Effects of recombinant human granulocyte-colony stimulating factor therapy on rat pulmonary hypertension and its influence on endothelial progenitor cells / 中华围产医学杂志

ABSTRACT

Objective To investigate the effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) therapy on pulmonary hypertension,and its influence on number and functions of circulating endothelial progenitor cells (EPCs) in rats.Methods Eight week old Sprague-Dawlay rats were randomized into model group,treatment group and control group (8 rats in each group).The rats in model group and treatment group were treated with single subcutaneous injection of 1％ monocrotaline (50 mg/kg) to induce pulmonary hypertension models,while the control group was treated with phosphate buffered saline.Five days later,the rats in treatment group were administrated with 50 μg/(kg· d) rhG-CSF for 3 days.On day 21,peripheral blood was collected from caudal vein in all groups,and the percentage of EPCs in 100 000 mononuclear cells was evaluated by flow cytometry.Right ventricular systolic pressure was assessed,and the pathological changes of lung tissue and pneumoangiogram were observed by HE staining.Meanwhile,peripheral mononuclear cells collected from caudal vein were separated and cultured in vitro for EPCs.The cell ffunctions as proliferation,adhesion and migration ability were assessed.ANOVA and LSD test were applied as statistical analysis methods.Results (1) The right ventricular systolic pressure of rats in model group was higher than that in the controls [(48.13 ± 2.85) mm Hg vs (27.88 ± 3.04) mm Hg,t=2.016,P＜0.01],the lesion of endothelial cells in pulmonary arteriolar was evident,and the vessel wall was thickened.The pulmonary artery pressure of rats in the treatment group [(30.38 ± 2.83) mm Hg] was lower than that in the model group and close to the level of control group (t=0.376,P＞0.05) with mild pulmonary pathological changes.(2) The percentage off peripheral blood EPCs in mononuclear cells in the model group was decreased as compared to the control group [(0.016±0.007) ％ vs (0.031±0.011) ％,t=2.617,P＜0.01].After administration ofrhG-CSF,the EPCs in treatment group [(0.042±0.013) ％] was increased evidently as compared to the model group (t=4.325,P＜0.01) and the control group (t =1.942,P＜0.05).(3) The proliferation,adhesive and migrated cells of EPCs in model group were 0.49 ± 0.04,(6.93 ± 1.47) cells/HPF and (7.22±1.53) cells/HPF,lower than those in control group [0.68±0.07,(11.05±1.73) cells/HPF and (12.58±2.15) cells/HPF] and treatment group [0.63±0.06,(12.35±1.82) cells/HPF and (12.97±2.84) cells/HPF],the differences were statistically significant(all P＜0.05).Conclusions rhG-CSF may be effective in treating pulmonary hypertension through up-regulating the number and function of circulating EPCs in rat model of pulmonary hypertension.