二氟甲基鸟氨酸对糖尿病合并抑郁症大鼠的认知功能障碍及血清代谢组学的调节作用

Effects of difluoromethylornithine on cognitive dysfunction and serum metabolomics in diabetic depression rats

目的:本文旨在研究二氟甲基鸟氨酸对糖尿病合并抑郁症大鼠的认知功能障碍及血清代谢组学的调节作用的影响。方法:将大鼠随机分为5组:对照组(Control)、模型组(Model)、二氟甲基鸟氨酸低剂量组(DFMO 0.1)、二氟甲基鸟氨酸中剂量组(DFMO 0.25)、二氟甲基鸟氨酸高剂量组(DFMO 0.5)进行后续实验。HE染色检测海马神经元病理损伤程度;TUNEL染色检测神经元细胞凋亡;RT-PCR检测Survivin、Caspase-3 mRNA水平及Bcl-2/Bax;试剂盒检测serotonin(5-HT)及metabolite 5-hydroxyindoleacetic(5-HIAA)含量;全自动生化分析仪检测总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇水平(HDL-C);Western blot检测GLT-1、BDNF、AMPKα1、PGC-1α、GLUT4蛋白表达水平。结果:与Model组相比,DFMO 0.25、0.5组病理损伤程度明显改善(P<0.05),凋亡细胞明显减少(P<0.05),Survivin mRNA水平、Bcl-2/Bax显著升高(P<0.05),Caspase-3 mRNA水平显著降低(P<0.05),GLT-1、BDNF蛋白水平显著升高(P<0.05),5-HT、5-HIAA含量显著升高(P<0.05),TC、TG、LDL-C水平显著降低(P<0.05),HDL-C水平显著升高(P<0.05),AMPKα1、PGC-1α、GLUT4蛋白水平显著升高(P<0.05)。结论:二氟甲基鸟氨酸对糖尿病合并抑郁症大鼠具有治疗作用。

Objective:This study was designed to investigate the effects of difluoromethylornithine on cognitive dysfunction and serum metabolomics regulation in diabetic and depressed rats.Methods:Rats were randomly divided into 5 groups:control group,model group,difluoromethylornithine low-dose group(DFMO 0.1),difluoromethylornithyl medium-dose group(DFMO 0.25)and difluoromethylornithyl high-dose group(DFMO 0.5)for follow-up experiments.Pathological damage degree of hippocampal neurons was detected by HE staining.Apoptosis of neuron cells was detected by TUNEL staining.Survivin and Caspase-3 mRNA levels and Bcl-2/Bax were detected by RT-PCR.Test kit detects serotonin(5-HT)and metabolite 5-hydroxyindoleacetic(5-HIAA).Total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)were measured by automatic biochemical analyzer.Protein expression levels of GLT-1,BDNF,AMPK alpha 1,PGC-1a and GLUT4 were detected by Western blot.Results:Compared with model group,degree of pathological damage DFMO 0.25,0.5 group were obviously improved(P<0.05),apoptotic cells decreased significantly(P<0.05),mRNA levels of Survivin,Bcl-2/Bax were significantly higher(P<0.05),Caspase 3 mRNA level decreased significantly(P<0.05),GLT-1,BDNF protein levels were significantly increased(P<0.05),5-HT,5-HIAA content significantly increased(P<0.05),TC,TG,LDL-C levels were significantly decreased(P<0.05),HDL-C levels were significantly increased(P<0.05),AMPKα1,PGC-1α,GLUT4 protein levels were significantly increased(P<0.05).Conclusion:Difluoromethylornithine has therapeutic effect on diabetic depression rats.