茯苓酸调节MCP-1/CCR2信号通路对慢性肾小球肾炎大鼠炎症反应的影响

谢宇端, 李汉莲, 韩艳, 余婷, 李伟

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现代免疫学 ›› 2025, Vol. 45 ›› Issue (1) : 37-42.
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茯苓酸调节MCP-1/CCR2信号通路对慢性肾小球肾炎大鼠炎症反应的影响

  • 谢宇端1,李汉莲1,韩艳1,余婷2,李伟3
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Pachymic acid regulates inflammatory response in rats with chronic glomerulonephritis via the MCP-1/CCR2 signaling pathway

  • XIE Yu-duan1, LI Han-lian1, HAN Yan1, YU Ting2, LI Wei3
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摘要

为探讨茯苓酸(pachymic acid, PA)调节单核细胞趋化蛋白1(monocyte chemoattractant protein 1, MCP-1)/CC趋化因子受体2(CC chemokine receptor 2, CCR2)信号通路对慢性肾小球肾炎(chronic glomerulonephritis, CGN)大鼠炎症反应的影响,随机选择10只SD大鼠作为对照组,其余大鼠通过注射阳离子化牛血清白蛋白(cationic bovine serum albumin, C-BSA)造模。 将造模成功的大鼠随机分为CGN组、PA组(10 mg/kg PA)、GW0742组(0.3 mg/kg GW0742)、PA+GW0742组(10 mg/kg PA+0.3 mg/kg GW0742),每组10只。 采用试剂盒检测各组大鼠24 h尿蛋白、血清肌酐(serum creatinine, Scr)、血尿素氮(blood urea nitrogen, BUN)、抗氧化指标以及炎症指标;H-E染色检测肾组织病理损伤;免疫荧光染色检测肾小球IgG、C3水平;qRT-PCR检测MCP-1、CCR2 mRNA表达;Western blotting检测MCP-1/CCR2信号通路相关蛋白表达。 结果显示,对照组大鼠肾组织正常,CGN组大鼠毛细血管环和鲍曼囊均增厚,出现肾小管上皮细胞变性、炎症细胞浸润现象。 与对照组比较,CGN组大鼠24 h尿蛋白、Scr、BUN水平,IL-1β、TNF-α水平,肾组织损伤程度,IgG、C3荧光相对强度,MCP-1、CCR2 mRNA和蛋白表达水平均显著升高(P<0.05),超氧化物歧化酶(superoxide dismutase, SOD)、谷胱甘肽(glutathione, GSH)水平显著降低(P<0.05);PA改善了以上指标,而GW0742组与PA组变化趋势相反,GW0742减弱了PA对CGN大鼠炎症反应的改善效果。 该研究提示,PA可能通过下调MCP-1/CCR2信号通路改善CGN大鼠的炎症反应。 

Abstract

 The aim of this study is to investigate the impact of pachymic acid (PA) on inflammatory response in rats with chronic glomerulonephritis (CGN) by regulating monocyte chemoattractant protein 1(MCP-1)/CC chemokine receptor 2(CCR2) signaling pathway. Ten SD rats were randomly selected as the control group, and the rest were injected with cationic bovine serum albumin (C-BSA) to establish the CGN model. Successfully modeled rats were randomly divided into CGN group, PA group (10 mg/kg PA), GW0742 group (0.3 mg/kg GW0742), and PA+GW0742 group (10 mg/kg PA+0.3 mg/kg GW0742), with 10 rats in each group. 24-h urine protein, serum creatinine(Scr), blood urea nitrogen (BUN), antioxidant index and inflammatory index were detected with the corresponding commercial kits. The pathological injury of renal tissue was  detected by H-E staining, and the levels of IgG and C3 in glomerulus were detected by immunofluorescence staining. The mRNA expressions of MCP-1 and CCR2 were detected by qRT-PCR. Western blotting was used to detect the expressions of MCP-1/CCR2 signaling pathway related proteins. The results showed that rats in the control group had normal renal tissue whereas in the CGN group, both capillary rings and Bowman sacs were thickened, and degeneration of renal tubular epithelial cells and infiltration of inflammatory cells were observed. Compared to those of the control group, the levels of 24-h urine protein, Scr, and BUN, the levels of IL-1β and TNF-α, degree of renal tissue injury, fluorescence relative intensity of IgG and C3, and the mRNA and the protein levels of  MCP-1 and CCR2  in the CGN group significantly increased(P<0.05), while the levels of superoxide dismutase (SOD)and glutathione (GSH) significantly decreased (P<0.05). PA was shown to improve the above indicators, while GW0742 induced opposite changes of these indicators compared to those of the PA group. GW0742 attenuated the improvement effect of PA on inflammatory response in CGN rats. This study suggests that PA may improve the inflammatory response of CGN rats by down-regulating MCP-1/CCR2 signaling pathway.

关键词

茯苓酸 / 单核细胞趋化蛋白1/CC趋化因子受体2信号通路 / 慢性肾小球肾炎 / 炎症反应

Key words

pachymic acid / monocyte chemoattractant protein 1/CC chemokine receptor 2 signaling pathway / chronic glomerulonephritis / inflammatory response

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导出引用
谢宇端, 李汉莲, 韩艳, 余婷, 李伟. 茯苓酸调节MCP-1/CCR2信号通路对慢性肾小球肾炎大鼠炎症反应的影响. 现代免疫学. 2025, 45(1): 37-42
XIE Yu-duan, LI Han-lian, HAN Yan, YU Ting, LI Wei. Pachymic acid regulates inflammatory response in rats with chronic glomerulonephritis via the MCP-1/CCR2 signaling pathway. Current Immunology. 2025, 45(1): 37-42

基金

首都卫生发展科研专项项目(首发2022-1-4161)
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