基质金属蛋白酶9的表达在慢性酒精中毒性肌损伤中的作用  

Effects of the expression of matrix metalloproteinase 9 on chronic alcoholic muscle injury

作　　者：王剑锋[1] 刘艳丽[1] 王永平[2] 初海鹰[3] 张利[1] 程学英[1] 赵华[1] 金伟[3] 

机构地区：[1]大连市中心医院神经内二科,116033 [2]中国医科大学临床医学系94期9班 [3]大连医科大学组胚研究室

出　　处：《中华神经科杂志》2010年第3期211-215,共5页Chinese Journal of Neurology

摘　　要：目的探讨基质金属蛋白酶9（MMP-9）在慢性酒精中毒性肌损伤（chronic alcoholic muscle injury, CAMI）发病过程中的作用。方法60只雄性sD大鼠随机分为对照组（A组，15只，生理盐水灌胃）和实验组（B组，45只，灌酒），建立CAMI模型。将A组再随机分为A1～3组（分别于生理盐水灌胃第2周、第6周和第12周末处死，每组5只）；B组再随机分为Bl～3组（分别于灌酒第2周、第6周和第12周末处死，每组15只）。光镜下观察大鼠骨骼肌病理学改变；逆转录-聚合酶链反应检测大鼠骨骼肌MMP-9的mRNA表达的动态改变；Western blot检测大鼠骨骼肌MMP-9蛋白的表达变化；明胶酶谱法检测大鼠骨骼肌MMP-9的酶活性变化。结果组织化学结果显示，B组大鼠跖肌Ⅱ型肌纤维萎缩，间质炎性细胞浸润和纤维增生，其中I型胶原增生明显。Al组与B1组大鼠骨骼肌MMP-9mRNA的表达甚少，Western blot和酶谱法检测仅显示MMP-9前体型。B2组大鼠跖肌MMP-9mRNA表达（0．0579±0．0046）较A2组（0．0198±0．0023）增高（t=-9．151，P〈0．01），B3组大鼠跖肌和腓肠肌MMP-9mRNA的表达（0．1417±0．0116、0．0599±0．0057）均较A3组（0．0249±0．0049、0．0237±0．0021）增高（t=-18．095，P〈0．01；t=一5．933，P〈0．05）。同时，Western blot和酶谱法也检测出B3组大鼠腓肠肌和跖肌活性型MMP-9的表达量及酶活性进一步增强，与B2组相比差异有统计学意义。结论MMP-9的表达和活性增高可能参与了骨骼肌间质纤维增生，促进了CAMI。Objective To investigate the effects of matrix metalloproteinase 9 （MMP-9） on chronic alcohol muscle injury （CAMI）. Methods Sixty male Sprague-Dawley （SD） rats were randomly divided into control group （A group, 15 rats ） and experimental group （B group, 45 rats）. All rats were administered intragastrically by gavage. Group A was treated with physiological saline. Group B was treated with alcohol. Initial dose was 4 g · kg- 1 ·d-1. Then dose was increased by 2 g · kg-1 · d-1 weekly until 10 g·kg-1 ·d-1. Group A were randomly divided into 3 subset groups （A1-3）, which would be sacrificed at 2, 6 and 12 weeks after feeding physiological saline. Each group had 5 rats. Group B were randomly divided into 3 subset groups （ B1-3 ）, which would be sacrificed at 2, 6 and 12 weeks after feeding alcohol. Each group had 15 rats. Then the histopathological changes in rat skeletal muscles were observed by HE and NADH-TR staining. The expression of MMP-9 mRNA was detected by RT-PCR. MMP- 9 protein was detected by Western blot. The enzymatic activity of MMP-9 weas detected by gelatin zymography. Results The observation of histocbemistry showed that there were obviously atrophic type-Ⅱ muscle fibers of plantaris in the B group rats, infiltration of inflammatory cells and accrementition of connective tissue between muscles, in which type- I collagen was obviously proliferative. The expression of MMP-9 mRNA in group A1 and group B1 was much lower. The precursor of MMP-9 in group A1 and group B1 was detected by Western blot and gelatin zymography. The mRNA expression of MMP-9 of plantaris in the group B2（0. 0579 ±0. 0046） was sigmificantlv elevated than that in the grouo A2（0. 0198 ±0. 0023. t =-9. 151 ,P 〈0. 01 ）. The mRNA expression of MMP-9 of plantaris and gastrocnemius in the group B3（0. 1417 ± 0. 0116, 0. 0599 ± 0. 0057 ） was significantly higher than that in the group A3 （0. 0249 ＋ 0. 0049, t = - 18. 095, P 〈 0. 01 ;0. 0237 ± 0. 0021, t = - 5.933, P 〈 0. 05 ）. Me

关 键 词：酒精中毒 肌疾病 基质金属蛋白酶9 

分 类 号：R595.6[医药卫生—内科学]