机构地区:[1]河南中医药大学第一附属医院,郑州450000 [2]北京中医药大学东方医院,北京100078 [3]天津中医药大学,天津300193 [4]天津中医药大学第一附属医院,天津300381
出 处:《中华中医药杂志》2021年第11期6400-6404,共5页China Journal of Traditional Chinese Medicine and Pharmacy
基 金:国家自然科学基金项目(No.81574018);国家中医药领军人才支持计划(No.国中医药人教发[2018]12号)。
摘 要:目的:观察茸菖胶囊对雌性癫痫模型大鼠动情期雌激素及其受体的影响,探讨茸菖胶囊治疗月经性癫痫的作用机制。方法:选取动情周期规律的大鼠48只,分为正常组、模型组、丙戊酸钠组、拉莫三嗪组、茸菖低剂量组、茸菖高剂量组,每组8只。除正常组外,其余各组大鼠以戊四唑诱导癫痫模型。正常组不作处理;模型组灌服0.9%氯化钠溶液;丙戊酸钠组灌服丙戊酸钠(120mg·kg^(-1)·d^(-1))口服液;拉莫三嗪组灌服拉莫三嗪(12mg·kg^(-1)·d^(-1))药液;茸菖低、高剂量组灌服茸菖胶囊(1.65、3.30g·kg^(-1)·d^(-1))药液;持续灌药28d。后用阴道脱落细胞涂片法选出各组处于动情期大鼠,腹腔注射戊四唑,观察大鼠惊厥行为,酶联免疫吸附测定血清雌二醇(E_(2))、孕酮(P)水平,蛋白免疫印迹法检测海马雌激素受体α(ERα)、雌激素受体β(ERβ)、N-甲基-D-天冬氨酸受体1(NR1)蛋白水平。结果:与正常组比较,模型组血清E;水平及海马ERα、ERβ、NR1蛋白均显著升高(P<0.01);与模型组比较,茸菖高剂量组惊厥潜伏期、强直阵挛潜伏期显著延长(P<0.05),血清E;水平及海马ERα、ERβ、NR1蛋白均显著下降(P<0.05,P<0.01)。结论:茸菖胶囊能够减轻雌性癫痫模型大鼠动情期惊厥发作,其机制可能与抑制血清雌激素水平和下调海马ERα、ERβ、NR1的表达有关。Objective: To observe the effects of Rongchang Capsules on estrogens and its receptors during estrus in female rats with epilepsy, and to explore the mechanism of Rongchang Capsules in treating menstrual epilepsy. Methods: Fortyeight rats with regular menstrual cycle were selected as the research object. There were 8 rats in each group: normal group,model group, sodium valproate group, lamotrigine group, low-dose Rongchang group and high-dose Rongchang group. Except the normal group, a model of epilepsy was made with pentylenetetrazole. The normal group was untreated;the model group was given normal saline;the valproate group was given sodium valproate solution(120 mg·kg^(-1)·d^(-1));the lamotrigine group was given lamotrigine solution(12 mg·kg^(-1)·d^(-1));the low-, high-dose Rongchang groups were given Rongchang Capsules solution(1.65, 3.30 g·kg^(-1)·d^(-1));continuous medication was administered 28 day. After stopping the administration of the drug, the rats in each group were selected by vaginal exfoliation cell smear method. Pentetrazole was injected intraperitoneally to observe the convulsive behavior of the rats. The serum E;and P levels of the rats were measured by enzyme-linked immunosorbent assay. The levels of ERα, ERβ, NR1 protein in rat hippocampus were detected by Western Blot respectively. Results: Compared with the normal group, serum E;levels, hippocampal ERα, ERβ, NR1 protein expression were significantly increased in the model group(P<0.01). Compared with the model group, the convulsion latency and tonic array were significantly shortened in the high-dose Rongchang group(P<0.05), serum E_(2) levels, hippocampal ERα, ERβ, NR1 protein expression were significantly reduced(P<0.05,P<0.01). Conclusion: Rongchang Capsules can alleviate seizures in female rats with epilepsy. The mechanism may be related to the inhibition of serum estrogen levels and the down-regulation of hippocampal ERα, ERβ, NR1 protein expression.
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