阿霉素对大鼠膈肌的毒性损伤作用研究

Protective effect of ligustrazine on rat's diaphragm injured by doxorubicin

目的研究阿霉素对大鼠膈肌的毒性损伤作用,探讨其可能机制。方法Sprague-Dawley大鼠20只,随机分为2组,对照组及阿霉素组各10只。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)、张力-频率曲张(Force-frequency)、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),同时检测膈肌中超氧化物歧化酶(SOD)、丙二醛(MDA)、琥珀酸脱氢酶(SDH)活性,应用电子显微镜观察膈肌组织的超微结构形态变化。结果(1)阿霉素组大鼠膈肌Pt、Po、+dT/dtmax及-dT/dtmax明显低于对照组(P<0.01),(2)予10、20、40、60、100 Hz频率刺激膈肌时,阿霉素组大鼠膈肌张力明显低于对照组(P<0.01)。(3)阿霉素组大鼠膈肌组织的SOD含量明显低于对照组(P<0.01),MDA含量明显高于对照组(P<0.01);阿霉素组大鼠膈肌组织的SDH含量低于对照组(P<0.01)。(6)电子显微镜观察可见阿霉素大鼠膈肌肌纤维断裂、Z线结构模式不清晰、线粒体肿胀变性、部分有空泡变和髓样小体形成。结论阿霉素能使大鼠膈肌产生脂质过氧化,自由基生成增多,SDH活性下降,超微结构受到破坏,损伤膈肌收缩功能。

Objective To study the impairment of doxorubicin on rat＇s diaphragm and the mechanism of impairment. Methods Twenty SD rats were divided into control group （ n = 10 ） and doxorubicin group （ n = 10 ）. Peak twitch tension （ Pt ） , maximum tetanic tension （ Po ） , force-frequency curve, time to peak contraction （ CT ） , half relaxation time （ 1/2RT ） , maximal rates of contraction （ ＋ dT/dtmax ） , maximal rates of relaxation （ -dT/dtmax ） , superoxide dismutase （ SOD ） , malondialdenyde （MDA） and succinate dehydrogenase（ SDH）were measured;and variety of ultrastructures of rates＇ diaphragm were observed. Results （1）Po,Pt, -dT/dtmax and ＋ dT/dtmax in the doxorubicin group were lower than those in the control group（P 〈 0.01） ;（2）Compared with the control group, tetanic force under the stimulus frequency of 10,20,40,60 and 100Hz in the doxorubicin group decreased significantly（ P 〈 0. 01 ）. （ 3 ） SOD in the doxorubicin group was lower than that in the control group（P 〈0. 01）, and MDA in the doxorubicin group increases significantly（P 〈 0. 01）. SDH in the doxorubicin group was lower than that in the control group（P 〈 0. 01）. （6）The ultrastructures under electron microscope indicate that diaphragm fibres in the doxorubicin group fractured, Z lines fluffed, mistochondrions swelled and degenerated. Conclusion Doxorubicin can promote diaphragm to produce more free radicals, reduce SDH, destroy the diaphragmatic ultrastructure and depress contraction function.