木瓜苷通过抑制NF-κB P65/TNF-α通路活性减轻小鼠脑缺血再灌注诱导的组织损伤  

Glucosides of chaenomeles speciosa attenuate ischemia/reperfusion-induced brain injury by regulating NF-κB P65/TNF-α in mouse model

作　　者：马竞 何文龙[2] 高重阳[1] 余瑞云 薛鹏 牛永超[3] MA Jing;HE Wenlong;GAO Chongyang;YU Ruiyun;XUE Peng;NIU Yongchao(Department of Neurology, Xinxiang Central Hospital, Xinxiang 453000, Henan Province, China;Department of General Medicine, Xinxiang Central Hospital, Xinxiang 453000, Henan Province, China;Department of Magnetic Resonance, Xinxiang Central Hospital, Xinxiang 453000, Henan Province, China)

机构地区：[1]新乡市中心医院神经内科,河南新乡453000 [2]新乡市中心医院全科医学科,河南新乡453000 [3]新乡市中心医院磁共振室,河南新乡453000

出　　处：《浙江大学学报（医学版）》2019年第3期289-295,共7页Journal of Zhejiang University(Medical Sciences)

基　　金：河南省医学科技攻关计划(201602168)

摘　　要：目的:探究木瓜苷对小鼠脑缺血再灌注诱导的脑组织损伤的治疗作用和机制。方法:选择8周龄健康C57BL/C小鼠50只,分别设置手术对照组、模型对照组、木瓜苷组,其中木瓜苷组按给药剂量不同分别设置木瓜苷30、60、90 mg/kg 组,木瓜苷采用灌胃方式给药。HE染色观察脑组织细胞形态;Zea-Longa 5分评分法评估神经功能;TUNEL染色检测细胞凋亡;ELISA法检测氧化应激和炎症因子水平;蛋白质印迹法检测关键通路分子和神经功能分子。结果:与手术对照组比较,模型对照组小鼠脑组织损伤严重,细胞发生严重凋亡、氧化应激,炎症反应剧烈,炎症和凋亡促进因子NF-κB P65和TNF-α表达水平升高,并伴随神经功能因子髓鞘相关糖蛋白(MAG)和少突胶质细胞髓鞘糖蛋白(OMgp)表达水平下降(均 P < 0.01 )。与模型对照组比较,木瓜苷组小鼠脑组织损伤有所缓解,细胞凋亡改善,氧化应激和炎症反应缓和,炎症和凋亡促进因子NF-κB P65和TNF-α表达水平降低,并伴随神经功能因子MAG和OMgp表达水平升高(均 P <0.01)。其中,木瓜苷剂量为60 mg/kg时效果最好。结论:木瓜苷可以抑制NF-κB P65和TNF-α表达,降低脑组织氧化应激、炎症反应和细胞凋亡,且木瓜苷剂量为60 mg/kg时对小鼠脑缺血再灌注损伤的治疗效果最好。Objective: To investigate the effect and mechanism of glucosides of chaenomeles speciosa (GCS) on ischemia/reperfusion-induced brain injury in mouse model. Methods: Fifty 8-week C57BL/C mice were randomly divided into five groups with 10 in each group: sham group, model group, GCS 30 mg/kg group, GCS 60 mg/kg group and GCS 90 mg/kg group, and the GCS was administrated by gavage (once a day) for 14 d . HE staining was performed to investigate the cell morphology;the Zea-Longa scores were measured for neurological activity;TUNEL staining was performed to investigate the cell apoptosis;ELISA was used to detected the oxidative stress and inflammation;Western Blot was performed to investigate the key pathway and neurological functional molecules. Results: Compared with the sham group, the brain tissues in model group were seriously damaged, presenting severe cell apoptosis, oxidative stress and inflammation, associated with increased NF-κB P65 and TNF-α levels as well as decreased myelin associate glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (OMgp)levels (all P <0.01). Compared with the model group, the brain tissues in GCS groups were ameliorated, and cell apoptosis, oxidative stress and inflammation were inhibited, associated with decreased NF-κB P65 and TNF-α levels as well as increased MAG and OMgp levels (all P <0.01), which were more markedly in GCS 60 mg/kg group. Conclusion: GCS can inhibit the NF-κB P65 and TNF-α, reduce the oxidative stress and inflammation, decrease the cell apoptosis in mouse ischemia/reperfusion-induced brain injury model, and 60 mg/kg GCS may be the optimal dose.

关 键 词：木瓜/化学 皂苷类/药理学 脑缺血/药物疗法 再灌注损伤/药物疗法 细胞凋亡 氧化性应激 炎症 NF-κB/代谢 肿瘤坏死因子α/代谢 

分 类 号：R743[医药卫生—神经病学与精神病学]