ABSTRACT

Background

Papain possesses a potential anti-atherosclerosis (AS) effect. This study aimed to explore the inhibitory effects of papain on the monocyte-platelet aggregates (MPAs)-mediated production of foam cells in vitro and AS in vivo.

Research design and methods

THP-1 cells were treated by platelet, papain, nuclear factor-κB (NF-κB) inhibitor or activator. An AS rat model was treated with papain. The THP-1 cells, macrophages, and foam cells were detected, and CD36, CD11b and CCR2 (macrophages) and CD14 and CD41 (MPAs) were measured. The levels of inflammatory factors, lipoprotein, and MAPK and PI3K/Akt -NF-κB pathways proteins were determined. Finally, injury of the thoracic aorta of AS rats was observed.

Results

Papain reduced macrophage production, lipid accumulation, and foam cell formation in vitro and downregulated the expression of monocyte chemoattractant protein 1 (MCP-1), prostaglandin E2 (PGE2), and cyclooxygenase 2 (COX2), and that of p38, JNK, Akt, and p65. Moreover, NF-κB activator could reversed the inhibitory effects of papain. Similarly, papain alleviated aortic smooth muscle hyperplasia, lipid droplet accumulation, and collagen diffusion and inhibited the expression of inflammatory factors and p38, JNK, Akt, and p65 in vivo.

Conclusions

Papain inhibited MPA-induced foam cell formation by inactivating the MAPK and PI3K/Akt-NF-κB pathways, thereby exerting an anti-AS effect.

中文翻译：

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木瓜蛋白酶通过调节 MAPK 和 PI3K/Akt-NF-κB 通路抑制 MPA 介导的泡沫细胞形成，发挥抗动脉粥样硬化作用

摘要

背景

木瓜蛋白酶具有潜在的抗动脉粥样硬化 (AS) 作用。本研究旨在探讨木瓜蛋白酶对单核细胞-血小板聚集体 (MPA) 介导的体外和体内AS泡沫细胞产生的抑制作用。

研究设计和方法

THP-1 细胞经血小板、木瓜蛋白酶、核因子-κB (NF-κB) 抑制剂或激活剂处理。用木瓜蛋白酶处理 AS 大鼠模型。检测了 THP-1 细胞、巨噬细胞和泡沫细胞，并测量了 CD36、CD11b 和 CCR2（巨噬细胞）以及 CD14 和 CD41（MPA）。测定了炎症因子、脂蛋白、MAPK 和 PI3K/Akt -NF-κB 通路蛋白的水平。最后观察AS大鼠胸主动脉的损伤情况。

结果

木瓜蛋白酶在体外减少巨噬细胞的产生、脂质积累和泡沫细胞的形成，并下调单核细胞趋化蛋白 1 (MCP-1)、前列腺素 E2 (PGE2) 和环氧合酶 2 (COX2) 以及 p38、JNK、Akt 的表达和 p65。此外，NF-κB 激活剂可以逆转木瓜蛋白酶的抑制作用。同样，木瓜蛋白酶可减轻主动脉平滑肌增生、脂滴积聚和胶原扩散，并抑制体内炎症因子和 p38、JNK、Akt 和 p65 的表达。

结论

木瓜蛋白酶通过使 MAPK 和 PI3K/Akt-NF-κB 通路失活来抑制 MPA 诱导的泡沫细胞形成，从而发挥抗 AS 作用。