毛蕊花糖苷通过Wnt/β-catenin信号通路对新生大鼠缺血缺氧性脑损伤的改善作用  

Improvement effect of verbascoside on ischemia-hypoxic brain damage in neonatal rats through Wnt/β-catenin signaling pathway

作　　者：徐霞 张艺森 雷瑞瑞 XU Xia;ZHANG Yisen;LEI Ruirui(Department of Neonatology,Zhumadian Central Hospital,Zhumadian 463000,China)

机构地区：[1]驻马店市中心医院新生儿科,驻马店463000

出　　处：《中华中医药杂志》2023年第10期4897-4901,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：河南省医学科技攻关计划项目(No.LHGJ20221058)。

摘　　要：目的:探究毛蕊花糖苷通过调控Wnt/β-连环蛋白(β-catenin)信号通路对缺血缺氧性脑损伤(HIE)新生大鼠的作用。方法:将72只新生SD雄性大鼠随机分为6组:假手术组、模型组、阳性药物组、毛蕊花糖苷高剂量组、毛蕊花糖苷低剂量组、毛蕊花糖苷+通路抑制组,每组12只,按组分别给予相应的干预。神经学评分评估大鼠神经行为学功能;TUNEL细胞凋亡检测试剂盒检测大鼠海马组织细胞凋亡率;干湿重法检测脑组织含水量;采用ELISA检测海马组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)的含量;荧光定量PCR法检测海马组织中Wnt1、Wnt3a、β-catenin mRNA表达水平;Western Blot法检测海马组织中Bcl-2相关x蛋白(Bax)、半胱氨酸蛋白酶-3(Caspase-3)、Wnt1、Wnt3a、β-catenin蛋白的表达水平。结果:与模型组比较,毛蕊花糖苷高剂量组、毛蕊花糖苷低剂量组大鼠神经学评分,脑组织含水量,细胞凋亡率,凋亡相关蛋白Bax、Caspase-3及炎症因子TNF-α、IL-1β含量均显著降低(P<0.05),Wnt1、Wnt3a、β-catenin mRNA及蛋白的表达量显著升高(P<0.05);与毛蕊花糖苷高剂量组比较,毛蕊花糖苷低剂量组、毛蕊花糖苷+通路抑制组大鼠神经学评分、脑组织含水量、细胞凋亡率、凋亡相关蛋白Bax、Caspase-3及炎症因子TNF-α、IL-1β含量均显著升高(P<0.05),Wnt1、Wnt3a、β-catenin mRNA及蛋白的表达量显著降低(P<0.05)。结论:毛蕊花糖苷可通过调控Wnt/β-catenin信号通路,促进相关基因表达,缓解HIE新生大鼠脑损伤。Objective:To explore whether verbascoside can improve HIE neonatal rats by regulating the Wnt/β-catenin signaling pathway.Methods:Seventy-two newborn male SD rats were randomly divided into six groups:sham operation group,model group,positive drug group,high-dose verbascoside group,low-dose verbascoside group,verbascoside+pathway inhibition group,with 12 rats in each group,the corresponding interventions were given by group.The neurological score was used to evaluate the neurobehavioral function of rats;TUNEL cell apoptosis detection kit was used to detect the apoptosis rate of rat hippocampal tissue;dry-wet weight method was used to detect the water content of brain tissue;ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in hippocampal tissue;fluorescence quantitative PCR was used to detect the expression levels of Wnt1,Wnt3a and β-catenin mRNA in hippocampus;Western Blot was used to detect the expression levels of Bcl-2 associated X protein(Bax),cysteine protease-3(Caspase-3),Wnt1,Wnt3a,and β-catenin proteins in hippocampus.Results:Compared with the model group,the neurological score,brain water content,cell apoptosis rate,apoptosis-related proteins Bax,Caspase-3,and inflammatory factors TNF-α and IL-1β in the high-dose verbascoside group,the low-dose verbascoside group were significantly lower(P<0.05),the expression of Wnt1,Wnt3a,β-catenin mRNA and protein was significantly higher(P<0.05);compared with the high-dose verbascoside group,the neurological score,brain water content,cell apoptosis rate,apoptosis-related proteins Bax,Caspase-3,and inflammatory factors TNF-α and IL-1β in the the low-dose verbascoside group and the verbascoside+pathway inhibition group were significantly higher(P<0.05),the expression of Wnt1,Wnt3a,β-catenin mRNA and protein was significantly lower(P<0.05).Conclusion:Verbascoside can promote the expression of related genes and alleviate brain damage in newborn rats with HIE by regulating the Wnt/β-catenin signaling pathway.

关 键 词：毛蕊花糖苷 WNT Β-连环蛋白 缺血缺氧性脑损伤 神经行为学功能 肉苁蓉 

分 类 号：R285.5[医药卫生—中药学]