- 作者: Yong Li; Dingguo Zhang; Yuqing Zhang; Guoping He; Fumin Zhang
- 作者服務機構: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, R.R. China
- 中文摘要: --
- 英文摘要:
Objectives We postulated that combining high-dose simvastatin with bone marrow
derived-mesenchymal stem cells (MSCs) delivery may give better prognosis in a
mouse hindlimb ischemia model.
Methods Mouse hindlimb ischemia model was established by ligating the right
femoral artery. Animals were grouped (n=10) to receive local injection of saline
without cells (control and simvastatin groups) or with 5 × 106 MSCs (MSCs
group).Animals received either simvastatin (20mg/kg/d, simvastatin and combination
groups) or saline(control and MSCs group) gavages for continual 21 days. The blood
flow was assessed by laser Doppler imaging at day 0,10and 21 after surgery,
respectively. Ischemic muscle was harvested for immunohistological assessments and
for VEGF protein detection using western blot assay at 21 days post-surgery. In vitro,
MSCs viability was measured by MTT and flow cytometry following culture in
serum-free medium for 24 h with or without simvastatin. Release of VEGF by MSCs
incubated with different doses of simvastatin was assayed using ELISA.
Results Combined treatment with simvastatin and MSCs induced a significant
improvement in blood reperfusion, a notable increase in capillary density, a highest
level of VEGF protein and a significant decrease in muscle cell apoptosis compared
with other groups. In vitro, simvastatin inhibited MSCs apoptosis and increased
VEGF release by MSCs.
Conclusions Combination therapy with high-dose simvastatin and bone
marrow-derived MSCs would augment functional neovascularization in a mouse
model of hindlimb ischemia. - 中文關鍵字: --
- 英文關鍵字: --