[1]郑明余,田园.基于TLR4/NF-κB信号通路探讨大黄酸对IgA肾病模型大鼠的影响[J].西部中医药,2024,37(08):15-20.[doi:10.12174/j.issn.2096-9600.2024.08.04]
　ZHENG Mingyu,TIAN Yuan.Study on the Effect of Rhein on IgA Nephropathy Rat Models via TLR4/NF-κB Signaling Pathway[J].Western Journal of Traditional Chinese Medicine,2024,37(08):15-20.[doi:10.12174/j.issn.2096-9600.2024.08.04]
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基于TLR4/NF-κB信号通路探讨大黄酸对IgA肾病模型大鼠的影响
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《西部中医药》[ISSN:2096-9600/CN:62-1204/R]

卷:
37
期数:
2024年08期
页码:
15-20
栏目:
基础研究
出版日期:
2024-08-15

文章信息/Info

Title:
Study on the Effect of Rhein on IgA Nephropathy Rat Models via TLR4/NF-κB Signaling Pathway
作者:
郑明余1, 田园2
1.临高县人民医院,海南 临高 571800
2.海南医学院第二附属医院,海南 海口 570100
Author(s):
ZHENG Mingyu1, TIAN Yuan2
1.Lingao County People's Hospital, Lingao 571800, China
2.The Second Affiliated Hospital of Hainan Medical University, Haikou 570100, China
关键词:
IgA肾病; 大黄酸; 纤维化; Toll样受体4/核因子B信号通路; 大鼠; 动物实验
Keywords:
IgA nephropathy; rhein; fibrosis; TLR4/NF-B signaling pathway; rat; zoopery
分类号:
R285.5
DOI:
10.12174/j.issn.2096-9600.2024.08.04
文献标志码:
A
摘要:
目的探讨大黄酸对免疫球蛋白A（immunoglobulin A，IgA）肾病大鼠Toll样受体4（Toll like receptor 4，TLR4）/核因子κB（Nuclear factor kappa-B，NF-κB）信号通路的影响。 方法选SPF级健康雄性SD大鼠75只，随机分为对照组15只和造模组60只。造模组采用牛血清白蛋白+脂多糖+蓖麻油+四氯化碳联合免疫建立IgA肾病模型，对照组大鼠在同时期采用相同方式给予等量0.9% NaCl处理。将造模成功大鼠随机分为模型组，大黄酸低、高剂量组及替米沙坦组，每组14只。模型组、对照组分别给予0.5%羧甲基纤维素钠；大黄酸低、高剂量组分别给予5、10 mg/mL大黄酸混悬液；替米沙坦组给予0.83 mg/mL替米沙坦混悬液。各组大鼠的灌胃剂量均为10 mL/kg，每日1次，连续8周。检测比较各组24 h尿蛋白量（24-hour urine protein，24h UTP）、血清肌酐（serum creatinine，SCr）、尿素氮（blood urea nitrogen，BUN）水平、肾组织IgA表达平均光密度值、肾组织病理损伤Katafuchi评分，以及肾组织TLR4、NF-κB p65、单核细胞趋化蛋白1（monocyte chemoattractant protein-1，MCP-1）、转化生长因子β1（transforming growth factor-β1，TGF-β1）表达水平。 结果与模型组比较，大黄酸低、高剂量组和替米沙坦组大鼠24 h UTP及血清SCr、BUN水平，肾组织IgA表达平均光密度值，肾组织病理损伤Katafuchi评分，肾组织TLR4、NF-κB p65、MCP-1、TGF-β1蛋白表达水平较低，差异均有统计学意义（P＜0.05），且大黄酸干预组呈现一定量效关系。 结论大黄酸能明显改善IgA肾病大鼠肾功能，减轻肾组织IgA沉积及病理损伤，且药物剂量越高，作用效果越好，其作用可能与抑制TLR4/NF-κB信号通路活性有关。
Abstract:
ObjectiveTo explore the influence of rhein on TLR4/NF-κB signaling pathway in IgA nephro-pathy rat models. MethodsAll 75 SPF-grade healthy male SD rats were selected and randomized into 15 rats in the control group and 60 ones in the modeling group. The modeling group adopted combined immunisation of bovine serum albumin+lipopolysaccharide + castor oil+carbon tetrachloride to eastablish IgA nephropathy models, the control group was treated with equivalent amounts of 0.9% Nacl in the same manner for the same period of time. After successfully modelling, the rats were randomized into the model group, low and high doses groups of rhein, and telmisartan group with 14 ones in each group. 0.5% sodium carboxymethylcellulose was given to the model group and the control group respectively; 5 mg/mL and 10 mg/mL rhein suspensions were administered to low and high doses groups of rhein; and telmisartan group received 0.83 mg/mL telmisartan. The intragastric dose was 10 mL/kg for different groups, once each day, for eight weeks consecutively. To detect and compare the levels of 24 h UTP, SCr and BUN, mean optical density of IgA expression in renal tissue, Katafuchi score of renal histopathologic injury, as well as the expressions of TLR4, NF-κB p65, MCP-1 and TGF-β1 in renal tissue in different groups. ResultsCompared with the model group, the levels of 24 h UTP, SCr and BUN, mean optical density of IgA expression in renal tissue, Katafuchi score of renal histopathologic injury, as well as the expressions of TLR4, NF-κB p65, MCP-1 and TGF-β1 in renal tissue were lower in low and high doses groups of rhein, and telmisartan group, and the difference had statistical meaning (P<0.05), and rhein intervention groups presented a certain dose-effect relationship. ConclusionRhein could apparently improve renal function in IgA nephropathy rats, reduce IgA deposition in renal tissue and relieve pathological injury, the higher the dose of the medicine was, the better the effects were, and its mechanism might be related to inhibiting the activity of TLR4/NF-κB signaling pathway.

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备注/Memo

备注/Memo:
郑明余（1984—），男，主治医师。研究方向：肾脏病的中医药治疗。海南省自然科学基金（814342）。
更新日期/Last Update: 2024-08-15