Objective To investigate the dynamic expression from gene and protein levels of hypoxia inducible factor-1α(HIF-1α) during the development of hypoxic pulmonary hypertension (HPH) in neonatal rats.Methods A neonatal rat model of HPH was established,normal neonatal rats were enrolled as the control group.At the 3th 、7th、10th and 14th days,we measured the mRVSP through catheterization of right ventricule,collected hearts to figure out the right ventricular hypertrophy index(RVHI),evaluated vascular remodeling by the percentage of medial thickness to outer diameter of the small pulmonary arteries (MT％) and the percentage of medial cross section on area to the total cross section area of the pulmonary small arteries (MA％),observed the expression of HIF-1α by immunochemistry,and measured the expression of HIF-1α in mRNA and protein by RT-PCR and Western blot respectively.Results The mRVSP increased at the 3th day,and sustained until the 14th day (P ＜ 0.01).RVHI MT％ and MA％ increased at the 7th day,and sustained until the 14th day (P ＜0.01).HIF-1α mainly expressed in endothelium and smooth muscle cells in the CHPH group and the HIF-1αmRNA increased significantly on the 3th and 7th days (P ＜ 0.05),and the HIF-1α protein increased significantly on the 7th、10th and 14th days in the CHPH group compared with the control group(P ＜ 0.01).Conclusion The mRVSP increased at the early stage after hypoxic exposure in neonatal rats,followed by vascular remodeling and right ventricular hypertrophy.Both mRNA and protein levels of HIF-1α sustained higher than control group during the vascular remodeling stage,indicating that HIF-1α might be a important factor contributing to the vascular remodeling.

OBJECTIVE ToexplorethepossiblemechanismoractiontargetsofT-2toxinembryo toxicity by observing the effect of T-2 toxin on mitochondrial function of differentiated murine e mbryonic stemcells(mESCs).METHODS Duringdifferentiationat24,72and120h,ESCswereexposedto T-2 toxin 0.5 μg·L-1 .Meanwhile,mESCs were pre-treated with antioxidant Trolox (200 μmol·L-1 )for 30 min and exposed to T-2 toxin (0.5 μg·L-1 )for 72 h.The mitochondrial ultrasture of differentiated mESCs was observed under a transi mission electrical microscope (TEM).The differentiated ESC mito-chondrial function,including respiratory control ratio (RCR),ATP synthase activity and mitochondrial membranepotential(MMP),wasmeasuredat144hafterdifferentiation.RESULTS Significant decrease of the mitochondrial number,deformation of mitochondrial structure,and lack of complete mito-chodrial crest were observed through TEM in the groups of T-2 toxin exposed for 72 and 1 20 h,respec-tively.Compared with the normal control group,RCR declined by 49.5% and 55.1%,ATP synthase activity decreased by 84.9% and 89.3%,and MMP decreased by 23.2% and 35.2% in T-2 toxin 0.5 μg·L-1 exposure 72 and 1 20 h group,respectively.However,the inhibition of mitochondrial function by T-2 toxin in differentiated mESCs recovered significantly in the presence of the antioxidant Trolox. CONCLUSION T-2toxininducesoxidativestressandinhibitsmESCsmitochondrialfunctionindifferenti-ated mESCs,and ROS-induced mitochondrial malfunction plays an i mportant role in T-2 toxin e mbryonic toxicity mechanis m.