P38与ERK在慢性低氧高二氧化碳小鼠骨骼肌凋亡中的作用

The Role of P38 & ERK in Apoptosis of Skeletal Muscle of Chronic Hypoxia-hypercapnia Mice

探讨P38与ERK信号通路在慢性低氧高二氧化碳小鼠骨骼肌凋亡中的作用。该研究将造模组小鼠置于低氧高二氧化碳舱内，氧浓度9％～11％，二氧化碳浓度5％～6％，每天8小时，每周6天，共4周。称量小鼠体重；观察骨骼肌细胞形态及线粒体结构；检测骨骼肌线粒体和胞浆内CytC和AIF含量：检测B别mRNA、Bcl-xlmRNA、p-P38蛋白与P—ERK蛋白的表达。结果显示，造模组小鼠体重减轻：骨骼肌纤维断裂，脂肪沉积；线粒体膜部分破坏，嵴排列紊乱；线粒体内CytC、AIF含量降低，胞浆内CytC、AIF含量升高；BadmRNA表达增多，而Bcl-xl，mRNA表达减少；p—P38蛋白与p-ERK蛋白表达增多。因此，慢性低氧高二氧化碳导致小鼠骨骼肌凋亡，可能与激活P38与ERK信号通路，促进Bad活化，抑制Bcl—x1活化，从而促进CytC、AIF释放到胞浆，最终导致凋亡有关。

To investigate the role of P38 and ERK in apoptosis of skeletal muscle of chronic hypoxia-hypercapnia mice. The hypoxia hypercapnia group mice were placed in a sealed chamber, where 02 concentration maintained at 9%-11%, and CO2 concentration maintained at 5%-6%, for 8 hours a day, 6 days a week, 4 weeks. The weight of mice was weighted. The cell morphology and the mitochondrial structure of skeletal muscle were ob-served. The content of Cytochrome C and apoptosis-inducing factor in the mitochondria and in the cytoplasm was determined. The expression of Bad mRNA, Bcl-xl mRNA, p-P38 protein and p-ERK protein was detected. The re- suits showed that the HH group mice had lost weight. There was fibers fracture and fat deposition in the HH group mice. The mitochondrial membrane was partially destroyed, and the cristae was disorganized. The content of Cyt C and AIF in the mitochondria was reduced, while the content of Cyt C and AIF in the cytoplasm was increased. The expression of Bad mRNA was increased, while the expresson of Bcl-xl mRNA was decreased. The expression of p-P38 protein and p-ERK protein was increased. Thus, apoptosis of skeletal muscle of mice was induced by chronic hypoxic hypercapnia. P38 and ERK signaling pathway might be in the process of apoptosis, by activating the Bad, inhibiting the Bcl-xl and promoting Cvt C and AIF releasing into the cvtonlasm.