| 邢艳雪,向一凡,赵帅,等.Fibulin-3调控 NOD1/RIP2信号通路对高血压合并脂代谢紊乱大鼠的效果及机制研究[J].安徽医药,2026,30(6):1120-1125. |
| Fibulin-3调控 NOD1/RIP2信号通路对高血压合并脂代谢紊乱大鼠的效果及机制研究 |
| Effect and mechanism of Fibulin-3 regulating NOD1/RIP2 signaling pathway on hypertensive rats complicated with lipid metabolism disorder |
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| DOI：10.3969/j.issn.1009-6469.2026.06.012 |
| 中文关键词: 高血压 脂代谢紊乱 Fibulin-3 核苷酸结合寡聚结构域 1(NOD1)/受体相互作用蛋白 2(RIP2)信号通路 肾素-血管紧张素 -醛固酮系统失衡 |
| 英文关键词: High blood pressure Disorder of lipid metabolism Fibulin-3 NOD1/RIP2 pathway Renin-angiotensin-aldoste. rone system imbalance |
| 基金项目:山东省优秀中青年科学家科研奖励基金项目( BS2021SW1209) |
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| 中文摘要: |
| 目的基于核苷酸结合寡聚结构域 1(NOD1)/受体相互作用蛋白 2(RIP2)通路探讨 Fibulin-3对高盐所导致的高血压合并脂代谢紊乱的效果及其可能的机制。方法该研究起止时间为 2023年 8月至 2024年 3月。从 40只 SD大鼠中采用抛硬币的方法选出 31只 SD大鼠建立高血压合并脂代谢紊乱模型，其余 9只大鼠作为空白组常规喂养；将造模成功的 27只大鼠采用抛硬币的方法分为模型组(高盐饲料 +含 6%氯化钠的水喂养 6周)、 Fibulin-3组(模型 +尾静脉注射 240 ng/kg Fibulin-3重组蛋白溶液)、 Fibulin-3+NOD1激动剂 C14-Tri-LAN-Gly组( C14-Tri-LAN-Gly组，模型 +尾静脉注射 240 ng/kg Fibulin-3重组蛋白溶液 +腹腔注射 0.05 g/L的 C14-Tri-LAN-Gly溶液 200 μL)，每组 9只。每周定期测量大鼠动脉血压，以苏木精 -伊红( HE)染色观察大鼠心肌组织病理情况，相应试剂盒检测脂代谢指标［甘油三酯( TG)、总胆固醇( TC)、高密度脂蛋白胆固醇( HDL-C)、低密度脂蛋白胆固醇( LDL-C)］、肾素 -血管紧张素 -醛固酮系统( RAAS)失衡指标［血管紧张素 Ⅰ(Ang Ⅰ)、血管紧张素 Ⅱ(Ang Ⅱ)、醛固酮］及炎症因子白细胞介素 -1β(IL-1β)、白细胞介素 -6(IL-6)含量变化，蛋白质印迹法检测 NOD1/RIP2通路蛋白及基质金属蛋白酶( MMP)-2、MMP-9蛋白表达。结果与空白组相比，模型组大鼠动脉血压、血管壁厚度、 TG、TC、LDL-C、Ang Ⅱ、醛固酮、 IL-1β、IL-6含量以及 MMP-2、MMP-9蛋白表达升高，而 HDL-C、Ang Ⅰ含量降低， NOD1和 RIP2蛋白表达升高( P<0.05)。给予 Fibulin-3干预后，模型大鼠上述病理指标的变化均得到了明显改善，同时 NOD1(胸主动脉: 0.81±0.06比 1.39±0.08，肝组织: |
| 英文摘要: |
| Objective To investigate the effect of fibulin-3 on high salt-induced hypertension combined with lipid metabolism disor. ders and its possible mechanism based on nucleotide-binding oligomerization domain 1 (NOD1)/receptor interacting protein 2 (RIP2) pathway.Methods The study period spanned from August 2023 to March 2024. Among 40 SD rats, 31 were selected by coin toss to es.tablish a model of hypertension combined with lipid metabolism disorder, while the remaining 9 rats served as the control group receiv.ing conventional feeding. The 27 rats that were successfully modeled were divided by coin toss into the model group (fed with high-salt diet and water containing 6% sodium chloride for 6 weeks), Fibulin-3 group (model tail vein injection of 240 ng/kg Fibulin-3 recombi. nant protein solution), Fibulin-3+NOD1 agonist C14-Tri-LAN-Gly group (C14-Tri-LAN-Gly group, model tail vein injection of 240 ng/ kg Fibulin-3 recombinant protein solution+intraperitoneal injection of 200 μL of 0.05 g/L C14-Tri-LAN-Gly solution). The arterialblood pressure was measured weekly. The pathological changes of myocardial tissue were observed by hematoxylin-eosin (HE) staining. The levels of lipid metabolism indexes [triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low densi. ty lipoprotein cholesterol (LDL-C)], renin-angiotensin-aldosterone system (RAAS) imbalance indexes [Angiotensin Ⅰ (Ang Ⅰ), Angio.tensin Ⅱ (Ang Ⅱ), aldosterone (ALD)] and inflammatory factors interleukin-1β (IL-1β) and interleukin-6 (IL-6) were detected with cor. responding kit, and the expressions of NOD1/RIP2 pathway proteins and matrix metallopeptidase 2 (MMP-2) and matrix metallopepti. dase 9 (MMP-9) proteins were analyzed by Western blot.Results Compared with the blank group, model group rats arterial blood pres. sure, blood vessel wall thickness, TG, TC, LDL-C, Ang Ⅱ, aldosterone, IL-1β, IL-6 levels and MMP-2, MMP-9 protein expression were increased, HDL-C and Ang Ⅰ levels were reduced, NOD1 and RIP2 protein expression were increased (P<0.05). After the intervention of Fibulin-3, the above pathological changes of the model rats were significantly improved, while the expressions of NOD1 (thoracic aor.ta: 0.81±0.06 vs. 1.39±0.08, liver tissue: 0.79±0.09 vs. 1.27±0.04) and RIP2 (thoracic aorta: 0.67±0.08 vs. 1.41±0.11, liver tissue: 0.73±0.06 vs. 1.34±0.08) proteins were inhibited (P<0.05), and the NOD1 agonist C14-Tri-LAN-Gly could partially reverse the improvement of Fibulin-3(P<0.05).Conclusion Fibulin-3 can improve vascular remodeling, blood pressure, lipid metabolism disorder and RAASimbalance in hypertensive rats with lipid metabolism disorder, the mechanism of which may be related to inhibiting NOD1/RIP2 path.way mediated inflammation. |
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