To explore the mechanism of action of catechin (CAT) on mice with a model of high altitude polycythemia through mediating the intestinal hypoxia-inducible factor-2α (HIF2α) iron metabolism pathway.

SPF-grade male Balb/cmice were randomly divided into control group (reared in a normal atmospheric pressure environment: northeastern Qinghai province, China, at an altitude of 2 260 m, 36°73′ north latitude, 101°75′ east longitude, without any treatment), model group (reared in a high-altitude hypoxic environment: a certain place in southwestern Qinghai province, China, at an altitude of 4 208 m, 32°90′ north latitude, 95°25′ east longitude, without any treatment), the experimental group (based on model group, intragastrically administered with 100 mg·kg^-1 CAT once a day from the 29th to the 35th day) and the oe-HIF2α group (based on experimental group, intravenously injected with lentivirus-coated oe-HIF2α plasmids by the tail vein once a day from the 34th to the 35th day). Real-time fluorescence quantitative polymerase chain reaction was used to detect the relative expression level of HIF2α mRNA in intestinal tissues; Western blot assay was used to detect the relative expression levels of HIF2α, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cleaved-cysteine-aspartic acid protease 3 (Cleaved-Caspase3), ferroportin (FPN), transferrin receptor (TFRC) in intestinal tissues, as well as the relative expression levels of GATA binding factor 1 (GATA-1) and erythropoietin receptor (EpoR) in bone marrow red blood cells; automatic hematology analyzer was used to detect the levels of hemoglobin, red blood cell count and hematocrit in peripheral blood; the spectrophotometric method was used to detect the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and content of malondialdehyde (MDA) in intestinal tissues; the immunofluorescence staining assay was used to detect the positive expression of ferritin (Ferritin) in intestinal tissues.

The relative expression levels of HIF2α mRNA in control group, model group and experimental group were 1.00±0.18, 1.61±0.16 and 1.21±0.13, respectively; the hemoglobin levels in control group, model group, experimental group and oe-HIF2α group were (132.91±11.44), (221.37±26.92), (178.65±19.32) and (206.33±21.37) g·L^-1, respectively; the red blood cell count levels were (4.79±0.75), (9.26±1.11), (6.08±1.03) and (7.74±0.96)×10¹²·L^-1, respectively; the hematocrit levels were (44.17±4.06)%, (63.58±6.38)%, (51.79±4.45)% and (58.24±5.07)%, respectively; the relative expression levels of GATA-1 protein were 1.00±0.17, 2.03±0.33, 1.52±0.19 and 1.80±0.23, respectively; the relative expression levels of EpoR were 1.00±0.11, 1.83±0.31, 1.29±0.20 and 1.62±0.24, respectively; the relative fluorescence intensities of Ferritin were 1.00±0.12, 7.86±0.97, 2.97±0.49 and 4.75±0.51, respectively; the relative expression levels of FPN protein were 1.00±0.14, 1.69±0.25, 1.31±0.18 and 1.52±0.19, respectively; the relative expression levels of TFRC protein were 1.00±0.10, 2.18±0.23, 1.67±0.15 and 1.86±0.15, respectively. There were statistically significant differences in the above-mentioned indicators between model group and control group, between experimental group and model group, and between oe-HIF2α group and experimental group (all P<0.05).

CAT can inhibit cell apoptosis, oxidative stress and excessive iron metabolism in the intestines of mice with high altitude polycythemia by mediating the expression of intestinal HIF2α, and play a role in the prevention and treatment of high altitude polycythemia.