首页|柔肌顺膵饮改善2型糖尿病骨骼肌胰岛素抵抗的实验研究

柔肌顺膵饮改善2型糖尿病骨骼肌胰岛素抵抗的实验研究

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目的 探讨柔肌顺膵饮对2型糖尿病(T2DM)骨骼肌胰岛素抵抗(IR)的效应及其机制.方法 将40只db/db小鼠按随机数表法分为模型组、柔肌顺膵饮低剂量组、柔肌顺膵饮高剂量组、阳性对照组,每组10只.柔肌顺膵饮低剂量组以157.5 mg·g-1·d-1灌胃,柔肌顺膵饮高剂量组以630 mg·g-1·d-1灌胃,阳性对照组以二甲双胍200 mg·g-1·d-1灌胃.db/dm小鼠10只,作为空白对照组,予同等剂量生理盐水灌胃.各组小鼠每天给药1次,连续给药12周.于给药后6周及12周,测定5组小鼠体重、进食量、饮水量;检测外周血空腹血糖(FBG)、空腹胰岛素(FINS)、血清总胆固醇(TC)、甘油三酯(TG)水平;采用胰岛素抵抗指数(HOMA-IR)评估胰岛素抵抗程度;ELISA法测定外周血炎症因子IL-6、TNF-α及GLUT1、GLUT4.12周后,行口服糖耐量试验(OGTT)及胰岛素耐量试验(ITT)评价小鼠葡萄糖代谢状态,并比较5组骨骼肌组织湿重、GLUT1、GLUT4阳性表达率以及骨骼肌组织病理形态.结果 与空白对照组比较,模型组小鼠的体重、进食量、饮水量、空腹血糖、空腹胰岛素、OGTT各时间点血糖、IL-6、TNF-α、GLUT1、骨骼肌组织GLUT1阳性表达率、HOMA-IR、曲线下面积(AUC)均显著升高(P<0.05),但GLUT4水平、GLUT4阳性表达率、小鼠骨骼肌总湿重均显著降低(P<0.05).与模型组比较,柔肌顺膵饮低、高剂量组及阳性对照组小鼠的进食量、饮水量、空腹血糖和空腹胰岛素、TNF-α、GLUT1水平、AUC、GLUT1阳性表达率、HOMA-IR均显著降低(P<0.05),GLUT4水平、GLUT4阳性表达率和小鼠骨骼肌总湿重均显著升高(P<0.05),且柔肌顺膵饮高剂量组较柔肌顺膵饮低剂量组GLUT4水平、小鼠骨骼肌总湿重升高更明显(P<0.05).柔肌顺膵饮高剂量组HOMA-IR、骨骼肌组织GLUT1阳性表达率较柔肌顺膵饮低剂量组减少更明显(P<0.05).与阳性对照组比较,柔肌顺膵饮低、高剂量组小鼠骨骼肌总湿重均增加(P<0.05).与空白对照组比较,模型组骨骼肌组织呈现不规则多边形凹陷状,肌纤维稀疏,排列紊乱,部分肌细胞见肌溶解现象;柔肌顺膵饮低、高剂量组,骨骼肌组织肌纤维不同程度增加,呈现较规则的多边形团块状,肌细胞异常形态减少,排列较整齐,未见明显的肌细胞溶解现象;阳性药物组肌纤维排列欠规则,可见异常形态的肌细胞.结论 柔肌顺膵饮可以改善T2DM小鼠骨骼肌IR,降低血糖水平,其机制可能与增加骨骼肌湿重,改善骨骼肌病理形态,降低骨骼肌组织GLUT1,升高GLUT4有关.
Experimental research of Rou Ji Shun Cui Yin on skeletal muscle insulin resistance in type 2 diabetes mellitus
Objective To investigate the effect of Rou Ji Shun Cui Yin on insulin resistance in skeletal mus-cle of T2DM and its mechanism.Methods A total of 40 db/db mice were randomly divided into model group,low-dose group,high-dose group and positive control group,with 10 mice in each group.The low-dose group was given 157.5 mg·g-1·d-1 gavage,the high-dose group was given 630 mg·g-1·d-1,and the positive control group was given 200 mg·g-1·d-1 metformin.There were 10 db/dm mice in the blank control group,and the mice were given the same dose of normal saline gavage.Themice in each group wass dosed 1 time per day for 12 weeks.At 6 weeks and 12 weeks after administration,the body weight,food intake and water intake of the mice were monitored.The levels of FBG,FINS,TC and TG in peripheral blood were measured.The degree of insulin resistance was assessed by the insulin resistance index(HOMA-IR).ELISA was used to determine the inflammatory cytokines IL-6 and TNF-α and glu-cose transporters GLUT1 and GLUT4 in peripheral blood.After 12 weeks,oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)were used to evaluate the glucose metabolism of mice.The wet weight of skeletal muscle,the percentage of GLUT1 and GLUT4 positive expression and the pathological changes of skeletal muscle were compared among the 4 groups.Results Compared with the blank control group,the body weight,food intake,water intake,fasting blood glucose,fasting insulin level,OGTT blood glucose,IL-6,TNF-α,GLUT1,the ratio of GLUT1 positive expression in skeletal muscle and HO-MA-IR,the area under the curve were significantly increased in the model group(P<0.05).However,the GLUT4 and the ratio of GLUT4 positive expression and the total wet weight of skeletal muscle in mice were significantly decreased(P<0.05).Compared with the model group,the food intake,water intake,fasting blood glucose and fasting insulin,IL-6,TNF-α,GLUT1,area under the curve,GLUT1positive expression and HOMA-IR ratio in low-dose,high-dose groups and positive control groups were significant-ly decreased(P<0.05).However,GLUT4 and total wet weight of skeletal muscle of mice were signifi-cantly increased(P<0.05),and the increase of GLUT4,GLUT4 postiive expression and total wet weight of skeletal muscle of mice in the high-dose group was more significant than that in the low-dose group(P<0.05).The ratio of HOMA-IR and GLUT1 in skeletal muscle tissue wasdecreased significantly in the high-dose group than in the low-dose group(P<0.05).Compared with the positive control group,the to-tal wet weight of skeletal muscle of the mice in the low and high dose groups was increased(P<0.05).Compared with blank control group,the skeletal muscle tissue in the model group showed irregular polyg-onal depression,sparse muscle fibers,disordered arrangement and myolysis in some myocytes.In the low-dose group and the high-dose group,the muscle fibers of skeletal muscle tissue increased to varying de-grees,showing regular polygonal masses,and the abnormal morphology of muscle cells was reduced,and the arrangement was neat.There was no obvious myolysis.Conclusion By improving skeletal muscle IR,lowering blood sugar and improving T2DM,the mechanism of Rou Ji Shun Cui Yin is related to increasing the wet weight of skeletal muscle,improving the pathological morphology of skeletal muscle,reducing GLUT1 and increasing GLUT4 in skeletal muscle tissue.

Rou Ji Shun Cui Yinskeletal muscleinsulin resistance

蔡之幸、陈越、朱丹阳、陈莉莉

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上海交通大学医学院附属同仁医院中医科,上海 200336

柔肌顺膵饮 骨骼肌 胰岛素抵抗

国家自然科学基金青年科学基金项目陈越长宁区名中医工作室

82205041CNMZY-2021005

2024

新疆医科大学学报
新疆医科大学

新疆医科大学学报

CSTPCD
影响因子:0.76
ISSN:1009-5551
年,卷(期):2024.47(7)