[Intervention of nutritional status and hypoxia endurance by a nutritional supplement in young adults living at high altitude].

AIM: To investigate the effects of a nutritional supplement on nutritional status and hypoxia endurance in young adults living at high altitude. METHODS: Forty healthy male young adults were recruited and randomly assigned to control and intervention groups. The nutrition survey was carried out using weighing method. The intervention group was given a nutritional supplement specifically designed for use at high altitude, while the control group was treated with a supplement made of stir-fried flour. After 20 days of supplementation, they marched from the altitude of 3700 m to 5100 m. The changes in HR, SaO2, serum concentrations of VA and VB2 and some minerals were measured. RESULTS: The results of nutrition survey showed that the ratio of three macronutrients was not adequate and the intakes of calcium, VA and VB2 were below Chinese RNI. The serum concentrations of calcium, magnesium and VA were below normal references. The serum VB2 concentration was at the low level o f normal reference. The nutritional supplement could increase the serum concentrations of calcium, magnesium, VA and VB2, indicating an improved nutritional status. The changes in HR and SaO2 were diminished in intervention group compared with control group. CONCLUSION: The nutritional supplement can improve nutritional status and increase the hypoxia endurance in young adults living at high altitude.

[Effects of hypoxia on the secretions of proinflammatory cytokines TNF-alpha and IL-6 in macrophages and its mechanism].

AIM: To investigate the effects of hypoxia on the secretions of proinflammatory cytokines TNF-alpha and IL-6 and to inquire into the mechanism. METHODS: Separated mice abdominal macrophages which were identified with non-specific esterase dye method, and created the hypoxic cultured model. The levels of TNF-alpha and IL-6 in the medium were determined by ELISA method. The mRNA expressions of TNF-alpha and IL-6 were measured by RT-PCR method. NF-kappaB activation was assayed by Western blot method. Finaly, we added cortone (5 microg/ml) to the medium, then observed the secretion levels of TNF-alpha and IL-6 during hypoxia. RESULTS: The secretions of TNF-alpha and IL-6 from Mphi exposed to hypoxia for 12 h were increased significantly compared with control (P < 0.01). The expressions of TNF-alpha mRNA and IL-6 mRNA were enhanced obviously contrasted with control (P < 0.01). NF-kappaB activation in Mphi nuclei was raised at 2 h during hypoxia and persisted to 5 h. We added cortone to the medium and found no significant change in secretion of TNF-alpha and IL-6 during hypoxia. CONCLUSION: Hypoxia could activate NF-kappaB and make it shift to nucleus which promoted the transcriptions and expressions of TNF-alpha and IL-6.

[Nuclear factor kappa B signal transduction in macrophages during hypoxia: reactive oxygen species generation].

The effects of hypoxia on the level of reactive oxygen species (ROS), IkappaBalpha tyrosine phosphorylation, transcription of P65 mRNA and NF-kappaB activation in isolated rat peritoneal macrophages were investigated by DCFH-DA fluorescence spectrophotometry, Western blotting and RT-PCR. The results obtained are as follows. (1) During hypoxia, the levels of intracellular ROS began to increase at 1 h, then reached a peak at 2 h, and began to decrease after 3 h. IkappaBalpha tyrosine phosphorylation began to rise after 2 h hypoxia and was the highest after 3 h hypoxia. After 4 h hypoxia it decreased gradually. NF-kappaB activation began to increase after 3 h hypoxia, and reached a peak after 4 h hypoxia. (2) When antioxidant NAC (500 mmol/L) was added into the medium, the level of IkappaBalpha phosphorylation showed no significant changes during hypoxia. After adding protein tyrosine kinase inhibitor genistein (200 micromol/L), NF-kappaB activation induced by hypoxia was blocked significantly. (3) The expression of p65 mRNA was also elevated markedly during hypoxia. These results suggest that hypoxia may lead to IkappaBalpha phosphorylation and NF-kappaB activation through intracellular ROS, and that the regulation of NF-kappaB activity may involve IkappaBalpha phosphorylation and the expressions of each subunit gene of NF-kappaB.

Vascular endothelial growth factor gene expression regulated by protein kinase C pathway in endothelial cells during hypoxia.

Objective. To investigate the relationship between Vascular endothelial growth factor (VEGF) gene expression and protein kinase C (PKC) activity. Method. 1) Rat's primary pulmonary artery endothelial cells (PAEC) were cultured under hypoxia condition (1% O2). Changes of PKC activity and VEGF mRNA in PAEC were detected at 0 (control), 1, 3, 6, and 12 h in the hypoxic condition of culture. 2) After addition of PKC inhibitor (staurosporine) in culture medium and culturing PAEC in hypoxic condition immediately, PKC activity and VEGF mRNA in PAEC were measured at the same time. VEGF protein in culture medium under the two conditions above were also detected. Result. PKC activity in PAEC were obviously elevated at 1 h during hypoxia as compared with the control (P<0.05); VEGF mRNA expression in PAEC and VEGF protein level in culture medium were increased significantly (P<0.01) at 3 h and 6 h during hypoxia respectively as compared with the control (P<0.01); After addition of PKC inhibitor in culture medium and culturing cells in hypoxia condition immediately, PKC activity in PAEC decreased significantly as compared with that at 0 h (P<0.01), and there were no significant changes of VEGF mRNA in PAEC and VEGF protein level in culture medium at any time (P>0.05). Conclusion. The results demonstrate that hypoxia stimulates pulmonary arterial vascular endothelial cells to secrete VEGF, and PKC may be one of the factors that up-regulate VEGF gene expression during hypoxia.