Purpose: Berberine (BBR) is an effective component of Huanglian and has shown to attenuate atherosclerosis (AS); however, the detailed mechanism of BBR-mediated protective actions against AS remains elusive. This study was undertaken to examine the effects of BBR on aortic atherosclerotic plaque stability and the expression of autophagy-related proteins in AS rats with damp-heat syndrome or yang deficiency.
Methods: Thirty SD rats were randomly divided into (1) control (CON); (2) damp-heat syndrome atherosclerosis (AS + DH); (3) yang deficiency syndrome atherosclerosis (AS + YX); (4) damp-heat syndrome atherosclerosis + BBR (AS + DH + BBR); (5) yang deficiency syndrome, atherosclerosis + BBR (AS + YX + BBR); and (6) damp-heat syndrome, atherosclerosis + BBR + 3-methyladenine (AS + DH + BBR + 3-MA) (n = 5/group) groups. Pathological morphology, macrophage plaque infiltration, inflammation, and LC3-II and P62 expression were assessed.
Results: Compared with the CON group, the AS + DH and AS + YX groups had an increased plaque area in the aortic tissue with substantial foam cell and macrophage infiltration, and increased levels of IL-1β and TNF-α (P < 0.01). After four weeks of BBR intervention, the plaque area in the AS + DH + BBR group was reduced with decreased foam cells and macrophage infiltration, and decreased levels of TNF-α and IL-1β, whereas LC3-II protein expression was increased and P62 protein expression was decreased in the AS + DH + BBR group when compared to AS + DH group. In addition, the AS + DH + BBR + 3-MA group exhibited a significantly enlarged plaque, substantial foam cell and macrophage infiltration, increased levels of IL-1β and TNF-α, and decreased LC3-II and P62 (P < 0.01) expression when compared to the AS + DH + BBR group.
Conclusion: Our results indicated that the BBR could inhibit arterial plaque formation and alleviate the inflammatory response in the aortic tissues in the AS rats with damp-heat syndrome possibly via promoting autophagy. The molecular mechanisms of BBR-mediated protective effects in this animal model still require further investigation.

Keywords: berberine, autophagy, LC3-II, P62, arterial plaque, damp-heat syndrome


中文翻译：

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小檗碱通过调节自噬减轻湿热证大鼠动脉斑块的形成。

目的：小檗碱（BBR）是黄连的有效成分，已显示可减轻动脉粥样硬化（AS）；然而，BBR 介导的抗 AS 保护作用的详细机制仍然难以捉摸。本研究旨在探讨BBR对湿热证或阳虚型AS大鼠主动脉粥样硬化斑块稳定性及自噬相关蛋白表达的影响。
方法：将30只SD大鼠随机分为（1）对照组（CON）；(2)湿热证动脉粥样硬化(AS+DH)；(3)阳虚证动脉粥样硬化(AS+YX)；(4)湿热证动脉粥样硬化+BBR(AS+DH+BBR)；（5）阳虚证、动脉粥样硬化+BBR（AS+YX+BBR）；(6)湿热证、动脉粥样硬化+BBR+3-甲基腺嘌呤(AS+DH+BBR+3-MA)(n=5/组)组。评估病理形态、巨噬细胞斑块浸润、炎症以及 LC3-II 和 P62 表达。
结果：与CON组相比，AS+DH、AS+YX组主动脉组织斑块面积增加，有大量泡沫细胞和巨噬细胞浸润，IL-1β和TNF-α水平升高（P < 0.01）。BBR干预4周后，AS+DH+BBR组斑块面积减少，泡沫细胞和巨噬细胞浸润减少，TNF-α和IL-1β水平降低，而LC3-II蛋白表达增加，P62与 AS + DH 组相比，AS + DH + BBR 组的蛋白表达降低。此外，AS+DH+BBR+3-MA组斑块明显增大，大量泡沫细胞和巨噬细胞浸润，IL-1β和TNF-α水平升高，LC3-II和P62降低（P < 0.01）与 AS + DH + BBR 组相比的表达。
结论：我们的研究结果表明，BBR可能通过促进自噬来抑制湿热证AS大鼠动脉斑块形成并减轻主动脉组织的炎症反应。该动物模型中 BBR 介导的保护作用的分子机制仍需要进一步研究。

关键词：小檗碱，自噬，LC3-II，P62，动脉斑块，湿热证