目的 探讨梓醇对尘肺模型大鼠运动能力及骨骼肌功能的改善作用。方法 通过气管注射石英粉尘建立大鼠慢性尘肺模型，造模3个月后，取造模大鼠30只随机分为3组：模型组、梓醇100mg·kg^-1组、梓醇50mg·kg^-1组，每组10只，另取10只正常大鼠作为对照组。大鼠ig给药，每天1次，每周给药6d，连续给药8周。观察大鼠一般状况及体质量变化；采用小动物跑台检测大鼠的1次力竭运动时间；采用抓力测定仪进行大鼠骨骼肌力量检测；解剖大鼠取同一位置肺叶，HE染色用于观察肺组织基本结构及炎症反应等状态，Masson染色用于观察肺组织胶原沉积和纤维化情况；取双侧后肢的腓肠肌和比目鱼肌，称质量，计算质量指数（肌肉质量/体质量）；试剂盒法检测腓肠肌组织线粒体膜电位（△φ_m）和腺嘌呤核苷三磷酸（ATP）水平；试剂盒法检测腓肠肌组织超氧化物歧化酶（SOD）活性、丙二醛（MDA）水平及琥珀酸脱氢酶（SDH）活性；实时荧光定量PCR（qRT-PCR）法检测过线粒体生物发生相关基因——氧化物酶体增殖物激活受体γ辅激活因子1α（Pgc-1α）、核呼吸因子1（Nrf1）、线粒体转录因子A（Tfam）的mRNA表达水平。结果 与模型组比较，梓醇100、50mg·kg^-1对尘肺大鼠肺部炎症和纤维未见显著改善；梓醇100、50mg·kg^-1均能显著延长尘肺大鼠跑动力竭时间（P＜0.05、0.01）；梓醇可显著增加尘肺大鼠的肌肉抓力，其中100mg·kg^-1组差异显著（P＜0.05）；梓醇100mg·kg^-1组尘肺大鼠的腓肠肌和比目鱼肌质量指数显著增加（P＜0.05、0.01），50mg·kg^-1组的比目鱼肌质量指数显著增加（P＜0.05）；梓醇可明显升高尘肺大鼠腓肠肌ATP水平和△φ_m，其中100mg·kg^-1组差异显著（P＜0.05）；梓醇100mg·kg^-1显著增加腓肠肌SDH和SOD活力、同时降低MDA水平（P＜0.05、0.01），梓醇50mg·kg^-1显著增加腓肠肌SDH活力、同时降低MDA水平（P＜0.05、0.01）；梓醇100、50mg·kg^-1显著上调腓肠肌中线粒体生物发生相关基因表达（P＜0.05、0.01）。结论 梓醇可以调节尘肺模型大鼠骨骼肌线粒体功能，减轻肌肉萎缩并增强运动能力，此作用可能通过PGC-1α/NRF1、TFAM途径促进线粒体生物发生而介导。

Objective To investigate the effect of catalpol on the exercise ability and skeletal muscle function in pneumoconiosis rats.Methods The rat model of chronic pneumoconiosis was established by intratracheal injection of quartz dust. Three months after the model was established, thirty model rats were randomly divided into three groups: model group, catalpol 100 mg·kg^-1 group and catalpol 50 mg·kg^-1 group with 10 rats in each group, and 10 normal rats were selected as control group. The rats were ig given the drug, once a day, for six days a week for eight weeks. The general condition and body mass of rats were observed. The time of one exhaustive exercise of rats was measured by small animal running table. The muscle strength of rats was measured by grip force analyzer. HE staining was used to observe the basic structure and inflammatory response of lung tissue, and Masson staining was used to observe the collagen deposition and fibrosis of lung tissue. The gastrocnemius and soleus muscles of the bilateral hind limbs were taken and weighed, and the mass index (muscle mass/body mass) was calculated. Mitochondrial membrane potential (△φ_m) and adenine riboside triphosphate (ATP) levels in gastrocnemius were determined by kit method. The activity of superoxide dismutase (SOD), malondialdehyde (MDA) and succinate dehydrogenase (SDH) in gastrocnemius were detected by kit method. Real-time quantitative fluorescence PCR (qRT-PCR) was used to detect the mRNA expression levels of oxisome proliferator-activated receptor γ -coactivator 1α (Pgc-1α), nuclear respiratory factor 1 (Nrf1) and mitochondrial transcription factor A (Tfam).Results Compared with model group, catalpol 100 and 50 mg·kg^-1 did not significantly improve pulmonary inflammation and fiber in rats with pneumoconiosis. Compared with model group, catalpol of 100 and 50 mg·kg^-1 could significantly prolong the running exhaustion time of rats with pneumoconiosis (P <0.05, 0.01). Catalpol significantly increased the muscle gripping power of rats with pneumoconiosis, and the difference was significant in 100 mg·kg^-1 group compared with model group (P <0.05). The gastrocnemius muscle mass index and soleus muscle mass index of pneumoconiosis rats in catalpol 100 mg·kg^-1 group were significantly increased (P <0.05, 0.01), and soleus muscle mass index in 50 mg ·kg^-1 group was significantly increased compared with model group (P <0.05). Catalpol significantly increased ATP level and △φm in gastrocnemius of pneumoconiosis rats, and the difference was significant in 100 mg·kg^-1 group (P <0.05). Catalpol of 100 mg·kg^-1 significantly increased the activities of SDH and SOD in gastrocnemius and decreased the level of MDA (P <0.05, 0.01), and catalpol of 50 mg·kg^-1 significantly increased the activities of SDH and decreased the level of MDA in gastrocnemius (P <0.05, 0.01). Catalpol of 100 and 50 mg·kg^-1 significantly up-regulated the expression of mitochondrial biogenesis related genes in gastrocnemius (P <0.05, 0.01).Conclusion Catalpol can regulate the mitochondrial function of skeletal muscle in pneumoconiosis model rats, alleviate muscle atrophy and enhance exercise ability, which may be through PGC-1 α-Nrf1/TFAM pathways promoting mitochondrial biogenesis.

R965

南京市卫生科技发展项目资助(YKK21188);青海省高端创新人才千人计划项目(2018年)