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ω-3 多不饱和脂肪酸对腹膜透析大鼠肠道损伤及巨噬细胞极化的保护作用及机制。

Protective effects and mechanisms of omega-3 polyunsaturated fatty acid on intestinal injury and macrophage polarization in peritoneal dialysis rats.

机构信息

Department of Nutrition, The Second Xiangya Hospital, Central South University, Changsha, China.

Institute of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, China.

出版信息

Nephrology (Carlton). 2019 Oct;24(10):1081-1089. doi: 10.1111/nep.13587. Epub 2019 Apr 4.

Abstract

AIM

This study was conducted to investigate the chronic injury of peritoneal glucose injection on the peritoneum and intestine and the protective effects of omega-3 polyunsaturated fatty acid (ω-3PUFA) during peritoneal dialysis (PD).

METHODS

Peritoneal dialysis animal models were established by intraperitoneal injection of 4.25% glucose for 28 days. Protein expression in ileum and peritoneum was measured by immunofloresence and immunohistochemistry. Protein expression in macrophages was measured by Western blot. Fibrosis was analyzed by Masson staining.

RESULTS

Peritoneal dialysis significantly increased the structural injury and decreased junction-related protein ZO-1 and occludin expression in ileum, the expression of proteins relating to the activation of M2 (Erg2, IRF4), but not M1 (CD38, IRF5) macrophages. PD significantly increased the expression of TGF-β1, VEGF and ALK5 protein in peritoneal tissues. PD significantly increased fibrosis (Masson staining) and the expression of fibroblast marker α-SMA in peritoneal tissues. Injection of macrophage clean reagent and ω-3PUFA significantly inhibited M2 activation, and decreased Masson staining, α-SMA, TGF-β1, VEGF and ALK5 protein expression in peritoneal tissues in PD treated rats. ω-3PUFA injection significantly decreased PD-induced injury in ileum and normalized the expression of ZO-1 and occludin in the ileum of PD rats.

CONCLUSION

Omega-3 fatty acids can provide a protective role on PD-induced peritoneal fibrosis and injury of the intestine.

摘要

目的

本研究旨在探讨腹腔内葡萄糖注射对腹膜和肠道的慢性损伤以及ω-3 多不饱和脂肪酸(ω-3PUFA)在腹膜透析(PD)过程中的保护作用。

方法

通过腹腔内注射 4.25%葡萄糖建立腹膜透析动物模型,28 天后测量回肠和腹膜中的蛋白表达。通过免疫荧光和免疫组化测量巨噬细胞中的蛋白表达。通过 Western blot 测量纤维化程度。

结果

PD 显著增加了回肠的结构损伤,并降低了连接相关蛋白 ZO-1 和 occludin 的表达,同时增加了 M2(Erg2、IRF4)而不是 M1(CD38、IRF5)巨噬细胞的相关蛋白表达。PD 显著增加了腹膜组织中 TGF-β1、VEGF 和 ALK5 蛋白的表达。PD 显著增加了腹膜组织中的纤维化(Masson 染色)和纤维母细胞标志物 α-SMA 的表达。巨噬细胞清除试剂和 ω-3PUFA 的注射显著抑制了 M2 的激活,并降低了 PD 治疗大鼠腹膜组织中的 Masson 染色、α-SMA、TGF-β1、VEGF 和 ALK5 蛋白的表达。ω-3PUFA 的注射显著降低了 PD 诱导的回肠损伤,并使 PD 大鼠回肠中 ZO-1 和 occludin 的表达正常化。

结论

ω-3 脂肪酸对 PD 诱导的腹膜纤维化和肠道损伤具有保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e6/6790651/26a6246165a8/NEP-24-1081-g001.jpg

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