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目的探讨环孢素对未成熟脑惊厥性脑损伤大鼠多药耐药基因表达的抑制作用及其剂量依赖性和不良反应。方法 21日龄雄性SD大鼠67只分为5组:假手术组(A组)、模型对照组(B组)、环孢素10mg.kg-1干预组(C组)、环孢素5mg.kg-1干预组(D组)、环孢素25mg.kg-1干预组(E组),22日龄时制作氯化锂-匹鲁卡品癫模型(A组除外),采用环孢素每次10mg.kg-1、5mg.kg-1、25mg.kg-1分别在造模后6h、30h、54h腹腔注射干预,观察大鼠造模72h病死率、行为变化、体质量变化、脑海马CA1区电镜神经元形态变化及多药耐药基因产物P-糖蛋白(P-gp)表达水平。结果 1.总体病死率为26.9%,B组病死率为16.7%,采用环孢素干预,最小剂量5mg.kg-1.次-1干预可显著降低病死率,达到A组水平,而中间剂量10mg.kg-1.次-1干预也可显著降低病死率至9.1%,但25mg.kg-1.次-1干预可提高病死率至38.5%。2.B组行为能力差,E组行为能力最差,而D组行为能力与A组接近。3.各组间体质量变化无明显差异。4.环孢素干预可以减轻惊厥幼鼠脑海马CA1区神经细胞水肿程度,减轻凋亡核固缩程度,减轻线粒体水肿,保护细胞间连接,但C、D、E组间差别不明显。5.B组脑海马CA1区多药耐药基因表达产物P-gp的灰度值及阳性细胞数分别为110.44±16.70及(1444.44±271.85)mm-2,环孢素干预可以使其表达显著降低,D组与C组效果比较差异无统计学意义,E组也有降低作用,虽有统计学意义,但不及C、D组作用明显。结论环孢素可以通过降低惊厥幼年雄性SD大鼠脑P-gp表达水平对未成熟的惊厥性脑损伤后多药耐药基因表达进行抑制,环孢素中小剂量应用效果明显,5mg.kg-1.次-1连用3次效果最佳,且不良反应不明显。
Objective To investigate the inhibitory effect of cyclosporine on the expression of multidrug resistance gene in immature cerebral ecnotic injury rats and its dose-dependent and adverse reactions. Methods Sixty-seven male SD rats, 21 days old, were divided into 5 groups: sham operation group (A), model control group (B), cyclosporine 10 mg.kg-1 intervention group (C) (group D), cyclosporine 25mg.kg-1 intervention group (group E), and the model of lithium-pilocarpine epilepsy was made on the 22nd day (except group A) Sparine 10mg.kg-1, 5mg.kg-1 and 25mg.kg-1 were injected intraperitoneally at 6h, 30h and 54h after modeling to observe the mortality, behavior change and weight change , The morphological changes of neurons in CA1 area of hippocampus and the expression of P-glycoprotein (P-gp). Results 1. The overall mortality was 26.9%, and the mortality in group B was 16.7%. With cyclosporine intervention, the minimum dose of 5mg.kg-1. The intervention of sub-1 significantly reduced the mortality and reached the level of group A, while the median dose 10mg.kg-1. The second intervention can also significantly reduce the mortality rate to 9.1%, but 25mg.kg-1. Sub-1 intervention can increase the mortality rate to 38.5%. Group B had poor behavioral abilities, Group E had the worst behavioral abilities, and Group D had similar abilities to Group A. No significant difference in body weight between groups. Cyclosporine intervention can reduce neuronal edema in hippocampal CA1 area, attenuate the degree of nuclear pyknosis, reduce mitochondrial edema and protect cell junctions in young rats with convulsion, but there is no significant difference between C, D and E groups. The gray value and the number of positive cells of P-gp in hippocampal CA1 region of group B were 110.44 ± 16.70 and (1444.44 ± 271.85) mm-2, respectively. Cyclosporine intervention could make the expression of P-gp significantly Reduced, the difference between group D and group C was not statistically significant, group E also had a reduction effect, though statistically significant, but not as obvious as group C and group D. Conclusion Cyclosporine can inhibit the expression of multidrug resistance gene after immature seizure in traumatic brain injury by decreasing the expression of P-gp in young male SD rats. 1 times -1 for 3 times the best, and adverse reactions is not obvious.