用基因芯片筛选参芪复方保护糖尿病骨骼肌的相关基因

Gene Chip Screening of Related Genes of Shenqi Compound Recipe in Preventing Diabetic Skeletal Muscle Disease

【目的】探讨糖尿病骨骼肌病变与大血管病变的相关性,应用基因芯片技术寻找参芪复方防治糖尿病骨骼肌病变的相关基因。【方法】KKAy小鼠喂饲含有一氧化氮合酶抑制剂L-NAME的饮水和高脂饲料以复制2型糖尿病大血管病变模型。实验分为正常组、KKAy组、模型组、参芪复方组(剂量为14.4 g·kg-1·d-1)、罗格列酮组(剂量为1.33 mg·kg-1·d-1),每组15只。造模同时开始给药,连续8周,期间监测血糖。实验结束后取腹主动脉和骨骼肌,观察病理形态学改变,应用基因芯片技术对参芪复方组—模型组、模型组—KKAy组骨骼肌进行差异基因检测。【结果】参芪复方组可减轻糖尿病大血管病变小鼠骨骼肌细胞萎缩、水肿、断裂和炎症改变。模型组—KKAy组比较筛选出差异表达基因198条,其中上调119条,下调79条。参芪复方组—模型组比较筛选出差异表达基因70条,其中上调33条,下调37条。2个比较组呈逆向表达的差异基因共7条,即Celsr2、Rilpl1、Dlx6as、2010004M13Rik、Anapc13、Gm6097、Ddx39b。【结论】糖尿病骨骼肌病变与大血管病变相关,参芪复方可对糖尿病骨骼肌起保护作用,其机制可能与调控Celsr2、Rilpl1、Dlx6as、2010004M13Rik、Anapc13、Gm6097、Ddx39b基因表达有关。

Objective To investigate the correlation of diabetic skeletal muscle disease with macroangiopathy, and to explore the related genes of Shenqi Compound Recipe （SCR） in preventing and treating diabetic skeletal muscle disease by using gene chip technique, thus to reveal the molecular mechanism. Methods KKAy mice were fed with water containing nitri oxide synthase inhibitor of Nω-nitro-L-arginine methyl ester （ L-NAME） and high fat diet to induce the macroangiopathy complicated with type 2 diabetes. The experimental animals were divided into normal c57BL/GJ group, KKAy group, model group, SCR group （in the dosage of 14.4 g·kg^-1·d^-1） and rosiglitazone group （ in the dosage of 1.33 mg·kg^-1·d^-1） , 15 in each group. The medication groups were administered the corresponding agents for 8 consecutive weeks just as the modeling began. During the experiment period, blood glucose was monitored. At the end of the experiment, the abdominal aorta and skeletal muscle of mice were taken out for the observation of morphological changes, and differentially expressed genes of skeletal muscle between SCR group and model group, and between model group and KKAy group were detected by gene chip technique. Results SCR had an effect on relieving the atrophy, edema, fracture, and inflammatory changes in the skeletal muscle. There were 198 genes differentially expressed between model group and KKAy group, including 119 up-regulated genes and 79 down-regulated genes. There were 70 genes differentially expressed between SCR group and model group, including 33 up-regulated genes and 37 down-regulated genes. In the two comparison groups, 7 genes （ Celsr2, Rilpl1, Dlx6as, 2010004M13Rik, Anapc13, Gm6097, Ddx39b） showed reversed differential expression. Conclusion Diabetic skeletal muscle disease is associated with macroangiopathy. SCR has preventive effect on diabetic skeletal muscle lesion, and the mechanism may be related to the regulation of Celsr2, Rilpl1, Dlx6as, 2010004M13Rik, Anapc13, Gm6097, Ddx39b gene expression.