Chunhua Ma, Hongyan Long
Central Laboratory, Nanjing Municipal Hospital of T.C.M, The Third Affiliated Hospital of Nanjing University of T.C.M, Nanjing 210001, China.
Central Laboratory, Nanjing Municipal Hospital of T.C.M, The Third Affiliated Hospital of Nanjing University of T.C.M, Nanjing 210001, China.
Int J Biol Macromol. 2017 Jun;99:648-654. doi: 10.1016/j.ijbiomac.2017.03.024. Epub 2017 Mar 6.
The present study was designed to investigate the beneficial effects of pilose antler peptide (PAP) against carbon tetrachloride (CCl) hepatotoxicity in mice, and explore the underlying mechanisms. In our results, animals were treated with either CCl and/or PAP for six consecutive weeks. The levels of inflammatory cytokines in serum and liver, hepatotoxicity markers in serum and histopathological evaluation were determined. PAP (50, 100mg/kg) significantly inhibited the CCl-incuded overproduction of inflammatory cytokines including tumor necrosis factor α (TNF-α), cytokines interleukin-1β (IL-1β), and interleukin-6 (IL-6) in serum and liver. Animals treated with PAP exhibited lower levels of alanine transaminase (ALT) and aspartate transaminase (AST), PAP administration alleviated CCl induced hepatic fibrosis as manifested in histopathological records. In fact, PAP prevented the activation of TLR/NF-κB pathway, by inhibiting the expression of TLR2, TLR4 MyD88, p-NF-κBp65 and p-IκBα. In addition, PAP also significantly reversed CCl4-induced alteration of TGF-β and p-samd-3 in liver tissue. In conclusion, PAP restored CCl4-induced hepatotoxicity via TLR/NF-κB and TGF-β/samd-3 pathways.
本研究旨在探讨鹿茸多肽(PAP)对小鼠四氯化碳(CCl)肝毒性的有益作用,并探索其潜在机制。在我们的研究结果中,动物连续六周接受CCl和/或PAP治疗。测定血清和肝脏中炎症细胞因子水平、血清中肝毒性标志物以及进行组织病理学评估。PAP(50、100mg/kg)显著抑制了CCl诱导的血清和肝脏中包括肿瘤坏死因子α(TNF-α)、细胞因子白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)在内的炎症细胞因子的过量产生。接受PAP治疗的动物丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平较低,PAP给药减轻了CCl诱导的肝纤维化,这在组织病理学记录中有所体现。事实上,PAP通过抑制TLR2、TLR4、MyD88、p-NF-κBp65和p-IκBα的表达,阻止了TLR/NF-κB通路的激活。此外,PAP还显著逆转了CCl4诱导的肝组织中TGF-β和p-samd-3的改变。总之,PAP通过TLR/NF-κB和TGF-β/samd-3通路恢复了CCl4诱导的肝毒性。