藏红花素对氯化锂-匹罗卡品致痫大鼠的脑保护作用及机制研究  

Study on the Brain Protective Effect and Mechanism of Crocin on Lithium Chloride-Pilocarpine-induced Epilepsy in Rats

作　　者：江冉冉 王莉平[2] 李晓东[1] 闫桦[1] JIANG Ran-ran;WANG Li-ping;LI Xiao-dong;YAN Hua(General Hospital of Jizhong energy Fengfeng Group Co.,Ltd.,Handan Hebei 056200,China;Handan Central Hospital,Handan Hebei 056001,China)

机构地区：[1]冀中能源峰峰集团有限公司总医院,河北邯郸056200 [2]邯郸市中心医院,河北邯郸056001

出　　处：《中医药导报》2021年第6期10-14,30,共6页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：河北省医学科学研究课题计划(20201259)。

摘　　要：目的:探讨藏红花素对氯化锂-匹罗卡品(Li-Pc)诱导癫痫(EP)大鼠脑组织的保护作用并探索其机制。方法:将120只雄性SD大鼠按随机数字表法分为正常对照组,模型组,丙戊酸钠组和藏红花素低、中、高剂量组。采用Li-Pc诱导制备EP大鼠模型,注射Pc前30 min,各组分别腹腔注射相应药物。通过Racine评分评估EP发作程度,HE染色法和TUNEL法行大脑海马组织病理学检查和神经元凋亡观察;生化分析法检测海马组织SOD、CAT活力和MDA含量,ELISA法检测TNF-α、IL-1β、IL-6含量;Western blotting法检测海马组织GRP78、CHOP、Cleved Caspase-12、Bcl-2、Bax、NF-κB蛋白表达。结果:与模型组比较,丙戊酸钠组和藏红花素中、高剂量组大鼠EP发作等级降低(P<0.01);海马组织病变和海马神经元凋亡状况明显改善,凋亡指数降低(P<0.01);SOD、CAT活力升高且MDA、TNF-α、IL-1β、IL-6含量降低(P<0.05或P<0.01);GRP78、CHOP、Cleved Caspase-12、Bax、NF-κB表达下调而Bcl-2表达上调(P<0.01),Bcl-2/Bax比值升高(P<0.01)。与丙戊酸钠组比较,藏红花素高剂量组大鼠EP发作等级降低(P<0.01);海马神经元凋亡指数降低(P<0.01);SOD活力升高且MDA、TNF-α、IL-6含量降低(P<0.05或P<0.01);GRP78、CHOP、Cleved Caspase-12、Bax、NF-κB蛋白表达下调而Bcl-2表达上调(P<0.05或P<0.01),Bcl-2/Bax比值升高(P<0.01)。结论:藏红花素对Li-Pc所致EP大鼠脑组织具有保护作用,可能与藏红花素抑制内质网应激通路介导的氧化应激和炎症反应有关。Objective:To explore the protective effect of crocin on the brain tissue of rats with lithium chloride-pilocarpine(Li-Pc)induced epilepsy(EP)and explore its mechanism.Methods:A total of 120 male SD rats were divided into normal control group,model group,sodium valproate group and crocin low,medium and high-dose groups according to the random number table method.The EP rat model was induced by Li-Pc.30 minutes before the injection of Pc,the corresponding drugs were injected intraperitoneally in each group.The seizure degree of EP was evaluated by Racine score.The brain hippocampal histopathology and neuronal apoptosis were observed by HE staining and TUNEL.The activity of SOD,CAT and the content of MDA in hippocampus were detected by biochemical analysis.The content of TNF-α,IL-1βand IL-6 was detected by ELISA.The expression of GRP78,CHOP,Cleved Caspase-12,Bcl-2,Bax,NF-κB protein in hippocampus were detected by Western blotting method.Results:Compared with the model group,the seizure grade of EP in sodium valproate group and crocin medium and high-dose groups was lower(P<0.01).The pathological changes of hippocampal tissue and apoptosis of hippocampal neurons were significantly improved,and the apoptosis index was decreased(P<0.01).The activity of SOD,CAT were increased and the content of MDA,TNF-α,IL-1β,IL-6 were decreased(P<0.05 or P<0.01).The expression of GRP78,CHOP,Cleved Caspase-12,Bax,NF-κB were downregulated,Bcl-2 was up-regulated(P<0.01),and the ratio of Bcl-2/Bax was increased(P<0.01).Compared with sodium valproate group,the degree of EP seizures in crocin high dose group was reduced and the apoptosis index was decreased(P<0.01).The activity of SOD was increased and the content of MDA,TNF-α,IL-6 was decreased(P<0.05 or P<0.01);the expression of GRP78,CHOP,Cleved Caspase-12,NF-κB were down-regulated,Bcl-2 was up-regulated(P<0.05 or P<0.01),and the ratio of Bcl-2/Bax was increased(P<0.01).Conclusion:Crocin has a protective effect on the brain tissue of EP rats induced by Li-Pc,which may be related

关 键 词：癫痫 藏红花素 内质网应激 氧化应激 炎症 大鼠 

分 类 号：R285.5[医药卫生—中药学]