蛋白酶体抑制剂MG-132对大鼠失神经肌萎缩的防治作用

Preventive and therapeutic effects of proteasome inhibitor MG-132 on dener-vated muscle atrophy of rats

目的:探讨蛋白酶体抑制剂MG-132对大鼠失神经肌肉萎缩的防治作用.方法:36只SD大鼠随机分为3组,每组12只.A组:50μLMG-132组;B组:100μLMG-132组;C组:对照组.制作成标准的右侧坐骨神经离断,腓肠肌失神经支配模型.分别在A组和B组大鼠失神经腓肠肌局部注射浓度为20μmol/L的蛋白酶体抑制剂MG-13250μL和100μL,1次/d;C组于相同部位注射100μLPBS,1次/d.连续注射1wk后半数处死各组动物,各组剩余动物连续注射4wk后处死,取双侧腓肠肌进行肌肉湿重萎缩率、总蛋白含量、肌细胞直径和横截面积测定,并进行统计学分析.结果:A组和B组肌肉湿重萎缩率、总蛋白含量、肌细胞直径和横截面积注射1wk时分别为(24.5±3.5)%和(18.2±3.3)%,(9.98±0.68)mg/mL和(10.56±0.84)mg/mL,(14.61±1.26)μm和(14.96±1.34)μm,(790.25±12.26)μm2和(800.28±18.98)μm2,与C组相比较差异均具有统计学意义(P<0.05);肌肉湿重萎缩率A组和B组差异具有统计学意义(P<0.05).注射4wk时分别为(60.2±3.7)%和(52.1±4.0)%,(7.04±0.70)mg/mL和(7.96±0.68)mg/mL,(10.63±1.04)μm和(12.16±0.98)μm,(470.48±11.14)μm2和(498.47±10.34)μm2,与C组相比较差别均具有统计学意义(P<0.05).肌肉湿重萎缩率A组和B组差异具有统计学意义(P<0.05).结论:蛋白酶体抑制剂MG-132可以通过抑制肌肉降解的泛素-蛋白酶体途径延缓大鼠失神经肌肉萎缩,并且随时间的延长其作用具有剂量依赖性.

AIM： To investigate the preventive and therapeutic effects of proteasome inhibitor MG-132 on the denervated muscle atrophy of rats. METHODS ： Thirty-six SD were randomly divided into 3 groups, group A： 50 uL MG-132 group; group B： 100 uL MG-132 group; group C： control group, 12 rats in each group. Standard model of denervated gastroenemius muscle was established in right limb of each rat. 50 and 100 uL MG-132 （concentration 20 umol/L）, 100 uL PBS were respectively given by intramuscular injection once muscle of each rat of group A, per day to right gastrocnemius B and C. Six rats of the each group were separately sacrificed after the last injection of the 1st and 4th week, and the gastrocnemius was harvested for measurement of atrophy rate of muscle, total proteins of muscle, diameter and cross section area of myocyte. RESULTS： At the 1 st week postinjectively, atrophy rate of muscle, total proteins of muscle, diameter and cross section area of myocyte in group A and B were （24.5±3.5）% and （18.2±3.3）%, （9.98±0.68） mg/mL and （10. 56 ± 0. 84） mg/mL, （14. 61 ± 1. 26） um and （ 14.96 ± 1.34） um, （790.25 ± 12.26） um^2 and （ 800.28 ± 18.98 ） um^2; there were significant differences from group C （P 〈 0.05）, and also between group A and B in atrophy rate of muscle （ P 〈 0.05 ）. At the 4th week postinjectively, the above indexes were （60.2±3.7）% and（52.1 ±4.0）%, （7.04± 0.70） mg/mL and （ 7.96 ± 0.68 ） mg/mL, （ 10.63 ± 1.04 ） um and （12. 16 ± 0. 98） um, （470.48 ± 11. 14） um^2 and （498.47 ± 10. 34） um^2; there were statistic differences from group C （P〈0.05）, and also between group A and B in the above indexes （ P 〈 0.05 ）. CONCLUSION： Denervated muscle atrophy ean be partly prevented by proteasome inhibitor MG-132 in rats, and the effeets rely on the dose of MG-132 and the injection duration.