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小檗碱对 LPS 诱导的肠损伤的保护作用:综述。

Protective effect of berberine against LPS-induced injury in the intestine: a review.

机构信息

Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Medical Toxicology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Cell Cycle. 2022 Nov;21(22):2365-2378. doi: 10.1080/15384101.2022.2100682. Epub 2022 Jul 19.

Abstract

Sepsis is a systemic inflammatory condition caused by an unbalanced immunological response to infection, which affects numerous organs, including the intestines. Lipopolysaccharide (LPS; also known as endotoxin), a substance found in Gram-negative bacteria, plays a major role in sepsis and is mostly responsible for the disease's morbidity and mortality. Berberine is an isoquinoline alkaloid found in a variety of plant species that has anti-inflammatory properties. For many years, berberine has been used to treat intestinal inflammation and infection. Berberine has been reported to reduce LPS-induced intestinal damage. The potential pathways through which berberine protects against LPS-induced intestinal damage by inhibiting NF-κB, suppressing MAPK, modulating ApoM/S1P pathway, inhibiting COX-2, modulating Wnt/Beta-Catenin signaling pathway, and/or increasing ZIP14 expression are reviewed. LPS, lipopolysaccharide; TLR, Toll-like receptor; MD-2, myeloid differentiation factor 2; CD14, cluster of differentiation 14; LBP, lipopolysaccharide-binding protein; MYD88, myeloid differentiation primary response 88; NF-κB, nuclear factor kappa light-chain enhancer of activated B cells; MAPK, mitogen-activated protein kinase; IL, interleukin; TNFα, tumor necrosis factor-alpha; Caco-2, cyanocobalamin uptake by human colon adenocarcinoma cell line; MLCK, myosin light-chain kinase; TJ, tight junction; IκBα, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; IBS, irritable bowel syndrome; ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase (JNK; GVB, gut-vascular barrier; ApoM, apolipoprotein M; S1P, sphingosine-1-phosphate; VE-cadherin, vascular endothelial cadherin; AJ, adherens junction; PV1, plasmalemma vesicle-associated protein-1; HDL, high-density lipoprotein; Wnt, wingless-related integration site; Fzd, 7-span transmembrane protein Frizzled; LRP, low-density lipoprotein receptor-related protein; TEER, transendothelial/transepithelial electrical resistance; COX-2, cyclooxygenase-2; iNOS, inducible nitric oxide synthase; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor-binding protein; ZIP, Zrt-Irt-like protein; PPAR, peroxisome proliferator-activated receptors; p-PPAR, phosphorylated-peroxisome proliferator-activated receptors; ATF, activating transcription factors; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; SARA, subacute ruminal acidosis; IPEC-J2, porcine intestinal epithelial cells; ALI, acute lung injury; ARDS, acute respiratory distress syndrome.

摘要

脓毒症是一种全身性炎症性疾病,由感染引起的免疫反应失衡引起,它影响许多器官,包括肠道。脂多糖(LPS;也称为内毒素)是革兰氏阴性细菌中发现的一种物质,在脓毒症中起着重要作用,是该病发病率和死亡率的主要原因。小檗碱是一种存在于多种植物物种中的异喹啉生物碱,具有抗炎特性。多年来,小檗碱一直被用于治疗肠道炎症和感染。据报道,小檗碱可减少 LPS 诱导的肠道损伤。本文综述了小檗碱通过抑制 NF-κB、抑制 MAPK、调节 ApoM/S1P 通路、抑制 COX-2、调节 Wnt/β-连环蛋白信号通路和/或增加 ZIP14 表达来防止 LPS 诱导的肠道损伤的潜在途径。LPS,脂多糖;TLR,Toll 样受体;MD-2,髓样分化因子 2;CD14,分化簇 14;LBP,脂多糖结合蛋白;MYD88,髓样分化初级反应 88;NF-κB,核因子 kappa 轻链增强子 B 细胞激活物;MAPK,丝裂原活化蛋白激酶;IL,白细胞介素;TNFα,肿瘤坏死因子-α;Caco-2,人结肠腺癌细胞系对氰钴胺素的摄取;MLCK,肌球蛋白轻链激酶;TJ,紧密连接;IκBα,核因子 kappa 轻链基因增强子 B 细胞抑制剂,α;IBS,肠易激综合征;ERK,细胞外信号调节激酶;JNK,c-Jun N 末端激酶(JNK;GVB,肠道-血管屏障;ApoM,载脂蛋白 M;S1P,鞘氨醇-1-磷酸;VE-cadherin,血管内皮钙黏蛋白;AJ,黏附连接;PV1,质膜小泡相关蛋白-1;HDL,高密度脂蛋白;Wnt,无翅型整合位点;Fzd,7 跨膜蛋白 Frizzled;LRP,低密度脂蛋白受体相关蛋白;TEER,跨内皮/跨上皮电阻;COX-2,环氧化酶-2;iNOS,诱导型一氧化氮合酶;IGF,胰岛素样生长因子;IGFBP,胰岛素样生长因子结合蛋白;ZIP,Zrt-Irt 样蛋白;PPAR,过氧化物酶体增殖物激活受体;p-PPAR,磷酸化过氧化物酶体增殖物激活受体;ATF,激活转录因子;SOD,超氧化物歧化酶;GSH-Px,谷胱甘肽过氧化物酶;SARA,亚急性瘤胃酸中毒;IPEC-J2,猪肠上皮细胞;ALI,急性肺损伤;ARDS,急性呼吸窘迫综合征。

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