摘要
目的探讨1型糖尿病(T1DM)树鼩骨骼肌病变的发病机制。方法正常对照组(A组,n=8);STZ糖尿病成模组9只(B组),糖尿病未成模组5只(C组)。在光镜和透射电镜下观察股二头肌形态学变化,以免疫组化法检测肌组织中细胞凋亡相关分子Bcl2、Fas、FasL、caspase1和caspase3的表达。结果B组肌纤维普遍萎缩,肌纤维横截面积明显小于A组(2.49±0.47μm2vs3.79±0.40μm2,P<0.05)电镜下B组肌组织呈灶性肌丝溶解,肌质膜呈锯齿状突起,部分线粒体嵴断裂、基质溶解或空泡化。肌膜下线粒体密集成群、排列紊乱和形态异常。肌细胞核异染色质增多并呈块状边集。肌组织微血管内皮伸出许多伪足,内皮增厚、管腔狭窄。微血管基底膜无明显增厚。B组肌组织对Bcl2、Fas/FasL和caspase3均呈阳性表达,A组和C组仅对FasL呈弱阳性表达。结论骨骼肌纤维普遍性萎缩、灶性肌丝溶解、肌质膜异常突起和线粒体损伤是T1DM树鼩骨骼肌病变的主要特征,骨骼肌组织中细胞凋亡通路激活可能是糖尿病肌病的重要原因。
To evaluate the morphometric characteristics and the pathogenesis of diabetic myopathy in experimental type 1 diabetes mellitus of tree shrews. Methods Tree shrews were assigned to normal control （group A, n=8） and STZ-modeled diabetes （FBG≥11. 1 mmol/L, group B, n=9）. and STZ-modeled non-diabetes group （FBG＜11.1 mmol/L, group C, n=5）. At the end of six weeks of the experiment, the morphological changes of samples of biceps femoris muscles were evaluated by light and electron microscopy. The gene expressions of Bcl-2, Fas, FasL, caspase 1 and caspase 3 in musculature were measured by immunohistochemistry. Results The cross section area was smaller in group B than that in group A （2.49±0.47 μm^2 vs 3.79±0.40 μm^2 , P＜0.05）. Dispersed disruption of myofilament, lysis of mitochondrial cristae, vacuolization and deformation of mitochondrium in group B were evidenced. Myocytic nuclei showing increased heterochromatin and chromatin margination were seen. Sarcolemma exhibited serrated prominency. Thickened capillary endothelium formed digitation accompanied by luminal narrowing. There were the moderate expressions of Bcl-2,Fas/ FasL, and caspase 3, but not of caspase 1 within the musculature of diabetic model. Conclusion Morphometric changes of skeletal muscle in experimental DM of tree shrews are characterized primarily by widespread myotrophy and scattered myofilament lysis that may in part result from a decreased level of blood insulin and muscular microangiopathy and the activation of apoptotic pathway.
基金
广西壮族自治区科委科研基金资助项目(0135024)
