摘要目的 动态观察低硒对大鼠在体心功能及线粒体超微结构的影响,探讨低硒致心肌损伤的机制.方法 断乳2周清洁级SD大鼠48只,按体质量随机分为低硒(LS)组和对照(NC)组,每组24只,雌雄各半.对照组给予常规饲料(硒含量0.10～ 0.30 mg/kg)喂养,低硒组给予人工合成低硒饲料(硒含量0.01 mg/kg)喂养.两组大鼠分别在喂养10、20、30、40周后,各选取6只,雌雄各半,2,3-二氨基奈荧光法检测血硒水平；颈动脉插管检测大鼠在体心功能；电子天平称心脏重量；透射电镜下观察心肌线粒体的超微结构并用体视学方法对线粒体结构的变化情况进行定量分析.结果 与NC组比较[(0.421±0.076)、(0.409±0.057)、(0.416±0.033)、(0.386±0.050)mg/L],LS组大鼠喂养10、20、30、40周后血硒降低[(0.102±0.018)、(0.053±0.012)、(0.045±0.014)、(0.027±0.008) mg/L,P均＜0.05].大鼠喂养到20、30、40周时,LS组左心室峰值收缩压(LVSP)[(113.30±2.21)、(103.82±5.24)、(97.74±2.87)mm Hg,1 mm Hg=0.133 kPa]和左心室内压最大上升速率(+dp/dtmax)[(7366.10±455.61)、(6160.68±402.17)、(5381.21±646.72)mm Hg· s-1]均明显低于相应NC组[(130.30±3.72)、(118.97±5.31)、(120.08±3.29)mm Hg,(10 430.00±808.56)、(8582.62±621.14)、(8295.88±1318.29)mm Hg·s-1,P均＜0.05],且LVSP和+dp/dtmax均随低硒喂养时间延长而逐渐减低(P均＜ 0.05).大鼠喂养到20、30、40周时,LS组心脏与体质量之比(HW/BW×100,0.2859±0.0081、0.2948±0.0171、0.2949±0.0056)、左心室与体质量之比(LVW/BW×100,0.2302±0.0041、0.2387±0.0131、0.2386±0.0024)、左心室与心脏重量之比(LVW/HW,0.8063±0.0122、0.8104±0.0031、0.8098±0.0109)均高于NC组(0.2798±0.0103、0.2761±0.0128、0.2718±0.0051,0.2185±0.0094、0.2145±0.0131、0.2123±0.0027,0.7813±0.0210、0.7751±0.0165、0.7815±0.0100,P均＜0.05).电镜观察可见LS组大鼠心肌线粒体嵴膜减少,线粒体明显肿胀；体视学检测大鼠在喂养到10、20、30、40周时,LS组体密度(Vv)[(0.3108±0.0053)％、(0.3286±0.0036)％、(0.3877±0.0211)％、(0.3990±0.0115)％]和面密度(Sv)[(0.0284±0.0002)、(0.0295±0.0007)、(0.0338±0.0026)、(0.0332±0.0004) μm-1]高于NC组[(0.2402±0.0143)％、(0.2375±0.0241)％、(0.2657±0.0239)％、(0.2892±0.0302)％,(0.0231±0.0015)、(0.0221±0.0019)、(0.0241±0.0014)、(0.0273±0.0028)μm-1,P均＜ 0.05]；在20、30、40周时,LS组比表面积(Rsv)[(0.0899±0.0015)、(0.0868±0.0031)、(0.0835±0.0013)μm-1]低于NC组[(0.0939±0.0020)、(0.0915±0.0023)、(0.0946±0.0021)μm-1,P均＜0.05].相关性分析显示,Rsv分别与LVSP和+dp/dtmax相关(r值分别为0.508、0.502,P均＜0.01).结论 低硒可导致大鼠心肌线粒体超微结构异常,并导致心脏功能发生变化,以收缩功能损伤更为明显；线粒体的损伤与心功能减退具有相关性；线粒体在低硒致心功能受损过程中发挥重要作用.

abstractsObjective To dynamically observe the cardiac function in vivo and ultrastructure of myocardial mitochondria in selenium deficiency rats so as to provide a theoretical basis for revealing the mechanism of myocardial injury induced by selenium deficiency.Methods Forty eight of two-week old SD rats were randomly divided into low-selenium(LS) group and normal control(NC) group,24 rats in each group(female 12,male 12).Normal group was fed with Se-normal food (selenium content 0.10-0.30 mg/kg),low-selenium group was fed with Se-deficient food(selenium content 0.01 mg/kg).At four time points(10 w,20 w,30 w and 40 w) the following were done:fluorometric determination of whole blood Se levels with 2,3-diaminonaphthalene;measuring hemodynamics in vivo and cardiac weight; transmission electron microscope(TEM) observation of mitochondrial ultrastructure and quantitative analysis of mitochondrial structure changes using stereological methods.Results After feeding for 10,20,30 and 40 weeks,the blood selenium level of LS group[(0.102 ± 0.018),(0.053 ± 0.012),(0.045 ± 0.014),(0.027 ± 0.008)mg/L] decreased significantly compared with NC group[(0.421 ± 0.076),(0.409 ± 0.057),(0.416 ± 0.033),(0.386 ± 0.050)mg/L,all P ＜ 0.05].When the rats were fed for 20,30 and 40 weeks,the left ventricular systolic pressure (LVSP) [(113.30 ± 2.21),(103.82 ± 5.24),(97.74 ± 2.87) mm Hg,1 mm Hg =0.133 kPa]and maximum rate of rise of left ventricular pressure (+dp/dtmax) [(7366.10 ± 455.61),(6160.68 ± 402.17),(5381.21 ± 646.72)mm Hg·s-1] of LS group decreased significantly compared with NC group[(130.30± 3.72)mm Hg,(118.97 ± 5.31)mm Hg,(120.08 ± 3.29)mm Hg,(10 430.00 ± 808.56)mm Hg·s-1,(8582.62 ± 621.14) mm Hg·s-1,(8295.88± 1318.29)mm Hg·s-1,all P＜ 0.05],and the reduction gradually reduced with prolonged feeding with low selenium(all P ＜ 0.05).The heart weight(HW)/body weight(BW) ratio × 100(0.2859 ± 0.0081,0.2948 ± 0.0171,0.2949 ± 0.0056),left ventricular weight(LVW)/BW ratio × 100(0.2302 ± 0.0041,0.2387 ± 0.0131,0.2386 ± 0.0024) and LVW/HW ratio(0.8063 ± 0.0122,0.8104 ± 0.0031,0.8098 ± 0.0109) of LS group were significantly higher than those in NC group(0.2798 ± 0.0103,0.2761 ± 0.0128,0.2718 ± 0.0051,0.2185 ± 0.0094,0.2145 ± 0.0131,0.2123 ± 0.0027,0.7813 ± 0.0210,0.7751 ± 0.0165,0.7815 ± 0.0100,all P ＜ 0.05).Observed by TEM,the cristae membrane of mitochondria reduced,and mitochondria swelled significantly.When the rats were fed for 20,30 and 40 weeks,volume density(Vv)[(0.3108 ± 0.0053)％,(0.3286 ± 0.0036)％,(0.3877 ± 0.0211)％,(0.3990 ± 0.0115)％] and surface density(Sv) [0.0284 ± 0.0002),(0.0295 ± 0.0007),(0.0338 ± 0.0026),(0.0332 ± 0.0004)μm-1] of mitochondria in LS group increased significantly,compared with those of NC group[(0.2402 ± 0.0143)％,(0.2375 ± 0.0241)％,(0.2657 ± 0.0239)％,(0.2892 ± 0.0302)％,(0.0231 ± 0.0015)μm-1,(0.0221 ± 0.0019)μm-1,(0.0241 ± 0.0014)μm-1,(0.0273 ± 0.0028)μm-1,all P＜ 0.05],and specific surface(Rsv) of LS group[(0.0899 ± 0.0015),(0.0868 ± 0.0031),(0.0835 ± 0.0013)μm-1] reduced,compared with those of NC group[(0.0939 ± 0.0020),(0.0915 ± 0.0023),(0.0946 ± 0.0021)μm-1,all P ＜ 0.05].The correlation analysis indicated that Rsv was positively correlated with LVSP and +dp/dtmax,and the correlation coefficients were 0.508 and 0.502,respectively (all P ＜ 0.01).Conclusions Selenium deficiency can lead to abnormalities of mitochondrial ultrastructure and changes in cardiac function,and among the changes of cardiac function,systolic dysfunction is more apparent.Mitochondria damage and cardiac dysfunction is correlated.Mitochondria plays an important role in cardiac dysfunction caused by selenium deficiency.