The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice.
The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice.
复制标题
DOI：
10.18632/oncotarget.11168
复制
发表时间：
2016-09-06
期刊：
影响因子：
--
通讯作者：
Yang SR
中科院分区：
文献类型：
--
作者：
Park JR;Lee H;Kim SI;Yang SR
三肽-铜复合物甘氨酰-I-组氨酰-I-赖氨酸-Cu（II）（GHK-Cu）参与伤口愈合和组织重塑。虽然GHK-Cu具有抗衰老和组织更新的特性，但其在急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）中的作用仍不清楚。因此，我们研究了GHK-Cu在体外脂多糖（LPS）诱导的RAW 264.7巨噬细胞和小鼠体内ALI中的作用。GHK-Cu可通过抑制NF-κB p65和p38 MAPK信号通路，减少活性氧（ROS）的产生，提高超氧化物歧化酶（SOD）活性，降低TNF-α和IL-6的产生。此外，GHK-Cu减轻LPS诱导的肺组织学改变，抑制LPS诱导的小鼠ALI中炎性细胞向肺实质的浸润。综上所述，这些发现表明GHK-Cu通过抑制过度的炎症反应而对LPS诱导的ALI具有保护作用;因此，它可能代表ALI/ARDS的新治疗方法。
The tripeptide-copper complex glycyl-l-histidyl-l-lysine-Cu (II) (GHK-Cu) is involved in wound healing and tissue remodeling. Although GHK-Cu exhibits anti-aging and tissue renewing properties, its roles in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are still unknown. Therefore, we examined the effects of GHK-Cu in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in vitro and ALI in mice in vivo. GHK-Cu treatment reduced reactive oxygen species (ROS) production, increased superoxide dismutase (SOD) activity while decreased TNF-α and IL-6 production through the suppression of NF-κB p65 and p38 MAPK signaling in vitro and in vivo model of ALI. Moreover, GHK-Cu attenuated LPS-induced lung histological alterations, suppressed the infiltration of inflammatory cells into the lung parenchyma in LPS-induced ALI in mice. Taken together, these findings demonstrate that GHK-Cu possesses a protective effect in LPS-induced ALI by inhibiting excessive inflammatory responses; accordingly it may represent a novel therapeutic approach for ALI/ARDS.