不同剂量FTY720对大鼠急性脊髓损伤后Caspase-3表达及细胞凋亡的影响  

Effects of Different Doses of FTY720 on Expression of Caspase-3 and Neural Apoptosis in Rats with Acute Spinal Cord Injury

作　　者：杨梁[1] 吕德成[2] 郑连杰[1] 王朝晖[1] 张伟[3] 李晓天[3] 

机构地区：[1]大连医科大学附属二院骨科,辽宁大连市116027 [2]大连医科大学附属一院骨科,辽宁大连市116011 [3]大连医科大学,辽宁大连市116021

出　　处：《中国康复理论与实践》2012年第6期530-534,共5页Chinese Journal of Rehabilitation Theory and Practice

基　　金：辽宁省教育厅资助课题(编号:L2010105)

摘　　要：目的比较不同剂量FTY720对大鼠急性脊髓损伤后Caspase-3的表达及神经细胞凋亡的影响。方法雌性SD大鼠200只,随机分为5组,每组40只。A组大鼠不打击脊髓,缝合切口后立即以0.3 ml生理盐水灌胃。B、C、D、E组大鼠制作Al-len's T9脊髓损伤模型。B组造模后立即以0.3 ml生理盐水灌胃,C、D、E组分别以FTY720按1 mg/kg、3 mg/kg、5 mg/kg生理盐水稀释至0.3 ml灌胃。分别于术后6 h、12 h、24 h、48 h和72 h取损伤段脊髓超薄切片,行SP免疫组化染色观察Caspase-3表达及TUNEL染色观察细胞凋亡情况,并计算相应时间点免疫组化学染色阳性细胞比值。结果 A组各时间点几乎见不到Caspase-3和细胞凋亡阳性表达。B、C、D、E组均在伤后6 h开始出现凋亡细胞表达,伤后24 h达高峰,伤后48 h开始减弱,伤后72 h进一步减少。伤后各时间点细胞凋亡表达均为B组>C组>D组=E组(P>0.05)>A组(P<0.05)。Caspase-3表达与细胞凋亡同步。相关性检验显示B、C、D组中,FTY720的剂量与Caspase-3表达、细胞凋亡表达呈负相关(P<0.05)。D组和E组中,FTY720剂量与上述指标不相关(P>0.05)。结论 FTY720可以显著减少大鼠急性脊髓损伤后Caspase-3的表达及神经细胞凋亡。FTY720的剂量与其减轻Cas-pase-3表达和细胞凋亡效果之间存在一定量效关系。3 mg/kg是FTY720治疗大鼠急性脊髓损伤的最适剂量。Objective To compare the effects of different doses of FTY720 on inhibiting expression of Caspase-3 and neural apoptosis in rats with acute spinal cord injury（SCI）,and find out the suitable dose.Methods 200 female SD rats were randomly divided into 5 groups with 40 in each group.Group A（laminectomy but not contusion） were administered 0.3 ml normal saline by gavage.SCI model was established by Allen＇s WD method at the T9 level of spinal cord in other groups.Group B were administered 0.3 ml normal saline after modeling.Groups C,D and E were administered 0.3 ml FTY720-saline solution of 1,3 and 5 mg/kg respectively.All the groups were sacrificed at 6 h,12 h,24 h,48 h,72 h（n=8,per each time-point）.Caspase-3 expression was detected with streptavidin-peroxidase immunohistochemistry,and neural apoptosis was detected with the TUNEL method.Results Positive Caspase-3 expression and neural apoptosis were not observed in Group A at 6 h.In Groups B、C、D and E,the number of apoptotic cells increased with increased time of acute SCI,peaked at 24 h after injury,and then gradually reduced.Caspase-3 expression was at equal pace with neural apoptosis.The difference of the number of apoptotic and Caspase-3 expression cells among all groups were significant,with the order Group BGroup CGroup DGroup A（P0.05）.However,there was no significant difference between Group D and Group E（P0.05）.The number of apoptotic and Caspase-3 expression cells negatively correlated with the dose of FTY720 when the dose was less than 3 mg/kg（P0.05）,and there was no relationship when the dose was more than 3 mg/kg（P0.05）.Conclusion FTY720 significantly reduces Caspase-3 expression and neural apoptosis in rats with acute SCI.There is a dose-effect relationship between the dose of FTY720 and the Caspase-3 expression and neural apoptosis.It＇s indicated that 3 mg/ kg is the most appropriate dosage.

关 键 词：FTY720 CASPASE-3 凋亡 脊髓损伤 神经再生 剂量 量效关系 

分 类 号：R651.2[医药卫生—外科学]