Therapeutic Effects of Baicalin Combined with Bone Marrow Stromal Cells on Hepatic Ischemia/Reperfusion Injury in Rats

Abstract

Background and Purpose: Hepatic ischemia-reperfusion (I/R) injury has been considered a primary hindrance in liver operation. This study explored the efficiency of baicalin combined with bone marrow stromal cells (BMSCs) in treating rats’ liver I/R injury. Methods: BMSCs hepatic differentiation was evaluated by determining the expression of hepatic markers, urea synthesis, and low-density lipoprotein (LDL) uptake after the identification of BMSCs. Hepatic injury was evaluated via Hematoxylin and Eosin (H&E) staining, LDH activity, and Reactive Oxygen Species (ROS) levels. Apoptosis in liver tissue was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and flow cytometry. The inflammatory cytokines levels were determined using enzyme-linked immunosorbent assay (ELISA). Oxidative stress damage was assessed using Superoxide Dismutase (SOD) activity. The target molecules expression was detected via Polymerase Chain Reaction (real-time PCR) and western blotting. Key Results: Results showed that baicalin facilitated hepatic differentiation of BMSCs, as evidenced by enhancing expression of albumin (ALB), Cytokeratin-18 (CK-18), and alpha fetoprotein (AFP), urea production, and LDL uptake. As compared with BMSCs monotherapy, co-treatment with baicalin exhibited higher efficiency in attenuating liver injury. Moreover, combination with baicalin strengthened the inhibitory effect of BMSCs on apoptosis via reducing the expression of B-cell lymphoma-2 (Bcl-2) Associated X Protein (Bax) and cleaved caspase-3 but elevating the expression of Bcl-2. Additionally, oxidative stress and inflammatory response were restrained by combination with baicalin and BMSCs treatments. Finally, the promotion of Heme Oxygenase 1 (HO-1) expression and inactivation of the nuclear factor kappa-B (NF-κB) pathway were involved in the molecular mechanisms of this combined therapy. Conclusions and Implications: In summary, combined therapy of baicalin and BMSCs showed higher efficiency in mitigating hepatic I/R injury than monotherapy, and this therapeutic action may depend on activating HO-1 and inhibiting the activation of NF-κB.