Role of HO-1/BMMSCs in improving hepatic microcirculation after reduced-size transplantation in rats / 中华器官移植杂志

ABSTRACT

Objective:To explore the role of heme oxygenase-1 (HO-1) modified bone marrow mesenchymal stem cells (BMMSCs) in improving hepatic microcirculation after reduced-size liver transplantation (RLT) in rats.Methods:BMMSCs were isolated and cultured in vitro by adherence method. Then HO-1/adenovirus (Adv) was transfected for constructing HO-1/BMMSCs. The "dual-sleeve" method was employed for establishing an acute rejection model after 50% RLT. Immediately post-operation, 1 ml normal saline (NS) and BMMSCs or HO-1/BMMSCs single cell suspension were injected. The changes of surviving rats were observed by parameters at Day 3/7/14 post-operation. Five rats were observed at each timepoint. The serum level of mitochondrial aspartate aminotransferase (mAST) was detected; Na+ -K+ -ATPase in transplanted liver was measured by chemical colorimetry; mitochondrial ultrastructural changes were observed under a transmission electron microscope. Portal vein pressure was detected by Power Lab at Day 7 post-operation; the expressions of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and von Willebrand factor (vWF) in liver tissues were detected by Western blot. Liver histopathological changes were observed by hematoxylin & eosin stain. The expression of vWF was detected by immunohistochemistry and serum level of hyaluronic acid (HA) detected by enzyme-linked immunosorbent assay (ELISA).Results:HO-1/BMMSCs could significantly lessen the pathological injury and rejection of 50% reduced-size transplanted liver, improve mitochondrial damage and energy metabolism, promote the expression of eNOS, suppress the expression of iNOS, reduce portal pressure, up-regulate the expression of hepatic sinus vWF and HA degradation, protect hepatic sinusoidal endothelial cells (SECs) and ultimately improve hepatic microcirculation. And the differences were statistically significant as compared with NS/BMMSCs group ( P<0.05). Conclusions:HO-1/BMMSCs may play an important role in protecting rat liver by improving hepatic microcirculation during RLT.