跑台训练联合中药松弛膏外敷对废用性肌萎缩大鼠骨骼肌细胞凋亡及IGF-1/PI3K/Akt信号通路的影响  

The effect of supplementing treadmill training with relaxation cream in cases of disuse muscle atrophy

作　　者：阿斯古丽·图尔荪 束娇娇 努尔比亚·克其克 夏热帕·阿不都拉 杨芮琦 哈丽米热·阿卜杜吉力力 帕丽达·买买提[1,3] Asiguli Tuersun;Shu Jiaojiao;Nurbia Keqike;Xiarepa Abudula;Yang Ruiqi;Halimire Abdujilili;Palida Maimnaiti(School of Nursing,Xinjiang Medical University,Urumqi 830017,China;Rehabilitation Medicine Department of The First Afiliated Hospital of Xinjiang Medical University,Urumqi 830054,China;Health Care Research Center for Xinjiang Regional Population,Urumqi 830017,China)

机构地区：[1]新疆医科大学护理学院,乌鲁木齐830017 [2]新疆医科大学第一附属医院康复医学科,乌鲁木齐830054 [3]新疆区域人群疾病与健康照护研究中心,乌鲁木齐830017

出　　处：《中华物理医学与康复杂志》2024年第8期692-698,共7页Chinese Journal of Physical Medicine and Rehabilitation

基　　金：国家自然科学基金项目(82060417, 81660380)。

摘　　要：目的观察跑台训练联合中药松弛膏外敷对废用性肌萎缩(DMA)大鼠骨骼肌细胞凋亡及胰岛素样生长因子-1(IGF-1)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路的影响。方法选取8周龄雄性Wistar大鼠46只, 取8只大鼠纳入健康对照组(健康组), 余38只大鼠则制成左后肢废用性肌萎缩模型。于造模3周后采用随机数字表法将制模成功的32只大鼠分为模型对照组(模型组)、跑台训练组(跑台组)、中药松弛膏组(中药组)及跑台训练联合中药松弛膏组(联合组), 每组8只大鼠。跑台组大鼠给予跑台训练, 中药组大鼠则于患肢局部涂抹中药松弛膏, 联合组大鼠给予跑台训练及中药松弛膏患肢局部涂抹。于6周干预结束后采用原位末端标记法(TUNEL)检测各组大鼠骨骼肌细胞凋亡情况;采用蛋白免疫印迹法(Western blot)检测各组大鼠骨骼肌中IGF-1、磷酸化PI3K(p-PI3K)、磷酸化Akt(p-Akt)、B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)等因子表达水平。结果通过TUNEL染色发现, 跑台组、中药组、联合组骨骼肌凋亡细胞数量均较模型组明显减少(P<0.05);联合组凋亡细胞数量亦显著低于跑台组及中药组水平(P<0.05)。通过Western blot检测发现, 模型组Bcl-2蛋白表达较健康组显著降低, Bax蛋白表达则显著增高(P<0.01);与模型组比较, 中药组及联合组Bcl-2蛋白表达均显著增高(P<0.01), Bax蛋白表达则显著降低(P<0.01);另外联合组Bcl-2蛋白表达均明显高于中药组及跑台组水平, Bax蛋白表达则显著低于中药组及跑台组水平(P<0.05)。与模型组比较, 中药组、联合组IGF-1、p-PI3K及p-Akt蛋白表达均显著升高(P<0.01);联合组IGF-1、p-PI3K、p-Akt蛋白表达亦较跑台组及中药组显著增高(P<0.01)。结论跑台训练联合中药松弛膏外敷能抑制DMA大鼠骨骼肌细胞凋亡, 其作用机制可能与激活IGF-1/PI3K/Akt信号通路, 继而上调抑凋亡蛋白Bcl-2含量, 下调促凋亡ObjectiveTo observe any effect supplementing treadmill training with external application of relaxation cream on skeletal muscle cell apoptosis and IGF-1/PI3K/Akt signaling.MethodsEight Wistar rats formed a healthy control group(the healthy group)and muscle atrophy was induced in the left hind limbs of another 32.Those 32 rats were randomly divided into a model control group(model group),a treadmill training group(treadmill group),a relaxation cream group(TCM group),and a group which received both treadmill training and the relaxation cream(combined group).After 6 weeks of the intervention,terminal deoxynucleotidyl transferase nick-end labeling(TUNEL)was used to detect any apoptosis of skeletal muscle cells.Western blotting was employed to detect the protein expression levels of insulin-like growth factor 1(IGF-1),phosphorylated PI3K(p-PI3K),phosphorylated Akt(p-Akt),B-cell lymphomato-2(Bcl-2)and Bcl-2 associated X protein(Bax)in the skeletal muscles.ResultsThe number of apoptotic cells in the skeletal muscles of the treadmill,TCM and combined groups was significantly less,on average,then in the model group.The difference in the combined group was significantly greater than in the other two groups.The expression of Bcl-2 protein in the model group was significantly lower than in the healthy group,while that of Bax protein had increased significantly.Compared with the model group,a significant increase in Bcl-2 protein expression and a significant decrease in Bax protein expression were observed in both the TCM and combined groups.Compared with the model group,the expression of IGF-1,p-PI3K and p-Akt proteins had increased significantly in both the TCM and combined groups,with significantly greater increases in the combined group,on average.ConclusionCombining treadmill training with relaxation cream can inhibit the apoptosis of skeletal muscle cells,at least in DMA rats.The mechanism may be related to activation of the IGF-1/PI3K/Akt signaling pathway,up-regulation of Bcl-2 and down-regulation of Bax.

关 键 词：废用性肌萎缩 IGF-1/PI3K/Akt信号通路 细胞凋亡 B细胞淋巴瘤-2(Bcl-2) Bcl-2相关X蛋白(Bax) 

分 类 号：R685[医药卫生—骨科学]