补阳还五汤防治2型糖尿病小鼠骨骼肌病变的作用  

Effect of Buyang Huanwutang on Skeletal Muscle Injuries in Mouse Model of Type 2 Diabetes Mellitus

作　　者：王杨 姜立娟 崔巍 张文风[1] 魏岩 WANG Yang;JIANG Lijuan;CUI Wei;ZHANG Wenfeng;WEI Yan(School of Basic Medicine,Changchun University of Chinese Medicine,Changchun 130117,China)

机构地区：[1]长春中医药大学基础医学院,长春130117

出　　处：《中国实验方剂学杂志》2024年第14期10-16,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：吉林省教育厅科学技术研究项目(JJKH20230963KJ,JJKH20241054KJ,JJKH20241056KJ);通化市医药健康产业发展专项资金项目(20210404005TH);2023年吉林省名老中医专家传承工作室建设项目。

摘　　要：目的:基于线粒体转运、糖代谢、氧化应激及炎性介质探讨补阳还五汤防治2型糖尿病骨骼肌病变的作用。方法:选用60只SPF级雄性C57BL/6J小鼠,高脂饲料联合链脲佐菌素腹腔注射构建2型糖尿病小鼠模型,按随机数字表法随机分组,其中正常组、补阳还五汤高、中、低剂量组、二甲双胍组、模型组各10只。补阳还五汤各剂量组及二甲双胍组灌喂剂量分别为86.5、43.2、21.6 g·kg^(-)1、150 mg·kg^(-1);实验期间定期检测小鼠血糖等指标,实验结束后取骨骼肌,分别置于4%多聚甲醛-80℃冰箱冻存。进行血液样本送检,骨骼肌采用苏木素-伊红(HE)染色,酶联免疫吸附测定法(ELISA)检测炎症指标及活性氧(ROS),蛋白免疫印迹法(Western blot)、免疫组化检测线粒体蛋白表达情况。结果:与正常组比较,模型组小鼠空腹血糖、饮水量、进食量显著升高(P<0.01),体质量显著降低(P<0.01),与模型组比较,补阳还五汤组及二甲双胍组小鼠空腹血糖、进水量、进食量明显降低(P<0.05,P<0.01),体质量上升(P<0.01);与正常组比较,模型组TNF-α、IL-6、ROS显著增加(P<0.01),与模型组比较,二甲双胍组与补阳还五汤各组TNF-α、IL-6、ROS均明显下降(P<0.05,P<0.01)。模型组骨骼肌肌纤维普遍萎缩性变细,提示骨骼肌萎缩,形态结构改变,而二甲双胍组及补阳还五汤各组小鼠骨骼肌病理状态有所减轻,纤维束形态部分恢复正常;与正常组比较,模型组线粒体融合蛋2(Mfn2)显著减少(P<0.01),与模型组比较,二甲双胍组与补阳还五汤各剂量组Mfn2明显增多(P<0.05,P<0.01);与正常组比较,模型组分裂蛋白Drp1显著增多(P<0.01),与模型组比较,二甲双胍组与补阳还五汤各剂量组分裂蛋白1(Drp1)显著减少(P<0.01)。结论:补阳还五汤可以改善2型糖尿病骨骼肌病变小鼠的体质量及骨骼肌病理形态,降低空腹血糖、进食量、进水量、TNF-α、IL-6、ROS值及分裂蛋白Drp1,升�Objective:To study the effects of Buyang Huanwutang on the skeletal muscle injuries in type 2 diabetes mellitus from mitochondrial transport,glucose metabolism,oxidative stress,and inflammation.Method:A total of 60 SPF-grade male C57BL/6J mice were selected in this study.The mouse model of type 2 diabetes mellitus was established with a high-fat diet combined with intraperitoneal injection of streptozotocin.The mice were assigned by the random number table method into blank control,model,high-,medium-,and low-dose(86.5,43.2,21.6 g·kg^(-1),respectively)Buyang Huanwutang,and metformin(150 mg·kg^(-1))groups,10 mice in each group.During the experiment period,blood glucose and other indicators of mice were measured regularly.At the end of the experiment,skeletal muscle samples were collected and frozen in 4%paraformaldehyde and-80℃,respectively.Blood samples were sent for examination.The skeletal muscle was stained with hematoxylin-eosin.The levels of inflammation indicators and reactive oxygen species(ROS)were determined by enzyme-linked immunosorbent assay.The expression of mitochondrial proteins was determined by Western blot and immunohistochemistry.Result:Compared with the blank control group,the model group showcased increased fasting blood glucose,water intake,and food intake(P<0.01)and decreased body weight(P<0.01).Compared with the model group,metformin and Buyang Huanwutang reduced the fasting blood glucose,water intake,and food intake(P<0.05,P<0.01)and increased the body weight(P<0.01).Compared with the blank control group,the model group showed rising levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and ROS(P<0.01),which were decreased by metformin and Buyang Huanwutang(P<0.05,P<0.01).The skeletal muscle fibers in the model group were generally atrophic and thin,which suggested atrophy and morphological changes of the skeletal muscle,while metformin and Buyang Huanwutang alleviated the pathological changes of the skeletal muscle and restored the morphology of fiber bundles.Compared wit

关 键 词：补阳还五汤 2型糖尿病 骨骼肌 线粒体 线粒体融合蛋2(Mfn2) 分裂蛋白1(Drp1) 

分 类 号：R2-0[医药卫生—中医学] R22R285.5R289R33