目的 采用大脑中动脉栓塞（middle cerebral artery occlusion，MCAO）大鼠模型，探究菊花Chrysanthemum morifolium提取物对缺血性脑卒中后肌肉萎缩的改善作用。方法 雄性SD大鼠随机分为假手术组、模型组、二甲双胍（0.2 g/kg）组和菊花提取物高、低剂量（1.08、0.54 g/kg）组，每组7只。建立MCAO大鼠模型，连续给药7 d。通过激光散斑系统评估MCAO模型稳定性；采用Zea-Longa评分评估大鼠的神经功能损伤；采用小动物跑步机评估运动能力；使用小动物超声系统检测肌肉厚度。末次行为学检测后，取比目鱼肌，测定长度和质量，采用苏木素-伊红（hematoxylin-eosin，HE）染色检测肌肉细胞横截面积；采用ELISA法检测血清和比目鱼肌中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-1β（interleukin-1β，IL-1β）、IL-6水平；采用免疫组化法检测比目鱼肌中肌肉细胞特异性泛素蛋白连接酶-1（muscle ring-finger protein-1，MuRF1）和肌肉萎缩F盒蛋白（muscle atrophy F box protein，MAFbx）的表达；采用Western blotting检测比目鱼肌中MuRF1、MAFbx、TNF-α和IL-6的蛋白表达。结果 与模型组比较，菊花提取物可以改善MCAO模型大鼠的神经功能损伤和运动能力（P＜0.01、0.001），增加肌肉厚度、比目鱼肌长度和质量（P＜0.05、0.01、0.001），改善术后肌肉细胞横截面减少（P＜0.05），降低血清和比目鱼肌中TNF-α、IL-1β和IL-6水平（P＜0.05、0.01、0.001），下调比目鱼肌中MuRF1、MAFbx、TNF-α和IL-6的表达（P＜0.05、0.01、0.001）。结论 菊花提取物能够通过抑制血清和肌肉中炎症因子水平，下调肌肉萎缩因子MuRF1和MAFbx的表达，减少肌肉蛋白质分解，从而提高卒中后大鼠的运动能力并改善肌肉萎缩。

Objective To investigate the improvement effect of Chrysanthemum morifolium extract on muscle atrophy after ischemic stroke using a rat model of middle cerebral artery occlusion (MCAO). Methods Male SD rats were randomly divided into sham group, model group, metformin (0.2 g/kg) group, C. morifolium extract high- and low-dose (1.08, 0.54 g/kg) groups, with seven rats in each group. MCAO rat model was established and drugs were administered continuously for 7 d. The stability of MCAO model was evaluated through laser speckle system; The Zea-Longa score was used to evaluate the neurological damage in rats; A small animal treadmill was used to evaluate exercise ability; A small animal ultrasound system was used to detect muscle thickness. After the last behavioral test, the soleus muscle was taken and its length and weight were measured. Hematoxylin-eosin (HE) staining was used to detect the cross-sectional area of muscle cells; ELISA was used to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in serum and soleus muscle; Immunohistochemistry was used to detect the expressions of muscle ring-finger protein-1 (MuRF1) and muscle atrophy F box protein (MAFbx) in soleus muscle; Western blotting was used to detect the protein expressions of MuRF1, MAFbx, TNF-α, and IL-6 in soleus muscle. Results Compared with model group, C. morifolium extract could improve the neurological damage and motor ability of MCAO model rats (P < 0.01, 0.001), increase muscle thickness, soleus muscle length and weight (P < 0.05, 0.01, 0.001), improve the reduction of muscle cell cross-section after surgery (P < 0.05), reduce the levels of TNF-α, IL-1β and IL-6 in serum and soleus muscle (P < 0.05, 0.01, 0.001), and down-regulate the expressions of MuRF1, MAFbx, TNF-α and IL-6 in soleus muscle (P < 0.05, 0.01, 0.001). Conclusion C. morifolium extract can improve the motor ability and muscle atrophy of post-stroke rats by inhibiting the levels of inflammatory factors in serum and muscle, down-regulating the expressions of muscle atrophy factors MuRF1 and MAFbx to reduce muscle protein breakdown.

R285.5

国家自然科学基金青年科学基金项目(82104732);成都中医药大学杏林学者项目(BSH2020022);天府青城计划专项-天府名师(500005006)