开心解郁丸上调PPARα/FGF21/FGFR1通路改善慢性不可预知温和应激模型大鼠的抑郁样行为  

Kaixin Jieyu Pills Up-Regulated PPARα/FGF21/FGFR1 Pathway to Improve Depression-Like Behavior in Chronic Unpredictable Mild Stress Model Rats

作　　者：翟吴剑文 杨凤梅 金雨静 杨芮 黄世敬[1] 潘菊华[1] 陈宇霞[1] Zhai Wujianwen;Yang Fengmei;Jin Yujing;Yang Rui;Huang Shijing;Pan Juhua;Chen Yuxia(Research and Development Center of Traditional Chinese Medicine,Guanganmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)

机构地区：[1]中国中医科学院广安门医院中药研发中心,北京100053

出　　处：《世界科学技术-中医药现代化》2023年第12期3829-3836,共8页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会面上项目(81573790):基于lncRNA-miRNA网络对神经血管单元稳态调控探讨益气开郁中药抗抑郁机制,负责人:黄世敬;中国中医科学院中央级公益性科研院所基本科研业务费“优势病种-医院制剂-新药”研发专项(ZZ15-XY-LCQ-04):开心解郁颗粒治疗抑郁症的新药临床前研究,负责人:黄世敬;中国中医科学院中央级公益性科研院所基本科研业务费“优势病种-医院制剂-新药”研发专项(ZZ15-XY-PT-17):黄精健脑颗粒治疗轻度认知障碍的医疗机构制剂研究,负责人:潘菊华。

摘　　要：目的探究开心解郁丸(KJP)对抑郁症模型大鼠肝组织过氧化物酶体增殖物激活受体α(PPARα)、血清及海马组织成纤维生长因子21(FGF21)和海马组织成纤维生长因子受体1(FGFR1)的影响。方法通过慢性不可预知温和应激法(CUMS)建立抑郁症大鼠模型,观察抑郁行为学改变;使用酶联免疫吸附法(ELISA)检测血清FGF21含量;免疫组织化学法(IHC)检测海马组织中FGF21和FGFR1的定位、表达变化;使用蛋白免疫印迹法(Western blot)检测海马组织中FGF21、FGFR1和肝脏PPARα蛋白表达水平;实时荧光定量法(RT-qPCT)检测FGF21、FGFR1、PPARα的mRNA表达趋势。结果CUMS模型大鼠PPARα、FGF21、FGFR1的蛋白与mRNA表达水平与正常组相较均显著下降(P<0.001)。KJP可显著改善CUMS模型大鼠抑郁样行为(P<0.001);显著提升血清中FGF21水平(P<0.001);有效提升肝脏PPARα蛋白表达水平(P<0.05),显著改善其mRNA表达水平(P<0.001);明显改善海马组织FGF21、FGFR1的蛋白和mRNA表达水平(P<0.01)。结论PPARα/FGF21/FGFR1通路可能参与了抑郁症发病过程;上调PPARα/FGF21/FGFR1通路可能与KJP抗抑郁机制有关。Objective To explore the effects of Kaixin Jieyu Pill(KJP)on peroxisome proliferator-activated receptor alpha(PPARα),serum and hippocampal tissue fibroblast growth factor 21(FGF21)and hippocampal tissue fibroblast growth factor receptor 1(FGFR1)in rats with depression model.Methods A rat chronic stress model was prepared using the chronic unpredictable mild stimulus method(CUMS)to observe behavioral changes in depression.Hippocampal FGF21,FGFR1 and liver PPARαprotein and mRNA expression levels were measured in hippocampal tissues by western blot and real-time fluorescence quantification(RT-qPCT).Results The expression levels of PPARα,FGF21 and FGFR1′s protein and their mRNA were dramatically decreased in the CUMS model rats compared with the normal group(P<0.001).KJP could modify the depressive-like behaviors of rats(P<0.001),upregulate the protein expression level of PPARα,FGF21,and FGFR1(P<0.05,P<0.01,P<0.01);markedly modify the mRNA expression levels of PPARα,FGF21,and FGFR1(P<0.001,P<0.01,P<0.01).Conclusion PPARα/FGF21/FGFR1 pathway may participate in the pathogenesis of depression;upregulation of PPARα/FGF21/FGFR1 pathway may be related to the antidepressant mechanism of KJP.

关 键 词：开心解郁丸 抑郁症 过氧化物酶体增殖物激活受体Α 成纤维生长因子21 成纤维生长因 子受体1 肝主疏泄 

分 类 号：R285.5[医药卫生—中药学]