目的:基于“久坐伤肉”探讨四君子汤预防失用性肌萎缩作用,并围绕肌肉干细胞(muscle stem cell,MuSC)/肌核域(myonuclear domain,MND)途径研究其作用机制。方法:40只雄性大鼠按随机分为正常组、悬尾组(模型组)、悬尾+跑轮组(运动组)、悬尾+蒸馏水组(蒸馏水组)和悬尾+四君子汤预防组(中药组)；采用大小鼠抓力仪检测四肢抓力；电子秤计量大鼠股四头肌(quadriceps femoris, QF)湿重；ELISA法检测肌动蛋白和肌球蛋白含量；Image Pro 6.0软件计算肌纤维的横断面积(cross section area,CSA)和肌核数,进而计算MND；免疫荧光法检测配对盒基因(paired box gene 7,Pax7)和成肌分化抗原(myogenic differentiation antigen,MyoD)表达。结果:与正常组相比,模型组及蒸馏水组的四肢抓力、QF湿重、肌球蛋白含量、CSA及MND均下降,Pax7阳性细胞数量升高；与模型组及蒸馏水组相比,运动组和中药组的四肢抓力、QF湿重、肌球蛋白含量、CSA及肌核数均上升,Pax7及MyoD阳性细胞数均增加,但运动组的Pax7阳性细胞数明显多于中药组。结论:四君子汤能够预防失用性肌萎缩,其机制与激活MuSC/MND途径有关。

【】Objective: to study the action of Sijunzi decoction preventing disuse atrophy and its mechanism on the pathway of muscle stem cell (MuSC)/myonuclear domain (MND) based on the theory of sedentary behavior damaging muscle. Methods: 40 male rats were randomly divided into the normal group, tail hanging group (model group), tail hanging + exercise group (exercise group), tail hanging + distilled water group (DW group), tail hanging + sijunzi decoction ( Chinese medicine (CM) group); grip strength of limbs was measured by Grip Strength Meter for rats and mice; the wet weight of quadriceps femoris (QF) was measured by electronic scales; concentrations of actin and myosin were detected by ELISA; the cross section area (CSA) and myonuclear numbers were detected with Image Pro 6.0, and then MNDs were calculated; the expressions of pair box gene 7 (Pax7) and myogenic differentiation antigen (MyoD) were detected by immunofluorescence. Results: compared with those in the normal group, grip strength, QF wet weight, the myosin concentration, the CSA and MND in the model and DW groups were all decreased, the numbers of Pax7 were increased? significantly; compared with those in the model and distilled water groups, grip strength, QF wet weight, the myosin level, CSA and myonuclear numbers in the exercise group and CM groups were increased, and the numbers of Pax7 and MyoD positive cells were increased,markedly, however the number of Pax7 positive cells in the exercise group was more than that in the CM group significantly. Conclusion: sijunzi decoction can prevent disuse atrophy and its possible mechanism is related? to the activation the MuSC/MND pathway.

国家自然科学基金青年项目(81803986):四君子汤干预脾气虚骨骼肌线粒体未折叠蛋白反应-自 噬-细胞凋亡机制的研究；负责人：刘文俊，作者参与。 辽宁省教育厅面上项目（LJKMZ20221322 ）：基于线粒体质控研究四君子汤预防久坐性肌萎缩的作用机制；负责人：单德红，作者参与。 辽宁中医药大学中西医结合学院“岐济”人才支撑计划（英才）项目（2023QJ03001）：基于肌肉干细胞的增殖分化研究四君子汤对久坐模型大鼠股四头肌肌核域的影响；负责人：马丹。