阿霉素中毒大鼠膈肌骨架蛋白和肌浆网钙泵的表达变化及意义  

The changes and significance in mRNA expressions of diaphragmatic cytoskeletal proteins and sarcoplasmic reticulum Ca^(2+)-ATPase in adriamycin-induced cytotoxicity in rats

作　　者：胡杰[1] 于影[1] 高琴[1] 关宿东[1] 

机构地区：[1]蚌埠医学院生理学教研室,安徽蚌埠233003

出　　处：《中国药理学通报》2010年第2期244-247,共4页Chinese Pharmacological Bulletin

基　　金：安徽省教育厅自然科学基金资助项目(NoKJ2007B018)

摘　　要：目的观察不同剂量阿霉素诱导大鼠膈肌急性损伤时膈肌收缩特性的变化与大鼠膈肌细胞骨架蛋白和肌浆网钙泵表达变化的关系。方法一次性腹腔注射阿霉素制备急性膈肌损伤动物模型,♂SD大鼠随机分成:阿霉素低剂量组(10mg·kg-1)、中剂量组(20mg·kg-1)和高剂量组(40mg·kg-1)及对照组,每组10只。对照组用生理盐水腹腔注射。3d后剖胸取膈肌,应用体外灌流大鼠膈肌肌条方法,分别测量其单收缩张力(Pt)、最大强直张力(Po)、峰值收缩时间(CT)、半舒张时间(1/2RT),张力最大上升速度(+dt/dtmax)及张力最大下降速度(-dt/dtmax)。应用逆转录聚合酶链反应(RT-PCR)测定膈肌骨架蛋白肌联蛋白(titin)、伴肌动蛋白(nebulin)和肌浆网钙泵(sarcoplasmic reticulum Ca2+-ATPase,SERCA)mRNA的表达。结果与对照组相比,阿霉素中、高剂量模型组大鼠膈肌Pt,Po,±dt/dtmax下降(P<0.01),CT、1/2RT延长(P<0.01)。阿霉素中毒大鼠膈肌各基因表达较对照组相比分别降低(P<0.01)。结论阿霉素中毒大鼠膈肌细胞膈肌骨架蛋白titin、nebulin和SERCA mRNA表达下调,并可能与膈肌张力改变有关。Aim To observe the changes of diaphragm contractility and cytoskeletal proteins titin, nebulin and sarcoplasmic rcticulum Ca^2＋ -ATPase gene expressions in adriamycin-induced cytotoxicity in rats. Methods The animal models of diaphragm damage were duplicated by injecting adriamycin into abdominal cavity one time. Forty male sprague-dawley rats were randomly divided into four groups（ n = 10 ） ：Three groups received adriamycin in low,middle and high dosage（ 10,20 and 40 mg· kg^-1）respectively. Meanwhile, the normal saline was given to rats in control groups. Three days later, these rats were killed, and the diaphragm was removed by thoracotomy. The diaphragm contractility was assessed in isolated diaphragm strips perfusion by these paramemters including peak twitch tension （ Pt）, maximum tetanic tension （Po）, time to peak contraction （ CT）, half relaxaion time （ 1/2RT）, maximal rates ofcontraction （ ＋ dt/dtmax ） and maximal rates of relaxation （ - dt/dtmax）. The expressions of titin,nebulin and sarcoplasmic reticulum Ca^2＋ -ATPase （SERCA）at mRNA level were detected by RT-PCR analysis. Results In contrast to those in control group, Po, Pt, ＋ dt/dtmax in the adriamycin group were lower （ P 〈 0. 01 ） ; CT, 1/ 2RT in the adriamycin group increased significantly（ P 〈0. 01 ）. The levels of titin, nebulin and SERCA gene expressions in middle-dose group were lower than those in control group （P 〈 0.01 ）. Conclusions The mRNA levels of titin, nebulin and SERCA of diaphragm are down-regulated in adriamycin-induced cytotoxicity in rats. It may be associated with the decline of diaphragm contractility.

关 键 词：阿霉素 膈肌 肌联蛋白 伴肌动蛋白 肌浆网钙泵 基因表达 

分 类 号：R979.11[医药卫生—药品] R730.53[医药卫生—药学]