胰岛素干预对糖尿病大鼠左室心肌细胞收缩舒张功能的影响

Effect of insulin treatment on systolic and diastolic function of left ventricular cardiomyocytes in diabetic rats

目的 探讨小剂量胰岛素干预下糖尿病大鼠左室心肌细胞收缩舒张功能、细胞超微结构和整体心脏功能变化.方法 将25只大鼠随机分为糖尿病组（DM组,9只）、胰岛素干预组（INS组,9只）和对照组（CN组,7只）,DM组和INS组腹腔注射链脲佐菌素建立糖尿病大鼠模型.成模后INS组每天给予皮下注射胰岛素.应用超声心动图、可视化动缘探测系统和透射电镜在干预8周时观测3组大鼠左室整体结构功能和心肌细胞收缩舒张功能的改变以及超微结构的变化.结果 超声心动图示,DM组较CN组左室舒张末内径（LVEDD）与收缩末内径（LVESD）增大,收缩期室间隔厚度（IVSs）、左室后壁厚度（LVPWs）及左室射血分数（LVEF）减低（P均＜0.05）;INS组较DM组LVESD减小,LVEF增加（P均＜0.05）.单心肌细胞功能测定结果示,DM组较CN组左室心肌细胞长度缩短,收缩幅值（PS％）与最大缩短、复长速率（±dL/dt）减低,收缩达峰时程（TPS）及舒张90％时程（TR90）延长（P均＜0.05）;INS组较DM组心肌细胞长度、PS％、＋dL/dt、-dL/dt、TPS及TR90均有所改善（P均＜0.05）.透射电镜示,DM组心肌细胞肌丝断裂溶解,线粒体聚集肿胀,胶原纤维、糖原颗粒沉积,而INS组心肌超微结构异常较DM组减轻.结论 小剂量胰岛素可改善糖尿病所致心肌结构和功能的异常,有效延缓糖尿病心肌病变的演进,具有明显的心肌保护作用.

Objective To explore the effect of insulin treatment at low doses on systolic and diastolic function of left ventricular cardiomyocytes,myocardial ultrastructure and the whole cardiac function in diabetes rats.Methods Twenty-five rats were randomly divided into three groups：diabetes mellitus（DM） group（n =9）,insulin treatment（INS） group（n =9） and control（CN） group（n =7）.The rats in INS group were hypodermically injected with insulin since the DM models were established through intraperitoneal injection of streptozotocin.Echocardiography,video-based edge-detector system and transmission electron microscope were performed respectively at the point of week 8 to observe the changes of myocardial ultrastructure,systolic and diastolic function of cardiomyocytes as well as changes of whole cardiac structure and function in left ventricle（LV）.Results Echocardiography suggested that in contrast to CN group,DM group showed larger LV end-systolic diameter （LVESD）and end-diastolic diameters （LVEDD） [LVEDD：（6.00 ± 0.54）mm vs （4.89 ± 0.29）mm; LVESD：（3.90 ± 0.53）mm vs （2.39 ± 0.41） mm,respectively],thinner systolic interventricular septum（IVSs） [（2.11 ± 0.24）mm vs （3.04 ± 0.31）mm] and LV posterior wall（LVPWs） [（2.16 ± 0.20） mm vs （2.94 ± 0.28） mm],and decreased LV ejection fraction （LVEF）[（63.5 ± 8.4）％ vs （82.3 ± 6.1）％]（all P ＜0.05）.INS group indicated smaller LVESD[（3.21 ± 0.44）mm vs （3.90± 0.53）mm] and increased LVEF[（71.5 ± 8.5）％ vs （63.5 ± 8.4）％] compared to DM group（all P ＜0.05）.Furthermore,single cardiomyocyte function assessments demonstrated that cell length [（113.88 ± 13.05）μm vs （128.72 ± 11.62）μm] shortened,peak shortening value（PS％） [（6.61 ± 1.45） ％ vs （8.65 ± 1.29）％] and maximal velocity of shortening and relengthening （± dL/dt） [＋ dL/dt：（235.35 ± 81.76）μm/s vs （413.33 ± 71.33）μm/s;-dL/dt（-195.60 ± 72.81）μm/s vs （-316.53 ± 56.11）μm/s] reduced,and time to peak shortening （TPS） [（177.11 ± 30.36） ms vs （119.34 ± 25.27） ms] together with time from peak to 90％ relaxation（TR90）[（186.98 ± 39.17）ms vs （136.89 ± 35.61）ms] prolonged in the DM group compared with CN group （all P ＜0.05）.While INS group ameliorated abnormalities of cell length [（119.86± 12.61） μm vs （113.88 ± 13.05）μm],PS％ [（7.26 ± 1.34）％ vs （6.61 ± 1.45）％],＋ dL/dt [（294.25±68.11）μm/s vs （235.35 ± 81.76）μm/s],dL/dt[（240.34± 71.31）μm/s vs （-195.60± 72.81）μm/s],TPS[（160.10 ± 28.19）ms vs （177.11 ± 30.36）ms] and TR90 [（168.26 ± 38.05）ms vs （186.98 ± 39.17）ms] compared with DM group （all P ＜0.05）.Moreover,transmission electron microscope indicated that DM group showed fractured and dissolved myofilament,swollen and aggregated mitochondria and deposited collagen fibers and glycogen granules.But myocardial ultrastructure abnormalities in INS group were ameliorated compared with DM group.Conclusions Low doses insulin treatment could ameliorate the abnormalities of structure and function in diabetic myocardium so that this could moderate diabetic myocardial damage and show a cardioprotective effective role of low doses insulin in diabetic mellitus.