以週邊血液血管內皮前驅幹細胞治療慢性腎臟衰竭的大白鼠動物模型
吳彥廷1 陳彥達1 葉漢根2 黃田宏3
高雄長庚紀念醫院泌尿科1，心臟內科2，轉譯中心3
Peripheral blood-derived endothelial progenitor
cell therapy prevented deterioration of
chronic kidney disease in rats
Yen-Ting Wu, M.D.1, Yen-Ta Chen, M.D1. , Hon-Kan Yip2, Tien-Hung Huang3
Kay L.H. Wu, Ph.D.3, Julie Y.H. Chan. Ph.D.3*
Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Division of Urology1, Department of Cardiology2,
Institute for Translational Research in Biomedicine3
Purpose: This study tested the hypothesis that peripheral blood-derived endothelial progenitor cell
(PBDEPC) therapy can impede the deterioration of chronic kidney disease (CKD) induced by 5/6 nephrectomy in rats.
Materials and Methods: Adult-male rats (n = 30) were equally categorized into group 1 (sham control), group 2 (CKD only) and group 3 [CKD + PBDEPC (left intra-arterial (3.3 × 105) and penile vein (6.7 × 105) injections by day 14 after CKD induction].
Results: By day 60, kidney blood flow (KBF) was significantly lower in group 2 than that in groups 1 and 3, and significantly lower in group 3 than that in group 1, whereas the levels of serum creatinine, and kidney injury score and size showed an opposite pattern compared to that of KBF among all groups (all p < 0.001). Protein expressions of apoptotic (caspase 3, PARP), inflammatory (TNF-α, MMP-9), oxidative-stress (oxidized protein, NOX-1), fibrotic (Smad3, TGF-β), and hypoxic/ischemic cell-stress (HIF-1α, p-Akt) biomarkers showed an opposite pattern,
whereas angiogenesis at protein (eNOS, CD31) and cellular (CD31+, CXCR4+) levels showed an identical pattern compared to that of blood flow in all groups (all p < 0.01). Other pro-angiogenic biomarkers (SDF-1α, CXCR4, VEGF) at protein and cellular levels and antioxidants (HO-1+, NQO 1, GR+) at cellular level showed progressive significant increase from groups 1 to 3 (all p < 0.001).
Conclusions: The results support that PBDEPC therapy effectively inhibits
the propagation of CKD and the deterioration of renal function through enhancement of angiogenesis, blood flow, and anti-oxidative capacity as well as suppression of inflammation, oxidative stress, apoptosis, and fibrosis in a rodent model.