摘要
目的探究他克莫司对大鼠脊髓损伤的治疗作用及其对NF-κB/JNK信号通路的调节作用。方法实验大鼠随机分为三组(n=15):假手术组、模型组、他克莫司治疗组;采用Allen’s法建立脊髓损伤动物模型。造模后给予实验大鼠他克莫司(0.3 mg/kg),连续给予21 d。分别在第0、1、7、14、21天进行Basso-Beattie-Bresnahan(BBB)脊髓损伤的行为学评分测试。采用HE染色观察实验大鼠脊髓损伤状态并测定脊髓组织中抗氧化酶活性;采用RT-PCR测定脊髓组织中的IL-4 mRNA和TGF-βmRNA表达量;采用Western blot实验测定脊髓组织中NF-κB/JNK信号通路相关蛋白表达。结果他克莫司能够显著性改善脊髓损伤大鼠的BBB评分(P<0.05),升高SOD、CAT、GPX酶活性并降低MDA含量(P<0.05);并减少脊髓神经元的异常凋亡,降低脊髓组织中IL-4 mRNA、TGF-βmRNA表达和NF-κB p-p65/NF-κB p-p65和p-JNK/JNK蛋白表达量的比值(P<0.05)。结论他克莫司能够显著性改善脊髓损伤,其可能是通过抗氧化、抗炎反应、抗脊髓神经元凋亡,以及抑制NF-κB/JNK信号通路活化而发挥作用的。
Objective To investigate the therapeutic effect of tacrolimus on spinal cord injury rats and its regulation of the NF-κB/JNK pathway.Methods Rats were randomly divided into three groups(n=15):sham group,model group and tacrolimus administration group.The animal model of spinal cord injury was established by Allen’s method.The rats were given tacrolimus(0.3 mg/kg)once a day for 21 days.Basso,Beattie and Bresnahan(BBB)scores were tested on days 0,1,7,14 and 21.Hematoxylin and eosin staining was used to observe the state of spinal cord injury in rats;SOD,CAT,and GPX activity and MDA content in spinal cord tissue were measured by a kit;IL-4 and TGF-beta expression in spinal cord tissue was measured by RT-PCR;NF-κB p-p65,NF-κB p-p65,JNK and p-JNK protein expression was measured in spinal cord tissue by western blots.Results Tacrolimus could significantly improve the BBB score of spinal cord injury rats(P<0.05),increase SOD,CAT,GPX activity,decrease MDA content,reduce abnormal apoptosis of spinal cord neurons,and decrease the expression of IL-4 and TGF-beta and the NF-κB,p-p65 and p-JNK/JNK protein ratios.Conclusions Tacrolimus can significantly improve spinal cord injury,and the mechanism may be related to its anti-oxidative,anti-inflammatory response,and anti-apoptosis activities in spinal cord neurons and inhibition of NF-κB/JNK signaling pathway activation.
作者
张七妹
柴芳
麦宜准
郭仁芬
王光
ZHANG Qimei;CHAI Fang;MAI Yizhun;GUO Renfen;WANG Guang(Sanya People’s Hospital,Sanya 572000,China;Hainan Medical University,Haikou 570102)
出处
《中国比较医学杂志》
CAS
北大核心
2020年第4期27-32,共6页
Chinese Journal of Comparative Medicine
基金
海南省卫生计生行业科研项目(1601320675A2003)。
