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嗜酸乳杆菌 KBL409 通过免疫调节作用减轻慢性肾脏病小鼠的肾脏纤维化。

Lactobacillus acidophilus KBL409 Reduces Kidney Fibrosis via Immune Modulatory Effects in Mice with Chronic Kidney Disease.

机构信息

Division of Nephrology, Soonchunhyang University Seoul Hospital, Seoul, 04401, Republic of Korea.

Graduate School, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.

出版信息

Mol Nutr Food Res. 2022 Nov;66(22):e2101105. doi: 10.1002/mnfr.202101105. Epub 2022 Sep 14.

Abstract

SCOPE

Intestinal dysbiosis has been reported to play an important role in the pathogenesis of various diseases, including chronic kidney disease (CKD). Here, to evaluate whether probiotic supplements can have protective effects against kidney injury in an animal model of CKD is aimed.

METHODS AND RESULTS

An animal model of CKD is established by feeding C57BL/6 mice a diet containing 0.2% adenine. These model mice are administered Lactobacillus acidophilus KBL409 daily for 4 weeks. Features of adenine-induce CKD (Ade-CKD) mice, such as prominent kidney fibrosis and higher levels of serum creatinine and albuminuria are improved by administration of KBL409. Ade-CKD mice also exhibit a disrupted intestinal barrier and elevate levels of TNF-α, IL-6, and 8-hydroxy-2'-deoxyguanosine. These changes are attenuated by KBL409. Administration of KBL409 significantly reduces macrophage infiltration and promotes a switch to the M2 macrophage phenotype and increasing regulatory T cells. Notably, the NLRP3 inflammasome pathway is activated in the kidneys of Ade-CKD and decreases by KBL409. In primary kidney tubular epithelial cells treated with p-cresyl sulfate, short-chain fatty acids significantly increase M2 macrophage polarization factors and decrease profibrotic markers.

CONCLUSIONS

These results demonstrate that supplementation with the probiotic KBL409 has beneficial immunomodulating effects and protects against kidney injury.

摘要

范围

肠道菌群失调已被报道在各种疾病的发病机制中发挥重要作用,包括慢性肾脏病(CKD)。在这里,旨在评估益生菌补充剂是否可以对 CKD 动物模型中的肾损伤具有保护作用。

方法和结果

通过用含有 0.2%腺嘌呤的饮食喂养 C57BL/6 小鼠来建立 CKD 动物模型。这些模型小鼠每天给予嗜酸乳杆菌 KBL409 治疗 4 周。KBL409 改善了腺嘌呤诱导的 CKD(Ade-CKD)小鼠的特征,如明显的肾脏纤维化和更高水平的血清肌酐和蛋白尿。Ade-CKD 小鼠还表现出肠道屏障破坏和 TNF-α、IL-6 和 8-羟基-2'-脱氧鸟苷水平升高。这些变化通过 KBL409 得到减弱。KBL409 的给药显著减少了巨噬细胞浸润,并促进了 M2 巨噬细胞表型的转换和调节性 T 细胞的增加。值得注意的是,NLRP3 炎性小体途径在 Ade-CKD 的肾脏中被激活,并且通过 KBL409 减少。在用 p- 对甲酚硫酸盐处理的原代肾小管上皮细胞中,短链脂肪酸显著增加 M2 巨噬细胞极化因子并减少促纤维化标志物。

结论

这些结果表明,益生菌 KBL409 的补充具有有益的免疫调节作用并可防止肾损伤。

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