Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
Eur Rev Med Pharmacol Sci. 2019 Jun;23(11):4996-5003. doi: 10.26355/eurrev_201906_18091.
This study aims to investigate the role of Chi3l1 in Acetaminophen (APAP)-induced liver injury.
In vivo model of liver injury was established in mice administrated with APAP (250 mg/kg) or equivalent phosphate-buffered saline (PBS). Mouse liver tissues were collected at 1 h, 3 h, 6 h, 12 h, and 24 h after treatment, respectively. ALT levels and apoptosis were evaluated. Additionally, we established APAP-induced acute liver injury model in wild-type (WT) mice and Chi3l1-deficient (Chi3l1-/-) mice. Pathological changes of liver tissue were observed by hematoxylin and eosin (HE) staining. Mononuclear cells (MNCs) were isolated from mouse liver, and the amounts of infiltrating macrophages and neutrophils were then counted by flow cytometry. Serum levels of cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Bone marrow-derived macrophages (BMDMs) were extracted from each mouse.
After APAP stimulation, Chi3l1-/- mice showed more severe liver injury than that of WT mice, which was manifested as higher ALT levels and more necrotic or apoptotic cells. Compared with WT mice, Chi3l1-/- mice expressed higher levels of inflammatory cytokines (MCP-1 and IL-6), macrophage-associated molecules (CD68 and CD86), as well as the amounts of infiltrating macrophages and neutrophils. In addition, higher expressions of inflammatory cytokines were found in BMDMs extracted from WT mice treated with those BMDM lysates derived from Chi3l1-/- mice than those of non-treated cells. APAP-treated Chi3l1-/- mice exhibited more severe liver injury than that of WT mice.
Our study confirmed that Chi3l1 protects the liver function from APAP-induced injury by inhibiting the secretion of inflammatory factors and macrophage infiltration.
本研究旨在探讨 Chi3l1 在对乙酰氨基酚（APAP）诱导的肝损伤中的作用。
采用给予 APAP（250mg/kg）或等量磷酸盐缓冲液（PBS）的方法建立小鼠体内肝损伤模型。分别于处理后 1h、3h、6h、12h 和 24h 采集小鼠肝组织，评估 ALT 水平和细胞凋亡情况。此外，我们还在野生型（WT）小鼠和 Chi3l1 缺失型（Chi3l1-/-）小鼠中建立了 APAP 诱导的急性肝损伤模型。通过苏木精和伊红（HE）染色观察肝组织的病理变化。采用流式细胞术计数浸润巨噬细胞和中性粒细胞的数量。通过酶联免疫吸附试验（ELISA）检测血清细胞因子水平。从每只小鼠中提取骨髓来源的巨噬细胞（BMDMs）。
APAP 刺激后，Chi3l1-/- 小鼠的肝损伤比 WT 小鼠更严重，表现为更高的 ALT 水平和更多的坏死或凋亡细胞。与 WT 小鼠相比，Chi3l1-/- 小鼠表达更高水平的炎症细胞因子（MCP-1 和 IL-6）、巨噬细胞相关分子（CD68 和 CD86）以及浸润巨噬细胞和中性粒细胞的数量。此外，与未经处理的细胞相比，从 WT 小鼠中提取的 BMDMs 用来自 Chi3l1-/- 小鼠的 BMDM 裂解物处理后，发现炎症细胞因子的表达更高。APAP 处理的 Chi3l1-/- 小鼠的肝损伤比 WT 小鼠更严重。
本研究证实 Chi3l1 通过抑制炎症因子的分泌和巨噬细胞浸润来保护肝功能免受 APAP 诱导的损伤。
