Kv1.3抑制剂玛格斑蝎毒素对肾损伤模型小鼠M1型巨噬细胞极化及肾脏炎症和损伤的影响  

Effects of Kv1.3 inhibitor margatoxin on polarization of M1 macrophages and renal inflammation and injury in mice with renal injury

作　　者：孔佳伟 李莎莎[2] 刘其锋[1] KONG Jiawei;LI Shasha;LIU Qifeng(Department of Nephrology,Affiliated Kunshan Hospital of Jiangsu University,Suzhou Jiangsu 215300,China;Clinical Research&Lab Center,Affiliated Kunshan Hospital of Jiangsu University,Suzhou Jiangsu 215300,China)

机构地区：[1]江苏大学附属昆山医院肾脏内科,江苏苏州215300 [2]江苏大学附属昆山医院临床试验研究中心,江苏苏州215300

出　　处：《江苏大学学报(医学版)》2025年第1期13-20,共8页Journal of Jiangsu University:Medicine Edition

基　　金：江苏省卫生健康委2023年度医学科研立项项目(Z2023039)。

摘　　要：目的:观察电压门控钾离子通道亚型(voltage-gated potassium channel isoform,Kv)1.3抑制剂玛格斑蝎毒素(margatoxin,MgTx)对单侧输尿管梗阻(unilateral ureteral obstruction,UUO)小鼠巨噬细胞(macrophage,M)极化及肾脏炎症和损伤的影响。方法:将48只雄性C57BL/6J小鼠随机均分为4组:假手术(Sham)组、Sham+MgTx组、UUO组、UUO+MgTx组,每组12只;Sham组行单纯开腹及关腹手术,术后每日腹腔注射生理盐水,Sham+MgTx组行开腹及关腹手术,术后每日腹腔注射MgTx,UUO组行UUO手术,术后每日腹腔注射生理盐水,UUO+MgTx组行UUO手术,术后每日腹腔注射MgTx。分别于术后第3天、第7天每组麻醉6只小鼠,眼球采血留取外周血,然后立即处死小鼠并收集肾组织;采用HE染色评估肾脏损伤程度;蛋白免疫印迹法检测肾组织中Kv1.3及转化生子因子-β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)表达;流式细胞术分析外周血单核细胞的改变及肾组织中M极化情况;qRT-PCR检测肾组织M1型及M2型M标志物相关mRNA相对表达量。结果:与Sham组相比,UUO组可见明显的肾损伤及炎症反应,Kv1.3、TGF-β1、α-SMA相对表达水平明显升高(P<0.001);与UUO组相比,UUO+MgTx组肾损伤明显减轻,Kv1.3、TGF-β1、α-SMA相对表达水平明显降低(P<0.001)。此外,与Sham组相比,UUO组外周血单核细胞及肾组织中M1型M比例明显升高(P<0.01),M1型M标志物相关mRNA相对表达量明显升高(P<0.01),M2型M标志物相关mRNA相对表达量明显降低(P<0.01);与UUO组相比,UUO+MgTx组外周血单核细胞比例及肾组织中M1型M比例明显降低(P<0.01),M1型M标志物mRNA相对表达量显著降低(P<0.01),M2型M标志物mRNA水平显著升高(P<0.01)。结论:Kv1.3抑制剂MgTx可抑制UUO小鼠M向M1极化,减轻肾脏炎症和损伤。Objective:To observe the effect of voltage-gated potassium channel isoform(Kv)1.3 inhibitor,margatoxin(MgTx),on macrophage(M)polarization and renal inflammation and injury in mice with unilateral ureteral obstruction(UUO).Methods:Forty-eight male C57BL/6J mice were randomly and equally divided into four groups:Sham group,Sham+MgTx group,UUO group,UUO+MgTx group,with 12 mice in each group.The Sham group underwent simple open and closed abdominal surgery,with daily intraperitoneal injection of noraml saline after operation;Sham+MgTx group underwent open and closed abdominal surgery,with daily intraperitoneal injection of MgTx after surgery;UUO group underwent UUO operation,with daily intraperitoneal injection of normal saline after operation;UUO+MgTx group underwent UUO operation,with daily intraperitoneal injection of MgTx after operation.On the 3rd and 7th day after operation,six mice in each group were anesthetized,and whole blood was collected from the eyeballs,then the mice were immediately euthanized and kidney tissue was harvested.Renal injury was assessed by HE staining;protein levels of Kv1.3,TGF-β1 andα-SMA were detected by Western blotting;changes of peripheral blood monocytes and renal M polarization were analyzed by flow cytometry;mRNA levels of M1 and M2 biomarkers were detected by qRT-PCR.Results:Compared with Sham group,UUO group showed obvious renal injury and inflammation,and the relative expression levels of Kv1.3,TGF-β1,α-SMA were significantly increased(P<0.001).Compared with UUO group,renal injury was reduced,and relative expression levels of Kv1.3,TGF-β1 andα-SMA were greatly decreased in UUO+MgTx group(P<0.001).In addition,compared with Sham group,the proportion of M1 type M in peripheral blood monocytes and kidney tissues,and the relative expression level of M1 type M marker related mRNA weresignificantly increased(P<0.01),while the relative expression level of M2 type M marker related mRNA were obviously decreased in UUO group(P<0.01).Compared with UUO group,the proportion of periphe

关 键 词：电压门控钾离子通道亚型1.3 玛格斑蝎毒素 巨噬细胞 极化 肾脏损伤 单侧输尿管梗阻 

分 类 号：R692.2[医药卫生—泌尿科学]