实验性1型糖尿病树鼩肌组织对GLUT4、PI3K和UCP3的表达

EXPRESSION FOR PI3K,GLUT4 AND UCP3 IN SKELETAL MUSCLE OF EXPERIMENTAL DIABETIC TREE SHREW

目的:探讨实验性1型糖尿病树骨骼肌组织对葡萄糖转运体4(GLUT4)、磷脂酰肌醇3激酶(PI3K)调节亚基p85α(PI3K-p85α)和解偶联蛋白3(UCP3)表达的变化。方法:将26只树随机分为正常对照组8只,糖尿病诱导组(以链脲佐菌素诱导)18只。实验历时6周。微量血糖仪检测静脉空腹血糖(FBG),血糖≥11.1mmol/L定为糖尿病成模。实验结束时取右侧股二头肌标本,在光镜和透射电镜下观察肌组织形态学改变,以免疫组化法检测肌组织中GLUT4、p85α和UCP3的表达。结果:1糖尿病组肌纤维普遍萎缩,肌纤维横截面积仅为正常对照的65.7%。超微病变主要表现为灶性肌丝溶解和肌质膜大范围锯齿状突起,部分线粒体嵴断裂、基质溶解或空泡形成。肌组织中的微血管内皮增厚、管腔狭窄、变形;2糖尿病组肌组织对p85α的表达无明显改变(P>0.05),而GLUT4和UCP3的表达水平均明显低于正常对照组(P<0.05)。结论:糖尿病树骨骼肌组织对GLUT4和UCP3的表达明显受损。代谢紊乱和糖尿病肌病可能是引起糖尿病树骨骼肌表达GLUT4和UCP3下调的重要原因。

Objective:To evaluate changes of the expression for PI3K-p85α(phosphatidylinositol-3 kinase regulated subunit p85α, PI3K-p85α),GLUT4 (glucose transporter 4 ,GLUT4) and CUP3(uncoupling protein 3, UCP3) in skeletal muscles of experimental diabetic tree shrews.Methods:Type 1 diabetes mellitus in tree shrews were induced by STZ (streptozotocin, STZ) intravenously. The animals were monitored for diabetes by measurement of fasting blood glucose (FBG) levels with a one-step glucometer. Animals were considered diabetic when FBG were ≥11.1 mmol/L.In the end of the experiment all animals were executed and the samples of biceps femoris muscles were removed and preserved for subsequent use. Morphological changes of musculature was evaluated by light and electronic microscopy. The content for PI3K-p85, GLUT4 and UCP3 were measured by immunohistochemistry.Result:①Myatrophy was shown significantly in the diabbtic amimals under light microscope and dispersed disruption of myofilament was observed under microscopy. Mitochondrial swelling and lysis of mitochondrial cristae were evidenced and sarcolemmal exhibited rampart-or serrate prominency in all diabetic animals. Capillary in the musculature exhibited luminal narrowing and distortion.②Immunohistochemical analysis: the levels of expression for p85α in skeletal muscle did not differ between the diabetic group and the controls whereas GLUT4 and UCP3 decreased significantly in the diabetic group compared to the control one (all P<0.05).Conclusion:Musculature decreased expression for GLUT4 and UCP3 may likely be a consequence of the ability of metabolic disorder to result in diabetic myopathy in experimental type 1 diabetes mellitus of tree shrews.