绞股蓝总皂甙对阿霉素致大鼠膈肌收缩功能及线粒体超微结构损伤的影响

The effect of gypenosides on adriamycin-induced diaphragmatic contractile function and mitochondrial ultrastructure

目的:探讨绞股蓝总皂甙(gypenosides,GP)对阿霉素(adriamycin,ADM)致大鼠膈肌收缩功能和线粒体超微结构损伤的影响。方法:将24只成年雄性SD大鼠随机分成对照(CON)组、ADM组和ADM+绞股蓝总皂甙(ADM+GP)组,每组8只。除CON组外,其余各组给予ADM2.0mg/kg腹腔注射,隔日1次,共6次,复制ADM毒性的动物模型。CON组大鼠腹腔注射等量的生理盐水,给予GP250mg·kg-1·d-1灌胃,给药容量为10ml/kg,连续4周;CON组和ADM组给予等量的纯净水。应用体外灌流大鼠膈肌条的方法,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)和张力-频率关系的变化;测定膈肌组织超氧化物歧化酶(SOD)、琥珀酸脱氢酶(SDH)的活性和丙二醛(MDA)的含量;电镜观察膈肌组织超微结构的变化。结果:ADM组Pt、Po值均明显低于CON组(P<0.01),ADM+GP组均高于ADM组(P<0.05～P<0.01);ADM组CT和1/2RT与CON组相比明显延长(P<0.01),ADM+GP组明显改善(P<0.01)。给予10、20、40、60、80、100Hz频率的方波电压刺激膈肌条,ADM组、ADM+GP组的张力明显低于CON组,80、100Hz频率下ADM+GP组较ADM组增大(P<0.05～P<0.01)。SOD、SDH活性ADM组明显低于CON组(P<0.01),ADM+GP组高于ADM组(P<0.05～P<0.01);MDA含量ADM组明显高于CON组(P<0.01),ADM+GP组低于ADM组(P<0.01)。电镜显示绞股蓝总皂甙可减轻ADM导致的膈肌组织线粒体超微结构的损伤。结论:绞股蓝总皂甙可减轻ADM致大鼠膈肌收缩功能和超微结构损伤作用。

Objective：To study the influence of gypenosides （GP） on the diaphragmatic contractile function and mitochondrial ultrastructure induced by adriamycin （ADM） in rats. Methods：Twenty-four adult male Sprague-Dawley rats were randomly divided into control（ CON）group,adriamycin diaphragm toxicity（ADM） group and adriamycin plus gypenosides（ ADM ＋ GP） group. Each group consisted of 8 rats. ADM group and ADM ＋ GP group were injected 2.0 mg/kg ADM intraperitoneally for 6 times every other day, and CON group were injected saline of the same volume and received 250 mg/kg gypenosides per day orally in a dose of 10 ml/kg for four weeks. Meanwhile, pure water was given to ADM group and CON group. The diaphragm contractility was assessed by peak twitch tension （Pt）, maximum tetanic tension（ Po）, time to peak contraction（ CT）, half relaxation time （1/2RT）, and force-frequency curve by in vitro perfusion of diaphragm strips. The activity of SOD, SDH and the content of MDA were determined. The microchondrial uhrastructures of diaphragm were examined by electron microscope. Results ： Compared with CON group, Pt and Po of ADM group were lower（ P 〈 0.05 to P〈0.01） ,but Pt and Po of ADM ＋ GP group were significantly higher than those of ADM group（P 〈0.05 to P 〈0.01 ） ; CT and 1/2RT were significant different between ADM ＋ GP group and CON group. Compared with CON group, the tetanic force under the stimulus frequency of 10,20,40,60,80,100 Hz in ADM group and ADM ＋ GP group decreased significantly. Under the stimulus frequency of 80 and 100 Hz,the tetanic force in ADM ＋ GP group was higher than that in ADM group（P 〈 0.05 to P 〈 0.01 ）. The activities of SOD and SDH in ADM group were lower than those in CON group and ADM ＋ GP group（ P 〈 0.05 to P 〈 0.01 ）, while the content of MDA in ADM group was remarkably higher （ P 〈 0.01 ）. Transmission electron microscopic morphometry showed that gypenosides could ease the diaphragm microchondrial ultrastructural patho-aheration induced by ADM. Conclusions：Gypenosides may lessen the injury of the diaphragmatic contractile function and mitochondrial uhrastructure induced by ADM.