Monoclonal antibody OX26-modified ginsenoside Rg1 nano drug delivery system for promoting angiogenesis and neurogenesis after cerebral infarction / 医学研究生学报

ABSTRACT

Objective Blood-brain barrier(BBB)may stop over 95%of the drugs delivered from entering the brain.This study aimed to establish a BBB model in vitro,detect the ability of the nano drug delivery system to penetrate the BBB,and observe its effect on angiogenesis and neuron cell proliferation after cerebral infarction. Methods A BBB model was established in vitro and the penetrability of PHRO through the BBB was detected by transwell assay.PBS,Rg1,and PHRO were placed in the upper chamber,and the content of Rg1 in the lower chamber was measured by HPLC.The effect of PHRO on angiogenesis was assessed with the in vitro tube formation model and the expression levels of the angiogenesis -related genes VEGFA and Dll4 determined by real time fluorescence quantitative PCR.Brain endothelial cells were incubated with 10 μL PBS(the control group),10 μmol/L Rg1(the Rg1 group),and PHRO(containing 10 μmol/L Rg1,the PHRO group)for 24 hours,and the SH5Y cells incubated the same way in the three groups for 72 hours.The effects of PHRO on the proliferation and apoptosis of the SH5Y cells were detected by MTT assay and flow cytometry respectively.The SH5Y cells were treated with 10 μL PBS(the PBS con-trol group),1 mmol/L Na2S2O4(the hypoxia-induction group),1 mmol/L Na2S2O4plus 10 μmol/L Rg1(the hypoxia-induction +Rg1 group),and 1 mmol/LNa2S2O4plus PHRO(including10 μmol/L Rg1,the hypoxia-induction +PHRO group), respectively. Results The content of Rg1 was 3.18%in the Rg1 group,28.8%in the PHRO group,and 0 in the control group.The angiogenesis of endothelial cells was markedly increased in the Rg 1 group as compared with the control(P<0.05), and even more significantly in the PHRO than in the Rg1 group(P<0.05).In comparison with the control group,the expressions of VEGFA and Dll 4 and the prolif-eration of the SH5Y cells were remarkably elevated in the Rg 1 group(P<0.05)and even more significantly in the PHRO than in the Rg1 group(P<0.05).The apoptosis rate of neurons was the lowest in PBS control(1.2%)and the highest in the hypoxia-induction group(21.6%),decreased to 13.14%and 8.25%in the hypoxia-induction +Rg1 and hypoxia-induction +PHRO group,respectively. Conclusion PHRO nanomedicine could penetrate the blood-brain barrier in vitro, promote angiogenesis and neuronal proliferation, reduce the apoptosis of neurons under hypoxia,and up-regulate the expressions of angiogenesis-related genes.