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The high altitude/hypoxic environment induced skeletal muscle atrophy is considered to be the interaction of multi-system and multi-organ, but the direct mechanism of hypoxia on muscle cells in this process is not clear. This study intended to investigate the effects of hypoxia exposure on proteins in ubiquitin and autophagy pathways, and explored the possible mechanism of hypoxia induced change of myotube diameter. The expression of myosin, hypoxia inducible factor-1 α (HIF-1α), forkhead box protein O1 (FoxO1), and ubiquitin protease pathway (MuRF1 and Atrogin1) and autophagy lysosomal pathway (p62, Beclin1, LC3) related proteins were detected by Western blot; The integrated optical density (IOD) of Myosin and LC3 was detected by IF. The results showed that the diameters of myotube at 6 h and 12 h were significantly reduced, and the expression of myosin was significantly reduced at 6 h after hypoxia exposure (P<0. 05); the protein levels of HIF-1α and FoxO1 were significantly increased at 6 h (P<0. 05); The expression of MuRF1 in each time points of hypoxia was significantly higher than 0 h (P<0. 05), but no difference of Atrogin1 expression was detected; Compared with 0 h, the expression of p62 was reduced significantly in response to hypoxia. The protein expression of Beclin1 and the IOD of LC3 was increased significantly at 6 h, and the LC3Ⅱ/Ⅰ ratio was significantly higher at 6 h, but significantly lower at 12 h and 24 h (P<0. 05).The results above indicated that the reduction of the myotube diameter of L6 skeletal muscle cells was induced by hypoxia exposure (1% O
RESUMO
BACKGROUND: Changes of red blood cell in peripheral blood and bone marrow erythropoietic system in plateau pikas are of great significance for hypoxic adaptation. OBJECTIVE: To explore the hypoxic adaptation of erythropoietic system in plateau pikas by comparing the morphological changes of peripheral blood and bone marrow between plateau pikas and rats exposed to hypoxia. METHODS: There were 12 healthy wild plateau pikas and 12 clean Sprague-Dawley rats and were randomly divided into experimental and control groups, 6 in each group. The experimental group animals were fed in a simulated 5 000 m altitude hypobaric hypoxia chamber for 28 consecutive days, and the control group animals were fed in the laboratory at 2 260 m altitude. RESULTS AND CONCLUSION: (1) The diameter of the erythrocytes was smaller and red blood cell count was higher in plateau pikas than those in the rats of control group. After 28 days of hypoxia, red blood cell count, hemoglobin and hematocrit were increased in both experimental groups (P < 0.001), but the increased rate of plateau pikas were less than that of the rats. The mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration showed no significant changes in plateau pikas. (2) Results of bone marrow smear showed that the proportion of polychromatic and orthochromatic erythroblasts had no significant changes in plateau pikas after hypoxia, but increased significantly in the rats (P < 0.05). (3) Hematoxylin-eosin staining results of the sternum indicated that the immature erythroblasts islands did not change significantly in plateau pikas, but increased significantly in rats. (4) So the erythroid changes in peripheral blood and bone marrow of plateau pikas before and after hypoxia are significantly lower than those of the Sprague-Dawley rats, and they may be related to the hypoxia adaptation mechanism.
RESUMO
Objective To explore the effect of hypoxic training on the barrier function of intestinal mucous membrane and underlying mechanism in rats.Methods Eighty 5-week-old male Sprague-Dawley rats were randomly divided into a control group,an exercise training group,a hypoxia control group and a hypoxia exercise group,each of 20.The altitude training was conducted through swimming training in artificial hypoxia environment.Two and 6 weeks after the intervention,the tissue structure and ultrastructure of small intestine mucosa were observed.The content of diamine oxidase (DAO)and D-lactate (D-LA),tumor necrosis factor-α (TNF-α)and nuclear factor κB (NF-κB)in plasma and the mRNA level of occludin in ileal tissue were measured.Results (1)Electron microscopy data showed that,after six weeks,compared with the control group,the microvilli of rats in the exercise training group were sparser and arranged irregularly.Furthermore,the gap between epithelial cells became wider.In addition,the number of mitochondria decreased significantly and cristae were vague.For the hypoxia control group,the microvilli shortened significantly and arranged irregularly.Moreover,the gap between cells became wider with partial denatured mitochondria.For the Hypoxia exercise group,the number of mucosal epithelium microvilli in the bowels reduced significantly and the microvilli shortened significantly.Similar to that of the hypoxia control group,the gap between epithelium cells growed wider.However,the cellular structure were fuzzier,and the denature of mitochondria worsened,with the cristae being vague even disappearing partially.(2)Two weeks of exercise training reduced the number of intestinal microvilli significantly (P＜0.01),but increased the plasma level of the DAO and D-LA,as well as the expression level of NF-κB in intestinal tissue significantly (P＜0.05).Hypoxic exposure significantly reduced the mRNA level of oceludin in small intestine (P＜0.01),but significantly increased the plasma level of DAO and D-LA (P＜0.05 vs.control)and the expression of TNF-α and NF-κB in small intestine (P＜0.01).There was no significant interaction between two weeks of exercise training and hypoxia exposure either on the reduction of the number and height of intestinal microvilli,or the transcription level of occluding in small intestine,or the plasma level of DAO and D-LA,or the expression of TNF-α and NF-κB in small intestine (P＞0.05).(3)Both exercise training for six weeks and hypoxia exposure significantly reduced the number and height of microvilli in small intestine (P＜0.01)and the occludin level in small intestine,but significantly increased the plasma level of DAO and DLA (P＜0.01),the expression of TNF-α (P＜0.01,P＜0.05)and NF-κB (P＜0.01).Meanwhile there was significant interaction between six-week exercise training and hypoxia exposure on decreasing the number (P＜0.01)and the height (P＜0.05)of microvilli in small intestine.Conclusion (1)Both intensive training and hypoxia exposure can impair intestinal mucosal barrier function and the extent of damage is correlated with the duration of training and hypoxia exposure.(2)Hypoxic exposure and intensive training may reduce the expression of occludin mRNA through increasing the expression of TNF-α and NF-κB in the small intestine,which in turn increases intestinal permeability and intestinal mucosa inju