Published online Nov 21, 2015. doi: 10.3748/wjg.v21.i43.12370
Peer-review started: May 5, 2015
First decision: June 3, 2015
Revised: June 18, 2015
Accepted: September 14, 2015
Article in press: September 15, 2015
Published online: November 21, 2015
AIM: To investigate the protective effect of magnesium isoglycyrrhizinate (MgIG) on excessive hepatectomy animal model and its possible mechanism.
METHODS: We used the standard 90% hepatectomy model in Sprague-Dawley rats developed using the modified Emond’s method, in which the left, middle, right upper, and right lower lobes of the liver were removed. Rats with 90% liver resection were divided into three groups, and were injected intraperitoneally with 3 mL saline (control group), 30 mg/kg (low-dose group) and 60 mg/kg (high-dose group) of MgIG, respectively. Animals were sacrificed at various time points and blood was drawn from the vena cava. Biochemical tests were performed with an automatic biochemical analyzer for the following items: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl endopeptidase, total bilirubin (TBil), direct bilirubin (DBil), total protein, albumin, blood glucose (Glu), hyper-sensitivity C-reactive protein, prothrombin time (PT), and thrombin time (TT). Postoperative survival time was observed hourly until death. Hepatocyte regeneration was analyzed by immunohistochemistry. Serum inflammatory cytokines (IL-1, IL-6, IL-10, and iNOS) was analyzed by ELISA. STAT3 protein and mRNA were analyzed by Western blot and quantitative reverse-transcription PCR, respectively.
RESULTS: The high-dose group demonstrated a significantly prolonged survival time, compared with both the control and the low-dose groups (22.0 ± 4.7 h vs 8.9 ± 2.0 vs 10.3 ± 3.3 h, P = 0.018). There were significant differences among the groups in ALT, Glu and PT levels starting from 6 h after surgery. The ALT levels were significantly lower in the MgIG treated groups than in the control group. Both Glu and PT levels were significantly higher in the MgIG treated groups than in the control group. At 12 h, ALT, AST, TBil, DBil and TT levels showed significant differences between the MgIG treated groups and the control group. No significant differences in hepatocyte regeneration were found. Compared to the control group, the high-dose group showed a significantly increase in serum inflammatory cytokines IL-1 and IL-10, and a decrease in IL-6. Both STAT3 protein and mRNA levels were significantly lower in the MgIG treated groups than in the control group at 6 h, 12 h, and 18 h after surgery.
CONCLUSION: High-dose MgIG can extend survival time in rats after excessive hepatectomy. This hepatoprotective effect is mediated by inhibiting the inflammatory response through inhibition of the STAT3 pathway.
Core tip: Magnesium isoglycyrrhizinate (MgIG), a hepatocyte protective agent, has been shown to have the effects of anti-inflammation, liver cell membrane protection, and liver function improvement. We designed this study, by using the standard 90% hepatectomy model in rats, to clarify the liver protecting function of MgIG and its mechanism. We have researched postoperative survival time, hepatocyte regeneration, liver function, serum inflammatory cytokines, STAT3 protein and mRNA expression. The protective effect of MgIG in standard 90% hepatectomy is limited, which can prolong the survival time. This hepatoprotective effect was not mediated by increasing hepatocyte regeneration but rather by inhibiting the inflammatory response through inhibition of the STAT3 pathway.