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摘要：
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摘要：目的 探讨不同极化方向巨噬细胞对小鼠活化的肝星状细胞（hepatic stellate cell，HSC）凋亡的
影响及机制。方法 体内构建CCl 4 诱导的肝纤维化小鼠模型和橄榄油对照组小鼠模型，采用流式细胞
术检测不同极化方向巨噬细胞在两组小鼠肝脏中的比例。体外诱导骨髓来源的巨噬细胞极化（M0、
M1、M2巨噬细胞），分别收集上清与活化的LX-2细胞共培养。采用CCK-8法、Caspase-3/7活性检
测、流式细胞术和Western Blot检测LX-2细胞的凋亡。结果 CCl 4 组小鼠肝脏巨噬细胞比例显著高于对
照组（t = 10.86，P ＜ 0.0001），其中M1、M2巨噬细胞的比例均显著高于对照组（t值分别为4.62、
5.28，P值分别为0.0036、0.0007）。与M0和M2巨噬细胞共培养组相比，M1巨噬细胞上清可显著抑制
LX-2细胞的增殖、诱导LX-2细胞的凋亡、增加Caspase-3/7酶活性并上调凋亡蛋白Bax的表达（P均＜
0.05）。此外，M1巨噬细胞肿瘤坏死因子相关凋亡诱导配体（TNF-related apoptosis-inducing ligand，
TRAIL）的表达水平显著高于M0和M2巨噬细胞（t值分别为17.15、17.20，P均＜ 0.0001）。TRAIL重
组蛋白可显著抑制活化的LX-2细胞增殖、促进其凋亡、增强Caspase-3/7酶活性并诱导Bax表达上调。
结论 M1巨噬细胞通过表达TRAIL促进小鼠活化的HSC凋亡。
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Abstract: Objective To investigate the effects and its mechanism of different polarization macrophages on the
apoptosis of activated hepatic stellate cell (HSC) in mice. Methods Mouse models of CCl 4 induced liver fibrosis
and olive oil control were constructed in vivo. The proportion of macrophages with different polarization directions
in liver of mice in two groups were measured by flow cytometry. In vitro, bone marrow derived macrophages
polarization (M0, M1 and M2 macrophage) was induced, and supernatant was collected to co-cultured with activated
LX-2 cells. The apoptosis of LX-2 cells was detected by CCK-8, enzyme activity of caspase-3/7, flow cytometry
and Western Blot. Results The content of hepatic macrophages of mice in CCl 4 group was significantly higher than
that in control group (t = 10.86, P ＜ 0.0001), and the contents of M1 and M2 macrophages were also significantly
higher than those in control group (t = 4.62, 5.28; P = 0.0036, 0.0007). Compared with the co-culture group of M0
and M2 macrophage, M1 macrophage supernatant significantly inhibited the proliferation of LX-2 cells, induced the
apoptosis of LX-2 cells, increased the enzyme activity of Caspase-3/7 and up-regulated the expression of apoptosis
protein Bax (P ＜ 0.05). In addition, the expression levels of TNF-related apoptosis-inducing ligand (TRAIL) of M1
macrophage were significantly higher than those of M0 and M2 macrophage (t = 17.15, 17.20; P ＜ 0.0001). TRAIL
recombinant protein can significantly inhibit the proliferation of activated LX-2 cells, promote their apoptosis,
enhance the activity of Caspase-3/7 enzyme and induce the up-regulation of Bax expression. Conclusion M1
macrophage mediate the apoptosis of activated hepatic stellate cells by expressing TRAIL.
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