Digestive diseases and sciences · 2017
The Protective Effects of Helix B Surface Peptide on Experimental Acute Liver Injury Induced by Carbon Tetrachloride.
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Wu Shengdi, Yang Cheng, Xu Nuo, Wang Lingyan, Liu Yun, Wang Jiyao, Shen Xizhong
Аннотация
BACKGROUND: To investigate the protective effects of helix B surface peptide (HBSP) on acute liver injury induced by carbon tetrachloride (CCl4).
METHODS: HBSP (8 nmol/kg) was intraperitoneally injected into C57 BL/6 mice 2 h after CCl4 administration. Serum and liver tissue samples were collected 24 h after injury. Liver function and histological injuries were evaluated. Inflammatory cell infiltration and cytokines were examined and hepatocytes apoptosis was measured. The human liver cell line LO2 and murine primary hepatocytes were stimulated by CCl4 with and without HBSP treatment and glutathione peroxidase activity, cell survival, and apoptosis were evaluated. In addition, we examined the PI3K/Akt/mTORC1 pathway to elucidate the mechanism underlying HBSP-mediated protection in acute liver injury.
RESULTS: HBSP significantly decreased serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and pro-inflammatory cytokines in liver tissues after CCl4 injection compared with those in the control group. Immunohistochemical staining indicated that the number of CD3-, CD8-, and CD68-positive cells and the expression of cleaved caspase-3 were significantly decreased by HBSP treatment. Additionally, HBSP reduced apoptosis in vivo. In an in vitro study, the glutathione peroxidase activity and survival rate increased, while the total apoptotic rate was reduced in the HBSP-treated group compared with that in the control group after CCl4 treatment. HBSP activated the PI3K/Akt/mTORC1 pathway, which was confirmed by the PI3K inhibitor LY294002 both in vivo and in vitro. Furthermore, HBSP increased the survival of mice with acute liver injury, and this effect was abolished by LY294002.
CONCLUSIONS: HBSP is a potential therapeutic agent against acute liver injury induced by CCl4.
METHODS: HBSP (8 nmol/kg) was intraperitoneally injected into C57 BL/6 mice 2 h after CCl4 administration. Serum and liver tissue samples were collected 24 h after injury. Liver function and histological injuries were evaluated. Inflammatory cell infiltration and cytokines were examined and hepatocytes apoptosis was measured. The human liver cell line LO2 and murine primary hepatocytes were stimulated by CCl4 with and without HBSP treatment and glutathione peroxidase activity, cell survival, and apoptosis were evaluated. In addition, we examined the PI3K/Akt/mTORC1 pathway to elucidate the mechanism underlying HBSP-mediated protection in acute liver injury.
RESULTS: HBSP significantly decreased serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and pro-inflammatory cytokines in liver tissues after CCl4 injection compared with those in the control group. Immunohistochemical staining indicated that the number of CD3-, CD8-, and CD68-positive cells and the expression of cleaved caspase-3 were significantly decreased by HBSP treatment. Additionally, HBSP reduced apoptosis in vivo. In an in vitro study, the glutathione peroxidase activity and survival rate increased, while the total apoptotic rate was reduced in the HBSP-treated group compared with that in the control group after CCl4 treatment. HBSP activated the PI3K/Akt/mTORC1 pathway, which was confirmed by the PI3K inhibitor LY294002 both in vivo and in vitro. Furthermore, HBSP increased the survival of mice with acute liver injury, and this effect was abolished by LY294002.
CONCLUSIONS: HBSP is a potential therapeutic agent against acute liver injury induced by CCl4.
Предметные рубрики MeSH
Alanine TransaminaseAnimalsAntigens, CDAntigens, Differentiation, MyelomonocyticApoptosisAspartate AminotransferasesCD3 ComplexCD8 AntigensCarbon TetrachlorideCell LineCell SurvivalChemical and Drug Induced Liver InjuryChromonesCytokinesEnzyme InhibitorsErythropoietinGene ExpressionGlutathione PeroxidaseHepatocytesHumansL-Lactate DehydrogenaseMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLMorpholinesMultiprotein ComplexesOxidative StressPeptide FragmentsPhosphatidylinositol 3-KinaseProto-Oncogene Proteins c-aktSignal TransductionTOR Serine-Threonine KinasesCD68 Molecule