*Purpose: The hepatic damages are inevitable under liver surgery. Therefore, post-hepatectomy liver failure remains one of the most dangerous and life-threatening complications of hepatectomy. The outcome of liver surgery can be improved by increasing liver regeneration. Substance P has a healing effect on damaged tissues. In this study, we investigated the effect of substance P on regeneration after liver resection(LR) in rat.

*Methods: SD rats aged 8 weeks were used. Animals were divided into three groups: Sham (n = 5); Control (n = 5, injected with saline after LR; SP (n = 5, injected with SP after LR). Liver resection was performed with 70% hepatectomy. The liver regeneration effect of SP was assessed by PCNA, CD133, phosphated mTOR, Akt, ERK, and p38.

*Results: In the Sham, Saline and SP groups, the aspartate transaminase were 83.75 ± 7.14, 3417.23± 2148.34 and 687.62± 219.48, and alanine transferase were 52.25 ± 6.29, 2002.8 ± 1335.69, and 605.52 ± 214.27 on POD1. Total bilirubin was 0.11 ± 0.01, 0.84 ± 0.75, and 0.46 ± 0.27 on POD1. These showed significant lower results in the SP than in the control POD1 (POD1, injected only on the operative day(OD) and examined on POD1) (fig.1). As a result of PCNA (fig.2), it was represented a strongly expressed pattern in SP compared to control group on POD1 & 2 (POD2; OD and POD1, total 2 injections and examined on POD2). There were significant differences between groups (p < 0.05). Phosphated ERK was significantly increased in SP group compared than saline group (fig.3).

*Conclusions: In Rat hepatectomy models, substance P had liver regeneration effect on early stage. It is considered to be effective in liver regeneration within 24 hours of Substance P injection. SP may have the potential to improve the recovery and prognosis after liver surgery.

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