南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (11): 1839-1849.doi: 10.12122/j.issn.1673-4254.2023.11.02

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益肺散结丸缓解小鼠癌因性骨骼肌萎缩的作用

吴迎朝，左 谦，罗 薇，王 慧，皮大锦，陈前军，陈利国，林丽珠，欧阳明子   

  1. 广州中医药大学第二临床医学院，广东 广州 510405；广州中医药大学第二附属医院中医证候全国重点实验室，广东 广州 510120；广东省中医院乳腺科，广东 广州 510120；广东省中医药科学院，广东 广州 510120；暨南大学中医学院，广东 广州 510632；广州中医药大学第一附属医院肿瘤中心，广东 广州 510405
  • 出版日期:2023-11-20 发布日期:2023-12-08

Yifei Sanjie Pills alleviates cancer-related skeletal muscle atrophy in mice possibly by lowering inflammatory insulin resistance

WU Yingchao, ZUO Qian, LUO Wei, WANG Hui, PI Dajin, CHEN Qianjun, CHEN Liguo, LIN Lizhu, OUYANG Mingzi   

  1. Second Clinical Medical College of Guangzhou University of Chinese Medicine; State Key Laboratory of Traditional Chinese Medicine Syndrome, Second Affiliated Hospital of Guangzhou University of Chinese Medicine; Department of Breast, Guangdong Provincial Hospital of Chinese Medicine; Guangdong Academy of Traditional Chinese Medicine; College of Traditional Chinese Medicine, Jinan University; Oncology Center, First Affiliated Hospital of Guangzhou University of Chinese Medicine
  • Online:2023-11-20 Published:2023-12-08

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摘要： 目的 研究益肺散结丸对荷瘤小鼠骨骼肌重量、强度、病理形态、糖原和脂质含量以及代谢强度的影响，以探究益肺散结丸治疗荷瘤小鼠骨骼肌萎缩的作用机制。方法 将16只雌性ICR小鼠通过腹腔注射小鼠Lewis肺腺癌细胞建立荷瘤小鼠动物模型，随机分为模型组、益肺散结丸治疗组（4 g·kg-1·d-1，共21 d），8只/组，并设正常组（n=8）。记录小鼠体质量、腓肠肌重量，前肢握力试验测试肌肉强度，液质联用分析益肺散结丸入血成分，酶联免疫吸附测定血清血糖、血清胰岛素浓度和血清及腓肠肌炎症因子水平。苏木素-伊红染色和透射电子显微镜观察腓肠肌病理形态，转录组学测序分析腓肠肌病理过程中涉及的信号通路变化，过碘酸雪夫染色观察腓肠肌糖原含量，油红O染色观察腓肠肌脂质含量，腺苷三磷酸酶染色观察腓肠肌代谢强度，免疫组织化学染色观察腓肠肌炎症细胞浸润程度和P-AKT水平，试剂盒检测腓肠肌肌酸激酶、乳酸脱氢酶和肌红蛋白含量。结果 益肺散结丸增加荷瘤小鼠的骨骼肌强度及腓肠肌重量（P<0.001），降低腓肠肌损伤标志物（P<0.01）。转录组学测序及入血成分显示，益肺散结丸改善荷瘤小鼠腓肠肌损伤的机制可能与炎症浸润、胰岛素抵抗和脂质代谢相关（P<0.05）。实验结果显示，益肺散结丸降低血清和腓肠肌炎症因子水平（P<0.05）及腓肠肌的促炎细胞浸润，增加腓肠肌胰岛素敏感性指标P-AKT水平，提高糖原和脂质含量以及代谢水平。结论 益肺散结丸可能通过降低炎症性胰岛素抵抗缓解癌因性骨骼肌萎缩。

关键词: 益肺散结丸, 炎症性胰岛素抵抗, 癌因性骨骼肌萎缩

Abstract: Objective To evaluate the effects of Yifei Sanjie Pills (YFSJ) on weight, strength, pathology, glycogen and lipid contents and metabolism of skeletal muscles in tumor-bearing mice and explore the therapeutic mechanism of YFSJ for cancer-related skeletal muscle atrophy. Methods Sixteen female ICR mice bearing intraperitoneal Lewis lung adenocarcinoma xenografts were randomized into model group and YFSJ treatment group (daily dose of 4 g/kg for 21 days, n=8), with another 8 normal mice as the normal control group. The changes in body weight and gastrocnemius muscle weight of the mice were recorded. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the drug components in YFSJ entering the blood. Enzyme-linked immunosorbent assay was used to detect serum blood glucose and insulin concentrations and inflammatory cytokine levels in the serum and gastrocnemius. RNA-seq was performed to analyze the signaling pathways involved in the pathologies of the gastrocnemius muscle, and lipid contents in the muscle were observed using Oil red O staining. Adenosine triphosphatase staining was used to assess the metabolic intensity of the gastrocnemius muscle, and inflammatory cell infiltration and P-AKT level were evaluated using immunohistochemical staining; the contents of creatine kinase, lactate dehydrogenase and myoglobin in the gastrocnemius muscle were also detected. Results Treatment with YFSJ significantly increased skeletal muscle strength and gastrocnemius muscle weight (P<0.001) and reduced the levels of gastrocnemius muscle injury markers in the tumor-bearing mice (P<0.01). RNA-seq and LC-MS showed that YFSJ alleviated gastrocnemius muscle injury in the tumor-bearing mice possibly by improving inflammatory infiltration, insulin resistance and lipid metabolism (P<0.05). YFSJ lowered inflammatory cytokine levels in both the serum and gastrocnemius muscle (P<0.05), reduced pro-inflammatory cell infiltration, increased P-AKT level, and improved glycogen and lipid contents and metabolic levels in the gastrocnemius muscle. Conclusion YFSJ alleviates cancer-related skeletal muscle atrophy possibly by reducing inflammatory insulin resistance.

Key words: Yifei Sanjie Pills, inflammatory insulin resistance, cancer-related skeletal muscle atrophy