Preparation of pitavastatin-loaded poly lactic-co-glycolic acid nanoparticles and their effects on proliferation of endothelial progenitor cells / 中国药科大学学报

@#The objectives of this study were to prepare pitavastatin-loaded poly lactic-co-glycolic acid nanoparticles(PLGA), to characterize their pharmaceutical properties, to conduct in vitro drug-release from the nanoparticles, and to observe the effects on the proliferation of endothelial progenitor cells. Both pitavastatin-loaded PLGA and blank PLGA nanoparticles were prepared using emulsion-solvent diffusion method with PLGA being carrier materials. Morphology of the nanoparticles was observed by scanning electron microscopy(SEM), and particle size was analyzed by laser nanometer particle size analyzer. The drug loading and encapsulation efficiency were assayed using high-performance liquid phase. Impact of blank and pitavastatin-loaded nanoparticles on the viability of endothelial progenitor cells was investigated by CCK8 method. Pitavastatin-loaded PLGA nanoparticles exhibited the structure with spherical shape, smooth surface and average diameter of(230. 1±45)nm. The drug loading capacity and encapsulation efficiency were(10. 00±1. 83)% and(35. 54±5. 40)%, respectively. In vitro sustained-release of pitavastatin from the nanoparticles was found. The blank PLGA nanoparticles had no effect on the viability of the endothelial progenitor cells in different concentrations. Compared with pitavastatin group, pitavastatin-loaded nanoparticles(0. 01 μmol/L, 0. 1 μmol/L)had more effects on the proliferation of endothelial progenitor cells. In conclusion, emulsion-solvent diffusion method is applicable in preparation of pitavastatin-loaded PLGA nanoparticles with good shape and sustained-release of interest. Pitavastatin-loaded nanoparticles could significantly improve proliferation of the endothelial progenitor cells.

Expression of Jagged2/Notch3 signaling molecules in pulmonary hyper-tensive rats induced by monocrotaline / 中国病理生理杂志

AIM:To study the expression of Jagged 2/Notch3 signaling molecules in pulmonary vascular wall of pulmonary hypertensive rats induced by monocrotaline .METHODS: SD rats were randomly divided into normal control group (C group,n=15), solvent control group (S group,n=15) and monocrotaline model groups (M group,n=15).The model of pulmonary hypertension was established by a single subcutaneous injection of monocrotaline (50 mg/kg).The rats in S group were given a single subcutaneous injection of the same dose of solvent .After 4 weeks, the pulmonary vascular remodeling was assessed by HE staining , and the mean pulmonary artery pressure ( mPAP) and right ventricular systolic pressure (RVSP) were determined by right heart catheterization .The expression of Jagged2/Notch3 /Hes5 molecules in the pulmonary vascular wall was detected by immunohistochemical method and real -time PCR.RESULTS:Compared with S group and C group , the percentage of medial wall thickness of smaller arteries in model group increased significantly (P<0.01).The levels of mPAP and RVSP in M group were significantly higher than those in S group and C groups (P<0.01).The results of real-time PCR showed that the expression of Jagged 2, Notch3 and Hes5 was significantly increased in M group compared with S group and C group .The data from immunohistochemical detection indicated that Jagged 2 mainly expressed in the intima of small lung artery , Notch3 and Hes5 mainly expressed in the medial smooth muscle cells .Com-pared with S group and C group , the expression of Jagged 2 and Notch3 was significantly increased in the lung small arteries of M group.CONCLUSION:The activation of Jagged2/Notch3 signaling pathway might play an important role in the for-mation of pulmonary hypertension .

Platelet derived growth factor receptor β over-expression in endothelial progenitor cells promote reendothelialization after vascular injury / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effect of platelet derived growth factor receptor β (PDGFR-β) transfected endothelial progenitor cells (EPCs) on vascular regeneration.</p><p><b>METHODS</b>Spleen-derived mononuclear cells (MNCs) were isolated using density gradient centrifugation and induced with special culture medium. EPCs transfection was performed with Lipofectamine(TM) 2000 reagent according to the instruction manual. Carotid artery injury was induced in splenectomized mice. EPCs were injected by tail vein immediately and at 24 h after endothelial injury of the carotid artery. Evans blue staining was performed to evaluate reendothelialization at 7 days after endothelial injury of the carotid artery.</p><p><b>RESULTS</b>Most adherent cells were LDL and UEA-I double positive. Laser scanning confocal microscopy showed that transfection efficiency was about 50%-60%. The reendothelialized area in the PDGFR-β-EPCs group was significantly larger than that in EGFP-EPCs group.</p><p><b>CONCLUSION</b>Transplantation of PDGFR-β over-expressed EPCs can promote reendothelialization in the early phase after carotid artery injury.</p>

Establishment and evaluation of uremic atherosclerosis models in ApoE~(-/-) mice / 第三军医大学学报

Objective To establish uremic atherosclerosis models in apoE~(-/-) mice and evaluate its feasibility.Methods Totally 70 6-week-old male apoE~(-/-) mice were randomized into 2 groups,uremic group(n=35) and nonuremic control group(n=35).All mice were fed with a Western diet.Uremic group mice underwent partial kidney ablation with electrocoagulation of right renal cortex followed by left total nephrectomy in 2 weeks later and control animals underwent sham operation.Serum levels of urea,total cholesterol and triglycerides were assessed at 0,2,4,6 and 8 weeks after the first surgery.The cross-section surface area of the lesion and the lesion area fraction were assessed.Results At 6 weeks after nephrectomy,the level of serum urea in chronic renal failure(CRF) mice was 188.3% higher than that of control mice,and total cholesterol and triglyceride concentrations were increased by 40.8% and 29.8% than those of nonuremic controls,respectively(P