The Study On The Experssions Of IGF-1 And IGF-2 In Bone Marrow Mononuclear Cells And Supernatant Of Chronic Mountain Sickness

Objective The chronic mountain sickness (CMS) is a kind of erythrocyte hyper-proliferative disease, the generation of which is directly related with the environmental conditions in the high altitude, such as hypobaric hypoxia, and is regulated by various hematopoietic growth factors (HGF) and apoptotic factors. Insulin-like growth factor (IGF)-1 is an important regulatory factor of hematopoiesis. Researches proved that hypoxia can induce the expression of IGF system which regulates hypoxia-inducible-1. Human hematopoietic progenitors express IGF-1,IGF-2 and IGF receptors, and could secreted IGFs by autocrine/paracrine way. The aim of this study was to explore preliminarily the role of IGF-1 and IGF-2 in the pathogenesis of CMS by evaluating the expressions of IGF-1 and IGF-2 in bone marrow mononuclear cells (BMMNCs) of CMS patients and detecting protein levels of IGF-1 and IGF-2 of bone marrow supernatant.Methods The CMS was diagnosed according to " the diagnostic criteria for CMS of the 6th international plateau medical and low oxygen physiological academic conference ". The bone marrow specimens were collected from 18 patients with CMS (CMS group) and 16 healthy men (control group) . They were all males and ethnic Han. The average ages were 47.05±11.65 years old in CMS group and 50.29±16.24 years old in control group. The BMMNCs were separated from the bone marrow specimens using lymphocytes separation medium. The IGF-1 mRNA and IGF-2 mRNA were measured by semi-quantitative RT-PCR technique, the protein levels of IGF-1 and IGF-2 was measured by solid-phase double antibody sandwich ELISA. The levels of mRNA and protein of IGF-1 and IGF-2 were compared between two groups.Results IGF-1 mRNA and IGF-2 mRNA expressed relatively at a level of 0.639±0.320 and 0.613±0.325 in the CMS group and 0.177±0.12 and 0.216±0.175 in the control group, respectively. They were significantly higher in the CMS group than those in the control group (p<0.01). The protein levels of IGF-1 and IGF-2 were (229.3±93.7)ng/ml and (192.3±46.3)ng/ml in the CMS group and (110.1±16.0) ng/ml and IGF-2 (85.9±8.2) ng/ml in the control group, respectively. They were also significantly higher in the CMS group than those in the control group(p<0.01). In the CMS group, there were positive correlations between the protein concentration and mRNA for both IGF-1 and IGF-2 (r values were 0.730 and 0.778, respectively, both P<0.01); The hemoglobin concentration was positively correlated with both IGF-1 mRNA expression and IGF-2 mRNA ((r values were 0.590 and 0.585, respectively, P<0.01) and with the protein concentration of IGF-1 and IGF-2 ((r values were 0.609 and 0.672, respectively, P<0.01). SaO₂ was negatively correlated with both IGF-1 mRNA and IGF-2 mRNA (r values were -0.619 and -0.591, respectively, P<0.01) and with both the protein concentration of IGF-1 and IGF-2(r values were -0.591 and -0.573, respectively, P<0.01).Conclusions The expressions of IGF-1 and IGF-2 in BMMNCs increased and were positively correlated with hemoglobin concentration and SaO₂ negatively correlated with SaO₂ in the CMS patients. These resluts indicated that hypoxia probably induce expressions of IGF-1 and IGF-2 in bone marrow cells directly or by the pathway of hypoxia-inducible-1. IGF-1 and IGF-2 could promote excessive proliferation of hematopoietic cells by the autocrine/paracrine way, which may be involed in the pathogenesis mechanism of CMS.