吡咯烷二硫代氨基甲酸酯延缓失神经肌萎缩的实验研究  

EFFECT OF PYRROLIDINE DITHIOCARBAMATE ON RETARDING DENERVATED SKELETAL MUSCULAR ATROPHY

作　　者：何祥乐[1] 梁炳生[1] 

机构地区：[1]山西医科大学第二医院骨科太原,030001

出　　处：《中国修复重建外科杂志》2011年第2期239-242,共4页Chinese Journal of Reparative and Reconstructive Surgery

摘　　要：目的研究NF-κB抑制剂吡咯烷二硫代氨基甲酸酯(pyrrolidine dithiocarbamate,PDTC)延缓失神经肌萎缩的效果及其机制。方法健康成年Wistar大鼠30只,雌雄不限,体重(200±10)g。实验动物随机分为3组,即正常对照组(A组,n=6)、失神经对照组(B组,n=12)和PDTC治疗组(C组,n=12)。A组仅暴露右侧坐骨神经并不切断;B、C组切断右侧坐骨神经0.7～1.0 cm,建立右下肢腓肠肌失神经支配模型后,C组采用PDTC 100 mg/(kg?d)腹腔注射,B组以等量生理盐水腹腔注射。A组术后当天和B、C组术后14、28 d,完整分离双侧腓肠肌检测肌肉湿重维持率,采用Western blot检测腓肠肌NF-κB p65表达水平,激光共聚焦扫描显微镜观察线粒体通透性转换孔(mitochondrial permeability transition pore,MPTP)开放情况,TUNEL法检测细胞凋亡情况。结果 A组腓肠肌湿重维持率为1.039±0.115;与A组比较,B、C组各时间点腓肠肌湿重维持率均明显下降,且C组腓肠肌湿重维持率明显高于同期B组,差异均有统计学意义(P<0.05)。A组NF-κB p65表达为0.224±0.041;与A组比较,B、C组各时间点NF-κB p65表达明显升高,且C组NF-κB p65表达明显低于同期B组,差异均有统计学意义(P<0.05)。A组MPTP荧光强度为31.582±1.754;与A组比较,B、C组各时间点MPTP荧光强度均降低,且C组MPTP荧光强度明显高于同期B组,差异均有统计学意义(P<0.05)。A组有少量细胞凋亡,细胞凋亡率为4.542%±0.722%;与A组比较,B、C组各时间点细胞凋亡率均明显增加,且C组细胞凋亡率明显低于同期B组,差异均有统计学意义(P<0.05)。结论 PDTC可有效延缓失神经肌萎缩,其作用机制与抑制NF-κB表达、降低骨骼肌细胞MPTP开放及抑制骨骼肌细胞凋亡有关。Objective To investigate the preventive and therapeutic effects and the mechanisms of pyrrolidine dithiocarbamate（PDTC） on the atrophy of denervated skeletal muscle.Methods Thirty adult Wistar rats of either gender,weighing（200 ± 10） g were randomly divided into 3 groups： group A（n=6,control group）,group B（n=12,denervation group）,and group C（n=12,PDTC treatment group）.The sciatic nerves of the rats were only exposed without cutting off in group A,and the rats were made denervated gastrocnemius models in groups B and C.PDTC of 100 mg/（kgod） was injected peritoneally in group C and an intraperitoneal injection of the same amount normal saline was given in group B.After 14 and 28 days,the gastrocnemius was harvested to measure the ratio of muscle wet weight;the levels of nuclear factor of κB（NF-κB） p65 protein and the opening of the mitochondrial permeability transition pore（MPTP） in the gastrocnemius were detected respectively by Western blot and laser confocal scanning microscope;and the apoptotic cells in atrophic muscle were measured with TUNEL.Results The ratio of muscle wet weight in group A was 1.039 ± 0.115,and it significantly decreased in groups B and C（P 〈 0.05）;after 14 and 28 days of operation,the ratio of muscle wet weight in group C significantly increased when compared with those in group B（P 〈 0.05）.The expression of NF-κB p65 protein in group A was 0.224 ± 0.041;the expressions of NF-κB p65 in groups B and C significantly increased when compared with that in group A（P 〈 0.05）;however,the expression of NF-κB p65 in group C was significantly lower than that in group B（P 〈 0.05）.The MPTP fluorescence intensity in group A was 31.582 ± 1.754;the MPTP fluorescence intensity was significantly lower in groups B and C than in group A（P 〈 0.05）,and the MPTP fluorescence intensity in group C was significantly higher than that in group B（P 〈 0.05）.The rate of apoptosis in group A was 4.542% ± 0.722%;after 14 and 28 days of operatio

关 键 词：吡咯烷二硫代氨基甲酸酯 NF-KB 失神经肌萎缩 线粒体通透性转换孔 细胞凋亡 大鼠 

分 类 号：R965[医药卫生—药理学]