兰州大学机构库 >学院待认领
拉莫三嗪对戊四氮慢性致痫大鼠海马细胞凋亡的影响
Alternative TitleEffect of lamotrigine on apoptosis in hippocampus of rats with chronically kindled epilepsy by pentylenetetrazole
雷军
Thesis Advisor王为民
2009-06-26
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword拉莫三嗪 丙戊酸 凋亡 Bcl-2 Bax
Abstract目的:通过观察拉莫三嗪对戊四氮慢性致痫大鼠海马Bcl-2和Bax表达的影响,探讨拉莫三嗪对大鼠海马神经细胞的抗凋亡作用。 方法:选取普通级健康成年雄性Wistar大鼠,按体重随机分为8组,即正常组,模型组,阳性药物对照组(丙戊酸低、中、高剂量组共3组),治疗组(拉莫三嗪低、中、高剂量组共3组),每组10只。模型组,拉莫三嗪治疗组和丙戊酸阳性药物对照组每日给予戊四氮(35mg/ kg• d)腹腔注射达Racine点燃标准,制作慢性癫痫模型。正常组给予同体积的生理盐水腹腔注射。全部点燃后,模型组,拉莫三嗪治疗组和丙戊酸阳性药物对照组,给予戊四氮(35mg/ kg• d)隔日一次腹腔注射维持点燃,而正常组仍给予同体积的生理盐水腹腔注射.在每次腹腔注射戊四氮或者生理盐水后,按Racine标准观察大鼠行为学变化60分钟;同时治疗组和阳性药物对照组给予相应药物剂量灌胃治疗,正常组和模型组给予同体积生理盐水灌胃,共3周。在末次点燃24h内,取各组大鼠进行心脏灌注固定取海马标本,做免疫组化检测海马神经细胞Bcl-2和Bax的表达。 结果:与模型组比较,正常组中Bax、Bcl-2低表达,阳性药物对照各组和治疗各组Bcl-2表达增加而Bax表达下降,差异均有显著统计学意(P<0.001);拉莫三嗪低剂量组与丙戊酸低剂量组比较差异没有统计学意义(BCL-2 P=0.139;Bax P=0.346 P>0.05);拉莫三嗪中剂量组与丙戊酸中剂量组比较差异有统计学意义(Bcl-2 P=0.02 Bax P=0.044 P<0.05);拉莫三嗪高剂量组与丙戊酸高剂量组比较差异有显著统计学意(P<0.01)。 结论:拉莫三嗪和丙戊酸对戊四氮致痫大鼠海马神经细胞均有抑制凋亡的作用,两药在半数致死量的1/30~1/10区间内随剂量增高作用加强。在中高剂量时,拉莫三嗪优于丙戊酸。
Other AbstractObjective:to explore the antiapoptotic effect of lamotrigine on the expression of Bcl-2 and Bax in hippocampus of rats with epilepsy induced chronically by pentylenetetrazole(PTZ). Methods:Eighty healthy adult Wistar rats were randomly divived by weight into eight groups including normal group,model group, lamotrigine treatment groups(lamotrigine low,medium,high dose groups) and valproic acid drug positive groups(valproic acid low ,medium,high dose groups).10 in each group . PTZ(35mg/kg.d)was injected intraperitoneally in the model group and lamotrigine treatment groups and valproic acid drug positive groups every day to Racine kindling criterion (about 2 weeks)to make the chronic epileptic models,and the same volume physiological saline was given to the normal group at the same way.Then the same dose of PTZ(35mg/kg.d)was injected once every other day to maintain kindling meanwhile, the diffenrent-dose valproic acid drug positive groups and lamotrigine treatment groups were gastrically perfused with corresponding dosage of valproic acid and lamotrigine once a day for 3 continuous weeks respectively.And the same volume physiological saline was given to the normal group and model group at the same way .The expression of Bcl-2 and Bax in hippocampal neural cells of all groups were detected by immuno- histochemisty method. Results: Compared with model group , the expression of Bcl-2 and Bax was lower in nomal group;The expression of Bcl-2 was higher ,and that of Bax was lower in diffenrent-dose lamotrigine treatment groups and valproic acid drug positive groups. Compared lamotrigine treatment groups with valproic acid drug positive groups: There were no diffenrences between low-dose groups (BCL-2 P=0.139;Bax P=0.346 P>0.05),There were differences between medium-dose groups(Bcl-2 P=0.02 Bax P=0.044 P<0.05),and there were significant diffenrences between high dose groups(0.001=P<0.01) Conclusion:Both lamotrigine and valproic acid have antiapoptotic effect on hippocampal neural cells of rats with epilepsy induced chronically by PTZ, And higher dose, more effective among 1/30~1/10 median lethal dose.Lamotrigine is better than valproic acid in medium-and high-dose lever.
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/223124
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
雷军. 拉莫三嗪对戊四氮慢性致痫大鼠海马细胞凋亡的影响[D]. 兰州. 兰州大学,2009.
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