Berberine reduces gut-vascular barrier permeability via modulation of ApoM/S1P pathway in a model of polymicrobial sepsis.,Life Sciences

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Berberine reduces gut-vascular barrier permeability via modulation of ApoM/S1P pathway in a model of polymicrobial sepsis.
Life Sciences ( IF 5.2 ) Pub Date : 2020-09-19 , DOI: 10.1016/j.lfs.2020.118460
Yanning Li ₁ , Jun Zhou ₁ , Jiasheng Qiu ₁ , Zudong Huang ₁ , Weiwei Wang ₁ , Ping Wu ₂ , Aiwen Feng ₁

Affiliation

Aims

The hyperpermeability of gut-vascular barrier (GVB) plays a role in gut-derived sepsis. The goal of this study was to evaluate if berberine might improve hepatic apolipoprotein M (ApoM) generation and raise plasma ApoM level to protect the compromised GVB.

Materials and methods

The compromised GVB was induced by sepsis. Hepatic ApoM mRNA and phosphoenolpyruvate carboxykinase (PEPCK) mRNA and plasma ApoM level were assayed by qRT-PCR and ELISA, respectively. The permeability of intestinal capillary in vivo and of rat intestinal microvascular endothelial cells (RIMECs) in vitro was assayed by FITC-dextran. The blood glucose was detected by a glucometer. Plasma insulin, TNF-α and IL-1β were assayed by ELISA. The plasmalemma vesicle-associated protein-1 (PV1), β-catenin and occludin in RIMECs were assayed by Western blot.

Key findings

Sepsis decreased hepatic ApoM mRNA and plasma ApoM level, but raised hepatic PEPCK mRNA and plasma glucose, insulin, TNF-α, and IL-1β levels. The increased vascular endothelial permeability was abrogated by recombinant rat ApoM in vivo or ApoM-bound S1P in vitro. ApoM-bound S1P decreased PV1 but increased occludin and β-catenin expression in LPS-treated RIMECs. Berberine in a dose-dependent manner raised hepatic ApoM mRNA and plasma ApoM level, but decreased septic hyperglycemia, insulin resistance and plasma TNF-α and IL-1β levels. Berberine reduced sepsis-induced PEPCK and TLR4 mRNA overexpression in the liver.

Significance

This study demonstrated berberine inhibited TLR4-mediated hyperglycemia, insulin resistance and proinflammatory molecule production, thereby increasing ApoM gene expression and plasma ApoM. Berberine protected the damaged GVB via modulation of ApoM/S1P pathway.

中文翻译：

小ber碱通过调节ApoM / S1P途径在多菌性败血症模型中降低肠血管屏障通透性。

目的

肠血管屏障（GVB）的通透性过高在肠源性败血症中起作用。这项研究的目的是评估小碱是否可以改善肝载脂蛋白M（ApoM）的产生并提高血浆ApoM的水平来保护受损的GVB。

材料和方法

败血症诱导了受损的GVB。分别通过qRT-PCR和ELISA检测肝ApoM mRNA和磷酸烯醇丙酮酸羧激酶（PEPCK）mRNA和血浆ApoM水平。通过FITC-葡聚糖测定了体内毛细血管的通透性和大鼠肠道微血管内皮细胞（RIMEC）的通透性。用血糖仪检测血糖。ELISA法测定血浆胰岛素，TNF-α和IL-1β。用蛋白质印迹法检测RIMECs中的浆膜囊泡相关蛋白1（PV1），β-catenin和occludin。

主要发现

脓毒症降低了肝ApoM mRNA和血浆ApoM水平，但升高了肝PEPCK mRNA和血浆葡萄糖，胰岛素，TNF-α和IL-1β水平。体内重组大鼠ApoM或体外ApoM结合的S1P消除了增加的血管内皮通透性。ApoM结合的S1P降低了LPS处理的RIMEC中的PV1，但增加了occludin和β-catenin的表达。小Ber碱以剂量依赖性方式升高肝ApoM mRNA和血浆ApoM水平，但降低败血性高血糖症，胰岛素抵抗以及血浆TNF-α和IL-1β水平。小ber碱减少败血症诱导的肝中PEPCK和TLR4 mRNA的过度表达。