关键词: 急性肝衰竭, Cathelicidin-PY, 凋亡, 抑菌肽, 半胱氨酸天冬氨酸蛋白酶3, 小鼠

Abstract: Objective The aim of this study was to explore the protective effect and possible mechanism of antimicrobial peptide cathelicidin-PY in mice with lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver failure (ALF). Methods 60 C57BL/6 mice were randomly divided into control, model, low-dose cathelicidin-PY (1.0 mg.kg^-1) –intervention and high-dose cathelicidin-PY (3.0 mg.kg^-1) intervention group, with 15 mice in each group. The models of ALF in mice were established by intraperitoneal injection of LPS/D-GalN, and in intervention groups 2 hours before injection of LPS/D-GalN, the mice were injected with cathelicidin-PY via the tail vein. At 5 hours after LPS/D-GalN injection, the blood samples and liver tissues were collected in 5 sacrificed mice in each group, and the survivals within 24 hours of the residual mice was recorded in each group. Serum tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) levels were detected by ELISA, and the apoptosis of liver cells was detected by TUENL staining. The expression of cleaved cysteine proteinase 3 (cleaved caspase-3) in liver tissues was detected by Western blot. Results The 24 h survival rates in low-dose and high-dose cathelicidin-PY intervention groups were 40% (4/10) and 60% (6/10), significantly higher than 10.0% (1/10, P<0.05) in the model; serum TNF-α and IL-1β levels in the model group were (1069.4±178.0) pg/mL and (1354.1±162.9) pg/mL, both significantly higher than [ (140.7 ± 33.6) pg/mL and (436.2 ± 46.8) pg/mL, respectively, P<0.05] in the control, while serum TNF-α and IL-1β levels in the low-dose and high-dose cathelicidin-PY intervention groups decreased significantly compared to in model group (P<0.05); the numbers of apoptotic liver cells and expression of cleaved caspase-3 protein in liver tissues in the model group increased significantly (P<0.05) compared to in the control, while the numbers of apoptotic liver cells decreased, and the expression of cleaved caspase-3 protein became weak significantly compared to in the model in the low-dose and in the high-dose cathelicidin-PY intervention group (P<0.05). Conclusion The antimicrobial peptide, the cathelicidin-PY could reduce mortality in mice with LPS/D-GalN-induced ALF, probably by relieving inflammation response and inhibiting apoptosis of liver cells.

Key words: Acute liver failure, Antimicrobial peptide, Cathelicidin-PY, Apoptosis, Cysteine proteinase 3, Mice