG），（1.33±0.29） mmol/L） were obviously increased in model group compared with those in normal group（all P<0.05）. TC and TG were （（1.27±0.31） mmol/L and （1.12±0.45） mmol/L） in ATRA treatment group，obviously increased compared with those in model group（all P<0.05）. Immunohistochemistry showed that expression levels of Fas antigen and FasL were （650.141 6±153.996 0） and （350.190 7±204.220 6） in model group，obviously higher than those in normal group，P<0.05. Expression levels of Fas antigen and FasL were decreased in ATRA treatment group，compared with those in model group，P<0.05. Real-time PCR analysis showed that mRNA expression levels of Fas antigen and FasL in model group were （0.601 3±0.249 9） and （0.729 9±0.730 4），significant－ly high than those in ATRA treatment group（both P<0.05）. Conclusion：ATRA can protect kidney damage through decreasing the expression of Fas and FasL.