保元解毒汤对癌性恶病质小鼠骨骼肌蛋白质降解及MAFbx、MuRF-1基因表达的影响

Effects of Baoyuan Jiedu Decoction on the skeletal muscle protein degradation of cancer cachexia model mice and the expression of MAFbx and MuRF-1 mRNA

目的研究保元解毒汤对肺癌恶病质小鼠骨骼肌蛋白质降解及MAFbx、MuRF-1基因表达的影响,探讨其干预骨骼肌蛋白质代谢的可能机制。方法 C57BL/6小鼠皮下接种Lewis肺癌细胞株复制肺癌恶病质小鼠模型。40只小鼠随机分为正常对照组、模型组、保元解毒汤组和醋酸甲羟孕酮组。测定小鼠腓肠肌质量;高效液相色谱法检测腓肠肌3-甲基组氨酸(3-MH)含量;RT-PCR法测定腓肠肌MAFbx、MuRF-1mRNA表达。结果与正常对照组比较,模型组小鼠腓肠肌质量显著降低(P<0.05),肌组织内3-MH含量明显升高(P<0.05),MAFbx、MuRF-1 mRNA表达显著升高(P<0.05);与模型组和醋酸甲羟孕酮组比较,保元解毒汤组小鼠腓肠肌质量显著增加(P<0.05),肌组织内3-MH含量明显降低(P<0.05),MAFbx、MuRF-1 mRNA表达显著降低(P<0.05)。结论保元解毒汤能够改善癌性恶病质小鼠骨骼肌萎缩,其机制可能与MAFbx、MuRF-1基因表达下调,骨骼肌收缩蛋白降解减少相关。

Objective To study Baoyuan Jiedu Decoctiong effects on the skeletal muscle protein degradation and the expression of MAFbx and MuRF - 1 mRNA of lung cancer cachexia mice, to explore the possible mechanism of Baoyuan Jiedu Decoctiong inter- vening the skeletal muscle protein degradation. Methods Mouse models of lung cancer cachexia were established after the hypo- dermic inoculation of Lewis lung cancer cells to C57BL/6 mouse. 40 miee were divided into normal control group, model control group, Baoyuan Jiedu Decoction group and medroxyprogesterone acetate group （n = 10） randomly. The mouse gastroenemius weight was detected, the content of 3 - Methyl - histidine （3 - MH） of gastrocriemius was detected by high performance liquid chromatography （ HPLC）, the expression of MAFbx and MuRF - 1 mRNA of gastroenemius was detected by RT - PCR method. Results Compared with the normal control group, the gastrocnemius weight of the model control group decreased significantly （ P 〈 O. 05 ） , the content of 3 - MH within muscular tissue increased significantly （ P 〈 O. 05 ） , the expression of UPP related gene MAFbx and MuRF - 1 mRNA increased significantly （ P 〈 0.05 ） ; Compared with the model control group and medroxyprogester- one acetate group, the gastrocnemius weight of Baoyuan Jiedu Decoction group increased significantly （ P 〈 O. 05 ） , the content of 3 - MH within muscular tissue decreased significantly （ P 〈 O. 05 ） , the expression of MAFbx and MuRF - 1 mRNA decreased sig- nificantly （ P 〈 0.05 ）. Conclusion Baoyuan Jiedu Decoction can improve the skeletal amyotrophia process of cancer cachexia mice, the mechanism of which may be related to lowering the expression of MAFbx,MuRF - 1 , and decreasing the degradation of skeletal muscle contractile protein.