不同剂量羟氯喹对IgA肾病大鼠肠道菌群结构及糖基转移酶活性的影响

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology Pub Date : 2025-03-12 DOI:10.1016/j.imbio.2025.152891

Lingling Bao, Xueyan Bian, Liling Ren, Sizeng Bao, Aiwei Zhang

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引用次数: 0

摘要

背景：羟氯喹（HCQ）由于其减少蛋白尿的能力，是免疫球蛋白A肾病（IgAN）的一种替代疗法。本研究探讨了不同剂量的HCQ对IgAN大鼠肠道菌群结构和糖基转移酶活性的影响。方法以牛血清白蛋白、蓖麻油、脂多糖处理的sigan模型大鼠分别灌胃HCQ（18、36 mg/kg）。然后观察大鼠尿红细胞数和肾功能的变化。采用ELISA法检测血清中半乳糖缺乏IgA1 （Gd-IgA1）、B细胞活化因子（BAFF）、c反应蛋白（CRP）水平及肾组织炎症因子水平。采用组织学方法观察肾组织损伤及IgA沉积情况。采用qRT-PCR、Western blot或体外酶法检测core1 β - 1,3-半乳糖转移酶（C1GALT1）、core1合成酶特异性分子伴侣（COSMC）和ST6 n -乙酰半乳糖胺α -2,6-唾液转移酶2 （ST6GALNAC2）的表达。采用16s rDNA测序法分析大鼠肠道菌群结构。结果shcq呈剂量依赖性降低血清肌酐、尿素、Gd-IgA1、BAFF、CRP和尿蛋白水平，减少尿红细胞数量，抑制肾组织炎症因子表达和IgA沉积，上调外周血单核细胞C1GALT1、COSMC表达，下调ST6GALNAC2表达。结论hcq能减轻IgAN大鼠肾小球系膜区肿胀，改善肠道菌群失衡。

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Different doses of hydroxychloroquine regulate the structure of intestinal flora and glycosyltransferase activity in rats with IgA nephropathy

Background

Hydroxychloroquine (HCQ), by virtue of its ability to reduce proteinuria, is an alternative therapy for Immunoglobulin A nephropathy (IgAN). This study investigated the effects of different doses of HCQ on the structure of intestinal flora and glycosyltransferase activity in IgAN rats.

Methods

IgAN model rats constructed by treatment of bovine serum albumin, castor oil and lipopolysaccharide were administered with HCQ (18 or 36 mg/kg) by gavage. Then the number of urine erythrocyte and the renal function of rats were evaluated. The levels of galactose-deficient IgA1 (Gd-IgA1), B cell activation factor (BAFF) and C-reactive protein (CRP) in serum and those of inflammatory factors in renal tissue were detected by ELISA. Renal tissue injury and IgA deposition were assessed by histological analysis. The expressions of Core 1 beta1,3-galactosyltransferase (C1GALT1), Core 1 synthase specific molecular chaperone (COSMC) and ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2) were quantified by qRT-PCR, Western blot or in vitro enzyme assays. 16 s rDNA sequencing was used to analyze the structure of intestinal flora in rats.

Results

HCQ dose-dependently decreased the levels of serum creatinine, UREA, Gd-IgA1, BAFF, CRP and urine protein, waned the number of urine erythrocyte, inhibited the expressions of inflammatory factors and IgA deposition in renal tissue, and up-regulated the expressions of C1GALT1, COSMC and down-regulated ST6GALNAC2 expression in peripheral blood mononuclear cells (PBMCs).

Conclusion

HCQ could reduce glomerular swelling in mesangial area and improve the imbalance of intestinal flora in IgAN rats.

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来源期刊

Immunobiology 医学-免疫学

CiteScore

5.00

自引率

3.60%

发文量

108

审稿时长

55 days

期刊介绍： Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.