| Objective: To investigate the effects of different doses of 2-methox yest radiol on the expression of estrogen receptors(ER)in the hypoxic pulmonary rat models,and try to explore the mechanism of 2ME on t he hypoxic pulmonary hypertension(HPH)and pulmonary vascular re modeling.Methods:Fifty healthy female Sprague-Dawdley rats were divided randomly i nto 5 groups,namely sham operation+oxygen group,ovariectomy(OVM)+hypoxia group,OVM+hypoxia+2ME low dose group,OVM+hypoxia+2ME middle dose group,OVM+hypoxia+2ME high dose group.The sha m operation+oxygen group was only opened the abdominal cavity of the rats and found ovaries,which was not treated and returned directly,pl aced into normal air environment.The OVX rats were removed the bila teral ovaries and received different concentrations of 2ME(72?mol·kg-1·d-1240?mol·kg-1·d-1 720?mol·kg-1·d-1)and placed into hypoxic environment fo r 8 weeks continuously,to establish a model of hypoxic pulmonary hyp ertension(HPH).To observe the general condition of rats,application of right heart catheterization after heparin namely polyethylene catheter thro ugh external jugular vein cannulation,superior vena cava,right ventricle into the pulmonary artery,measure pulmonary artery pressure,after that specimens from blood samples,lung,heart,through the formula to calc ulate right ventricular hypertrophy index(RVHI),using HE dyeing obser vated lung small artery remodeling.By ELISA kits to detect the serum level of 2ME.Using immunohistochemical method detected the ER?,E R?,and PCNA about the location and expression in the pulmonay.Results:1 The general condition of ratsUnder prolonged time hypoxic condition,the rats decreased activity,reduced water and food intake,loss of weight,dark coat hairs and easy to fall off,breathing rate to speed up,and ultimately lying still most of the time.There was no death during 8 weeks under hypoxic condition.Compared with sham operation+oxygen group(313.67 ± 7.024),OVX+hypoxia group(258.33± 7.572)weight gain were slow.Compared with OVX+hypoxia+2ME high dose group(308.33 ± 6.028),the increase weight of OVX+hypoxia group was slow.2 Changes in pulmonary artery pressure of rats(mPAP)Compared with sham operation+oxygen group(13.23±0.85),the mPAP of the OVX+hypoxia group(30.95 ± 1.53)was significantly increased;compared with the OVX+hypoxia group,the mPAP of different doses of2 ME intervention rats were decreased(OVX+hypoxia+2ME high dose group was 17.44 ± 0.84;OVX+hypoxia+2ME middle dose group was 21.20 ±0.77;OVX+hypoxia+2ME low dose group was 22.46±1.30),and the mPAP of OVX+hypoxia+2ME high dose group reducted the greatest,the low and middle dose of 2ME compared had no statistical difference.3 Morphological changes in pulmonary small vessels and the right ventricle in ratsUnder light microscopy,the pulmonary artery wall cells of sham operation+oxygen group distributed homogeneously continuous,without edema or necrosis;the OVX+hypoxia group pulmonary arteriolar wall thickening,the number of smooth muscle cells were increased,lumen narrowed;2ME intervention group rats the morphology change relatively light,and OVX+hypoxia+2ME high dose group changes lightest.Compared with the sham operation+oxygen group(0.22 ± 0.02),the RVHI of hypoxic condition rats were increased;compared with OVX+hypoxia group(0.31±0.01),the RVHI of 2ME intervention group rats were reduced,but no statistical differences among three doses.4 The change of 2ME content in serum of ratsCompared with the sham operation+oxygen groups(9.42 ± 1.05),the content of 2ME in serum of OVX+hypoxia group(7.88±0.46)was decreased,the content of 2ME in serum of 2ME intervention group was increased,and OVX+hypoxia+2ME high dose group(11.37±0.64)was the most obviously increased.5 ImmunohistochemicalER?,ER?,and PCNA in lung tissue were visible expressioned,positive reaction is tan,located in the nucleus,accidentally found in the cytoplasm.Sham operation+oxygen group sliced visible ER?,ER? staining was positive;the expression of ER? was reduced in OVX+hypoxia group,PCNA staining in deep tan strong positive reaction;2ME intervention group ER? expression increased,PCNA expression decreased.Conclusions:1 2ME can improve the hypoxic pulmonary hypertension and pulmonary vascular remodeling of the rat effectively.2 2ME can regulate the expression of ER? to play the protective role of hypoxic pulmonary hypertension. |
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