健脾益肾方对肺癌恶病质模型小鼠肌肉消耗及生存期的影响及机制研究
Effect and mechanism of Jianpi Yishen Formula on muscle consumption and survival time in mouse model with lung cancer cachexia
- 北京中医药 2023年42卷第11期 页码：1212-1218
- 作者机构：
1.中国中医科学院广安门医院血液科，北京 100053
2.中国中医科学院中医临床基础医学研究所， 北京 100091
3.中国中医科学院针灸研究所，北京 100091
- 作者简介：
吉兆奕，女，39岁，硕士，主治医师。研究方向：中西医结合防治肿瘤与血液疾病。
吴洁，E-mail：wujielily@163.com
- 基金信息：国家自然科学基金资助项目(81373596);北京市自然科学基金资助项目(7142141)
DOI：10.16025/j.1674-1307.2023.11.011
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吉兆奕，朱健，朱晓云，等.健脾益肾方对肺癌恶病质小鼠模型肌肉消耗及生存期的影响及机制研究［J］.北京中医药，2023，42（11）：1212-1218.
JI Zhao-yi,ZHU Jian,ZHU Xiao-yun,et al.Effect and mechanism of Jianpi Yishen Formula on muscle consumption and survival time in mouse model with lung cancer cachexia[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(11):1212-1218.
吉兆奕，朱健，朱晓云，等.健脾益肾方对肺癌恶病质小鼠模型肌肉消耗及生存期的影响及机制研究［J］.北京中医药，2023，42（11）：1212-1218. DOI： 10.16025/j.1674-1307.2023.11.011.
JI Zhao-yi,ZHU Jian,ZHU Xiao-yun,et al.Effect and mechanism of Jianpi Yishen Formula on muscle consumption and survival time in mouse model with lung cancer cachexia[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(11):1212-1218. DOI： 10.16025/j.1674-1307.2023.11.011.
摘要
目的,2,建立C57小鼠肺癌恶病质模型，观察健脾益肾方对其肌肉消耗及生存期的影响，并探讨其可能的作用机制。,方法,2,取10只C57BL/6小鼠为正常对照组；剩余小鼠给予腋下注射lewis肺腺癌肿瘤细胞制备肺癌恶病质模型，随机分为模型组、健脾益肾组、甲地孕酮组，各16只。肺癌细胞接种第2天，健脾益肾组以5倍临床等效剂量给予2.3 g/mL健脾益肾方灌胃，0.3 mL/次；甲地孕酮组给予甲地孕酮溶液灌胃，0.3 mL/次；模型组与正常对照组给予同等体积的生理盐水灌胃。各组均1次/d，灌胃直至第60天。给药14 d后每组取10只小鼠以断颈法处死，其余小鼠留存进行生存期观察。对比各组生化指标［白蛋白（ALB）、球蛋白（GLB）、白球比（ALB/GLB），谷丙转氨酶（ALT）、谷草转氨酶（AST），血糖（GLU），血钙（CA）］，脾脏、肝脏质量及腓肠肌质量，血清TNF-α、激活素A（Activin-A）水平，生存期，肌萎缩相关基因（Activin-A、Myostatin、MuRF-1 mRNA）表达，自噬相关基因（AMPK、beclin mRNA）表达。,结果,2,各组体质量比较，差异无统计学意义（,P,>,0.05）。与模型组比较，健脾益肾组、甲地孕酮组肿瘤最大径、瘤重小（,P,<,0.05），且健脾益肾组肿瘤最大径、瘤重小于甲地孕酮组（,P,<,0.05）。与正常对照组比较，模型组GLU、ALB、ALB/GLB低，AST、AST/ALT、CA高（,P,<,0.05）；与模型组比较，健脾益肾组GLU、ALB、ALB/GLB高，AST、AST/ALT、CA低（,P,<,0.05），甲地孕酮组GLU高（,P,<,0.05）；与甲地孕酮组比较，健脾益肾组ALB/GLB高（,P,<,0.05）。与正常对照组比较，模型组脾脏、肝脏质量高，腓肠肌质量低（,P,<,0.05）；与模型组比较，健脾益肾组肝脏质量低（,P,<,0.05），腓肠肌质量高（,P,<,0.05）；与甲地孕酮组比较，健脾益肾组肝脏质量低（,P,<,0.05）。与正常对照组比较，模型组血清TNF-α、Activin-A水平高（,P,<,0.05）；与模型组比较，健脾益肾组、甲地孕酮组血清Activin-A水平低（,P,<,0.05）。与模型组比较，健脾益肾组生存期长（,P,<,0.05）；与模型组比较，甲地孕酮组生存期长，但差异无统计学意义（,P>,0.05）；与甲地孕酮组比较，健脾益肾组生存期长，但差异无统计学意义（,P>,0.05）。与正常对照组比较，模型组Activin-A、Myostatin、MuRF-1 mRNA表达高（,P,<,0.05）；与模型组比较，健脾益肾组、甲地孕酮组Activin-A、Myostatin、MuRF-1 mRNA表达低（,P,<,0.05）；与甲地孕酮组比较，健脾益肾组Activin-A mRNA表达低（,P,<,0.05）。与正常对照组比较，模型组AMPK、beclin mRNA表达高（,P,<,0.05）；与模型组比较，健脾益肾组、甲地孕酮组AMPK、beclin mRNA表达低（,P,<,0.05）；与甲地孕酮组比较，健脾益肾组AMPK mRNA表达低（,P,<,0.05），beclin mRNA表达高（,P,<,0.05）。,结论,2,健脾益肾方能够改善肺癌恶病质小鼠体内炎症环境，抑制其骨骼肌萎缩，延长生存期；其作用机制可能与自噬-溶酶体途径（autophagy-lysosomal pathway，ALS）和泛素-蛋白酶体（ubiquitin-proteasome，UPS）信号途径有关。
Abstract
Objective,2,To establish a model of cachexia of lung cancer in C57 mice and observe the mechanism of Jianpi Yishen（strenghtening spleen and benefiting kidney）Formula on muscle consumption and the survival time of cachexia of lung cancer in order to explore the mechanism.,Methods,2,Ten C57BL/6 mice were randomly selected as normal control group； lewis lung adenocarcinoma tumor cells were injected subcutively into the armpit of C57BL/6 mice to establish tumor cachexia models， which were divided into model group，Jianpi Yishen group and megestrol acetate group of 16 mice in each group.On the second day after the inoculation of lung cancer cells， the Jianpi Yishen group was given 2.3 g/mL Jianpi Yishen recipe by gavage， 0.3 mL/ time， at 5 times the clinical equivalent dose； Megestrol acetate group was given megestrol acetate solution by gavage， 0.3 mL/ time； the model group and the normal control group were given the same volume of normal saline by gavage.Each group was given intragastric administration once a day until the 60th day.After 14 days of administration， 10 mice in each group were killed by neck-breaking， and the remaining mice were kept for survival observation. Biochemical indexes（ALB， GLB，ALB/GLB， ALT， AST，GLU， CA）， Spleen， liver and gastrocnemius mass， serum levels of TNF-α and Activin-A， as well as Activin-A，Myostatin，MuRF-1 mRNA，and expression of AMPK， beclin mRNA were detected.,Results,2,There was no significant difference in body mass among groups （,P,>,0.05）.Compared with the model group， the largest tumor diameter and tumor weight in Jianpi Yishen group and Megestrol acetate group were smaller （,P,<,0.05）， and the largest tumor diameter and tumor weight in Jianpi Yishen group were smaller than those in Megestrol acetate group （,P,<,0.05）. Compared with the normal control group， GLU， ALB and ALB/GLB in the model group were lower， while AST， AST/ALT and CA were higher （,P,<,0.05）. Compared with model group， GLU， ALB， ALB/GLB in Jianpi Yishen group were higher， AST， AST/ALT and CA were lower （,P,<,0.05）， and GLU in Megestrol acetate group was higher （,P,<,0.05）. Compared with megestrol acetate group， the ALB/GLB of Jianpi Yishen group was higher （,P,<,0.05）. Compared with the normal control group， the weight of spleen and liver in the model group was higher， but the weight of gastrocnemius was lower （,P,<,0.05）. Compared with the model group， the quality of liver was lower （,P<,0.05） and the quality of gastrocnemius was higher （,P,<,0.05）. Compared with megestrol acetate group， the quality of liver in Jianpi Yishen group was lower （,P,<,0.05）. Compared with the normal control group， the levels of serum TNF-α and Activin-A in the model group were higher （,P,<,0.05）. Compared with the model group， the serum Activin-A levels in the Jianpi Yishen group and Megestrol acetate group were lower （,P,<,0.05）. Compared with the model group， the survival time of Jianpi Yishen group was longer （,P,<,0.05）. Compared with the model group， the survival time of megestrol acetate group was longer， but the difference was not statistically significant （,P,>,0.05）. Compared with megestrol acetate group， the survival time of Jianpi Yishen group was longer， but the difference was not statistically significant （,P,>,0.05）. Compared with the normal control group， the mRNA expressions of Activin-A， Myostatin and MuRF-1 mRNA the model group were higher （,P,<,0.05）. Compared with the model group， the expressions of Activin-A， Myostatin and MuRF-1 mRNA in the Jianpi Yishen group and Megestrol acetate group were lower （,P,<,0.05）. Compared with megestrol acetate group， the expression of Activin-A mRNA in Jianpi Yishen group was lower （,P,<,0.05）. Compared with the normal control group， the expression of AMPK and beclin mRNA in the model group was higher （,P ,<, 0.05）. Compared with the model group， the expressions of AMPK and beclin mRNA in Jianpi Yishen group and Megestrol acetate group were lower （,P,<, 0.05）. Compared with megestrol acetate group， the expression of AMPK mRNA in Jianpi Yishen group was lower （,P,<,0.05） and beclin mRNA was higher （,P,<,0.05）,Conclusion,2,Jianpi Yishen Formula can improve the inflammatory environment，inhibit skeletal muscle atrophy in mice with lung cancer exoxia and prolong the lifeby regulating the autophagolysosome pathway （ALS） and ubiquitin-proteasome pathway （UPS）.
关键词
肺肿瘤小鼠Lewis细胞肿瘤恶病质自噬-溶酶体途径泛素-蛋白酶体系统健脾益肾方
Keywords
Lung tumormiceLewis cellstumor cachexiaautophagy-lysosomal pathway （ALS） and ubiquitin-proteasome （UPS）Jianpi Yishen Formula
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