首页|金水六君煎通过上调PRMT1调控PRMT6-FOXO3轴减轻COPD小鼠骨骼肌萎缩实验研究

金水六君煎通过上调PRMT1调控PRMT6-FOXO3轴减轻COPD小鼠骨骼肌萎缩实验研究

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目的:观察金水六君煎通过上调PRMT1调控PRMT6-FOXO3轴减轻COPD小鼠骨骼肌萎缩的机制。方法:选取25只SPF级5~6周龄雄性ICR小鼠,随机分为空白对照组、模型对照组、中药组、Prmt1-siRNA、Prmt1-siRNA+中药组,用烟熏和内毒素注射建立动物模型,通过比较肌张力、透射电镜判断金水六君煎对肌肉的改善功能,蛋白免疫印迹法检测肌肉组织中PRMT1、PRMT6、FOXO3蛋白表达,实时荧光定量聚合酶链式反应检测PRMT1、PRMT6、FOXO3 mRNA表达水平。结果:与空白组比较,模型组小鼠肌张力明显增加(P<0。05)、小鼠右趾长伸肌纤维带状分布略微紊乱,脂滴数量增多,线粒体肿胀变形,线粒体内存在空泡,模型组Prmt1蛋白表达降低(P<0。05),而PRMT6、FOXO3蛋白表达升高(P<0。05);Prmt1 mRNA表达降低(P<0。05),而PRMT6、FOXO3 mRNA表达升高(P<0。05)。与模型组比较,中药组肌张力明显降低(P<0。05);右趾长伸肌纤维带状排列整理,脂滴数量减少,线粒体形态正常;中药组Prmt1蛋白表达升高(P<0。05),而PRMT6、FOXO3蛋白表达降低(P<0。05);Prmt1 mRNA表达升高(P<0。05),而PRMT6、FOXO3 mRNA表达降低(P<0。05);与模型组比较,Prmt1-siRNA组肌张力无明显差异;Prmt1-siRNA组小鼠右趾长伸肌纤维带状分布更紊乱,脂滴数量增多,线粒体内空泡增多;Prmt1-siRNA组Prmt1蛋白表达降低(P<0。05),而PRMT6、FOXO3蛋白表达升高(P<0。05);Prmt1-siRNA组Prmt1 mRNA表达降低(P<0。05),而PRMT6、FOXO3mRNA表达升高(P<0。05);与Prmt1-siRNA组比较,Prmt1-siRNA+中药组肌张力明显降低(P<0。05);Prmt1-siRNA+中药组右趾长伸肌脂滴数量减少,线粒体较为形态正常;Prmt1-siRNA+中药组Prmt1蛋白表达升高(P<0。05),而PRMT6、FOXO3蛋白表达降低(P<0。05);Prmt1-siRNA+中药组Prmt1 mRNA表达升高(P<0。05),而PRMT6、FOXO3 mRNA表达降低(P<0。05)。结论:金水六君煎通过上调Prmt1调控PRMT6-FOXO3轴抑制COPD小鼠骨骼肌萎缩。
Approach to Jinshui Liujun decoction reducing skeletal muscle atrophy of COPD mice by up-regulating PRMT1 to regulate and control PRMT6-FOXO3 axis
Objective:To approach the mechanism of Jinshui Liujun decoction reducing skeletal muscle atrophy of COPD mice by up-regulating PRMT1 to regulate and control PRMT6-FOXO3 axis.Methods:25 SPF male ICR mice aged 5-6 weeks were selected and randomly divided into blank control group,model control group,TCM group,Prmt1-siRNA group and Prmt1-siRNA and TCM group.The animal model was established by smoking and endotoxin injection.By comparing muscular tension and transmission electron microscopy,it was judged that Jinshui Liujun decoction improved the muscle function.The expressions of PRMT1,PRMT6 and FOXO3 proteins in muscle tissue were detected by Western blot.The level of expressions of PRMT1,PRMT6 and FOXO3 mRNA was detected by real-time fluorescence quantitative polymerase chain reaction.Results:Compared with the blank group,the muscle tension of mice in the model group was significantly increased(P<0.05);the banded distribution of right extensor digitorum longus fiber of mice was slightly disordered;the number of lipid droplets was increased;the mitochondria were swollen and deformed,and there were vacuoles in mitochondria;the expression of Prmt1 protein in the model group was decreased(P<0.05),while the expressions of PRMT6 and FOXO3 protein were increased(P<0.05);the expression of Prmt1 mRNA in the model group was decreased(P<0.05),while the expressions of PRMT6 and FOXO3 mRNA were increased(P<0.05).Compared with the model group,the muscle tension of TCM group was significantly decreased(P<0.05);the banded arrangement of right extensor digitorum longus fibers was orderly;the number of lipid droplets was decreased;the mitochondrial morphology was normal;the expression of Prmt1 protein of TCM group was increased(P<0.05),while the expressions of PRMT6 and FOXO3 protein were decreased(P<0.05);the expression of Prmt1 mRNA of TCM group was increased(P<0.05),while the expressions of PRMT6 and FOXO3 mRNA were decreased(P<0.05).Compared with the model group,the muscle tension of Prmt1-siRNA group was without significant difference;in Prmt1-siRNA group,the banded distribution of right extensor digitorum longus fibers was more disorderly,the number of lipid droplets was increased,the vacuoles in mitochondria were increased;the expression of Prmt1 protein of Prmt1-siRNA group was decreased(P<0.05),while the expressions of PRMT6 and FOXO3 protein was increased(P<0.05);the expression of Prmt1 mRNA of Prmt1-siRNA group was decreased(P<0.05),while the expressions of PRMT6 and FOXO3 mRNA was increased(P<0.05).Compared with Prmt1-siRNA group,the muscle tension of Prmt1-siRNA and TCM group was significantly decreased(P<0.05);the number of lipid droplets of right extensor digitorum longus of Prmt1-siRNA and TCM group was decreased;the mitochondria morphology was relatively normal;the expression of Prmt1 protein of Prmtl-siRNA and TCM group was increased(P<0.05),while the expressions of PRMT6 and FOXO3 protein was decreased(P<0.05);the expression of Prmt1 mRNA of Prmt1-siRNA and TCM group was increased(P<0.05),while the expressions of PRMT6 and FOXO3 mRNA were decreased(P<0.05).Conclusion:Jinshui Liujun decoction can inhibit skeletal muscle atrophy of COPD mice by up-regulating Prmt1 to regulate and control PRMT6-FOXO3 axis.

COPDJinshui Liujun decoctionskeletal muscle atrophyautophagyexperimental researchtherapy of TCM

游进顺、张川林、陈可强、王琪

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福建中医药大学附属第二人民医院(福州350003)

慢性阻塞性肺疾病 金水六君煎 自噬 实验研究

2024

山西中医
山西省中医药学会 山西中医药研究院

山西中医

影响因子:0.59
ISSN:1000-7156
年,卷(期):2024.40(6)