健脾清化颗粒改善镉暴露大鼠骨骼肌胰岛素抵抗的作用和机制  

The effect and mechanism of Jianpi Qinghua granule in improving skeletal muscle insulin resistance induced by cadmium exposure in rats

作　　者：陈驰 陈媛 王宁荐[3] 徐隽斐[1] 韩煦 肖岩岩 田静 王超[1] 蔡梦洁 陈清光[4] 陆灏[1] Chen Chi;Chen Yuan;Wang Ningjian;Xu Junfei;Han Xu;Xiao Yanyan;Tian Jing;Wang Chao;Cai Mengjie;Chen Qingguang;Lu Hao(Department of Endocrinology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Traditional Chinese Medicine,Henan Provincial People's Hospital,Zhengzhou 450000,China;Department of Endocrinology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 20001l,China;Diabetes Research Institute,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院内分泌科,201203 [2]河南省人民医院中医科,郑州450000 [3]上海交通大学医学院附属第九人民医院内分泌科,200011 [4]上海中医药大学附属曙光医院糖尿病研究所,201203

出　　处：《中华内分泌代谢杂志》2025年第1期54-60,共7页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金(82100846,82405250,82474398);上海市科委扬帆计划(20YF1423500);上海市中医临床重点实验室(20DZ2272200);上海市医苑新星青年医学人才培养资助计划(沪卫人事(2024)70号)。

摘　　要：目的探讨健脾清化颗粒改善长期低剂量镉暴露大鼠骨骼肌胰岛素抵抗的作用及机制。方法选取24只SPF级健康2月龄Sprague-Dawley大鼠,分为正常对照组(NC组)、镉暴露组(Cd组)和健脾清化颗粒保护组(Cd+JPQHG组)。24周后检测各组大鼠空腹血糖及胰岛素并计算稳态模型评估的胰岛素抵抗指数(HOMA-IR),腹腔葡萄糖耐量试验和胰岛素耐量试验评估胰岛素敏感性。同时提取骨骼肌组织,Western印迹法检测胰岛素信号通路相关蛋白水平,免疫荧光检测葡萄糖转运蛋白4(GLUT4)转位情况,并测定氧化应激指标。结果与NC组相比,Cd组24周后大鼠空腹血糖、胰岛素和HOMA-IR水平显著升高,出现糖耐量和胰岛素耐量异常;而健脾清化颗粒干预12周可显著改善糖代谢、减轻糖耐量和胰岛素耐量异常。Western印迹结果显示,与NC组相比,Cd组骨骼肌磷脂酰肌醇3-激酶(PI3K)及蛋白激酶B(Akt)磷酸化水平显著降低,而Cd+JPQHG组则较Cd组显著升高,且GLUT4向细胞膜转位增加。与此同时,镉暴露显著升高过氧化氢(H2O2)和丙二醛,降低抗氧化酶活力,而健脾清化颗粒干预后氧化应激水平明显改善(P<0.05)。结论健脾清化颗粒可能通过改善氧化应激调节胰岛素信号通路关键蛋白的磷酸化水平、促进GLUT4向细胞膜转位,从而改善长期低剂量镉暴露导致的骨骼肌胰岛素抵抗和糖代谢紊乱。Objective:To investigate the effect and mechanism of Jianpi Qinghua granule in improving skeletal muscle insulin resistance induced by long-term low-dose cadmium exposure in rats.Methods:A total of 24 SPF-grade healthy 2-month-old Sprague-Dawley rats were assigned to normal control(NC)group,cadmium exposure(Cd)group,and Jianpi Qinghua granule protection(Cd+JPQHG)group.After 24 weeks,fasting blood glucose and insulin levels were measured,and HOMA-IR was calculated.The intraperitoneal glucose tolerance test and insulin tolerance test were conducted to assess insulin sensitivity.Skeletal muscle tissues were extracted for Western blot analysis to detect levels of insulin signaling pathway-related proteins.Immunofluorescence was used to assess the translocation of glucose transporter 4(GLUT4),and oxidative stress markers were measured.Results:Compared to the NC group,the Cd group showed significant increases in fasting plasma glucose,fasting insulin levels,and HOMA-IR after 24-week exposure.Abnormal glucose and insulin tolerance were also observed in the Cd group.The 12-week intervention with Jianpi Qinghua granule significantly improved glucose metabolism and alleviated the abnormalities in glucose and insulin tolerance.Western blot results indicated that the phosphorylation levels of PI3K and Akt in the skeletal muscle of the Cd group were significantly reduced compared to the NC group,while these levels were significantly elevated in the Cd+JPQHG group,along with increased translocation of GLUT4 to the cell membrane.Additionally,cadmium exposure significantly increased H 2O 2 and malondialdehyde levels while decreased antioxidant enzyme activity.These oxidative stress indicators improved significantly after Jianpi Qinghua granule intervention(P<0.05).Conclusion:Jianpi Qinghua granule may improve skeletal muscle insulin resistance and glucose metabolism disorders due to long-term low-dose cadmium exposure by reducing oxidative stress,regulating the phosphorylation levels of key proteins in the insulin signaling path

关 键 词：糖尿病 胰岛素抵抗 镉 健脾清化颗粒 氧化应激 

分 类 号：R285.5[医药卫生—中药学]