| 摘要: |
| ［摘要］ 目的 研究核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎症小体在高迁移率族核小体结合蛋白1（HMGN1）及其下游Toll样受体4（TLR4）-核因子κB（NF-κB）信号通路介导的急性肾损伤（AKI）中的调控作用。方法 选取C57BL/6小鼠18只，随机分为对照组、AKI组和细胞因子释放抑制药物3（CRID3）组（AKI+NLRP3抑制剂），每组6只。通过双侧肾蒂夹闭法建立缺血再灌注诱导的AKI小鼠模型。检测血清尿素氮（BUN）、肌酐（Scr）和胱抑素（cystatin C）水平以评估肾功能变化，通过苏木精-伊红（HE）染色、Masson染色和天狼星红染色观察肾组织病理变化，通过免疫组织化学染色和Western blot法检测肾组织中HMGN1、NLRP3和TLR4蛋白表达水平，通过酶联免疫吸附试验（ELISA）检测血清炎症因子白介素-1（IL-1）、白介素-6（IL-6）和肿瘤坏死因子α-（TNF-α）水平。结果 与对照组比较，AKI组血清BUN、Scr和cystatin C水平显著升高（P<0.05），肾组织病理损伤加重，出现肾小管坏死、间质纤维化和炎症细胞浸润，肾组织中HMGN1、NLRP3和TLR4蛋白表达显著升高（P<0.05），血清IL-1、IL-6和TNF-α水平显著升高（P<0.05）。与AKI组比较，CRID3组血清BUN、Scr和cystatin C水平显著降低（P<0.05），肾组织病理损伤、炎症和纤维化程度减轻，肾组织中HMGN1、NLRP3和TLR4蛋白表达显著降低（P<0.05），血清IL-1、IL-6和TNF-α水平显著降低（P<0.05）。结论 NLRP3通过调控HMGN1表达及下游TLR4信号通路参与AKI病理过程，可通过抑制NLRP3表达改善肾功能，减轻肾组织病理损伤和炎症反应。 |
| 关键词: 急性肾损伤 高迁移率族核小体结合蛋白1 炎症 细胞因子 炎症小体 |
| DOI：10.3969/j.issn.1674-3806.2025.12.07 |
| 分类号:R 692 |
| 基金项目:贵州省卫生健康委员会科学技术基金项目（编号：gzwkj2021-135）；贵州省科技计划项目（黔科合成果［2023］重大010）；2025年贵州省卫生健康委重点优势学科建设项目 |
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| Study on the role and molecular mechanism of HMGN1 in acute kidney injury based on the NLRP3 inflammatory pathway |
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LUO Yuhan1, SHAO Xingqin1, ZHANG Lang1, XIE Ying2, YUAN Jing2, ZHA Yan2, LIN Xin2
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1.Graduate School, Zunyi Medical University, Zunyi 563001, China; 2.Department of Nephrology, Guizhou Provincial People′s Hospital(Guizhou Provincial Key Laboratory for the Pathogenesis, Prevention and Treatment of Common Chronic Diseases), Guiyang 550002, China
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| Abstract: |
| ［Abstract］ Objective To study the regulatory role of NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome in acute kidney injury(AKI) mediated by high-mobility group nucleosome-binding protein 1(HMGN1) and its downstream Toll-like receptor 4(TLR4)-nuclear factor-kappa B(NF-κB) signaling pathways. Methods Eighteen C57BL/6 mice were selected and randomly divided into control group, AKI group and cytokine release inhibitory drug 3(CRID3) group(AKI+NLRP inhibitor), with 6 mice in each group. A mouse model of AKI induced by ischemia-reperfusion(I/R) was established by using the bilateral renal pedicle clamping method. The changes in renal function were evaluated by detecting the levels of serum blood urea nitrogen(BUN), serum creatinine(Scr) and cystatin C. The pathological changes in renal tissues were observed by using hematoxylin-eosin(HE) staining, Masson staining and Sirius Red staining. The expressions of HMGN1, NLRP3 and TLR4 in the renal tissues were detected by using immunohistochemical staining and Western blot method. The levels of inflammatory factors of interleukin-1(IL-1), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in serum were detected by using enzyme-linked immunosorbent assay(ELISA). Results Compared with those in the control group, the levels of serum BUN, Scr and cystatin C were significantly increased(P<0.05), and the pathological injuries of the renal tissues were aggravated, with renal tubular necrosis, interstitial fibrosis and inflammatory cell infiltration, and the expressions of HMGN1, NLRP3 and TLR4 proteins in the renal tissues were significantly increased(P<0.05), and the levels of serum IL-1, IL-6 and TNF-α were significantly increased in the AKI group(P<0.05). Compared with those in the AKI group, the levels of serum BUN, Scr and cystatin C were significantly decreased(P<0.05), and the pathological injuries, inflammation and fibrosis of the renal tissues were alleviated, and the expressions of HMGN1, NLRP3 and TLR4 proteins in the renal tissues were significantly decreased(P<0.05), and the levels of serum IL-1, IL-6 and TNF-α were significantly decreased in the CRID3 group(P<0.05). Conclusion NLRP3 participates in the pathological process of AKI by regulating the expression of HMGN1 and the downstream TLR4 signaling pathway. Inhibiting the expression of NLRP3 can improve renal function, alleviate pathological injuries and inflammatory response in renal tissues. |
| Key words: Acute kidney injury(AKI) High-mobility group nucleosome-binding protein 1(HMGN1) Inflammation Cytokines Inflammasome |
