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        Kir2.1在LPS或IL-4誘導(dǎo)的巨噬細(xì)胞M1/M2型極化中的作用*

        2022-03-28 05:59:12王璐楊瑞張瑩瑩李新芝馬克濤
        中國病理生理雜志 2022年3期
        關(guān)鍵詞:培養(yǎng)液孵育極化

        王璐, 楊瑞, 張瑩瑩, 李新芝, 馬克濤△

        · 論著 ·

        Kir2.1在LPS或IL-4誘導(dǎo)的巨噬細(xì)胞M1/M2型極化中的作用*

        王璐1,2,3, 楊瑞1,2,3, 張瑩瑩1,2,3, 李新芝1,2,4△, 馬克濤1,2,3△

        (1石河子大學(xué)醫(yī)學(xué)院新疆地方與民族高發(fā)病教育部重點(diǎn)實(shí)驗(yàn)室,新疆 石河子 832000;2石河子大學(xué)醫(yī)學(xué)院第一附屬醫(yī)院國家衛(wèi)健委中亞高發(fā)病防治重點(diǎn)實(shí)驗(yàn)室,新疆 石河子 832000;3石河子大學(xué)醫(yī)學(xué)院生理學(xué)教研室,新疆 石河子 832000;4石河子大學(xué)醫(yī)學(xué)院病理生理學(xué)教研室,新疆 石河子 832000)

        通過激活或阻斷內(nèi)向整流鉀通道2.1(inwardly-rectifying potassium channel 2.1, Kir2.1),檢測巨噬細(xì)胞M1/M2型極化標(biāo)志物及相關(guān)細(xì)胞因子的改變,探討Kir2.1在脂多糖(lipopolysaccharide, LPS)或白細(xì)胞介素4(interleukin-4, IL-4)誘導(dǎo)的巨噬細(xì)胞M1/M2型極化過程中的具體作用。采用RAW264.7小鼠巨噬細(xì)胞系,將未轉(zhuǎn)染慢病毒的RAW264.7細(xì)胞分為對(duì)照(control)組、LPS組、IL-4組、LPS+zacopride(Kir2.1選擇性激動(dòng)劑)組及IL-4+ML133(Kir2.1選擇性阻斷劑)組,將轉(zhuǎn)染慢病毒的RAW264.7細(xì)胞分為vector組、LPS+vector組、IL-4+vector組、KD-shKir2.1組、LPS+KD-shKir2.1組及IL-4+KD-shKir2.1組。應(yīng)用ELISA技術(shù)檢測巨噬細(xì)胞培養(yǎng)液上清中IL-1β、IL-6和腫瘤壞死因子α(tumor necrosis factor-α, TNF-α)的濃度;應(yīng)用實(shí)時(shí)熒光定量PCR技術(shù)檢測巨噬細(xì)胞中Kir2.1、誘導(dǎo)型一氧化氮合酶(inducible nitric oxide synthase, iNOS)、CD86、CD206、IL-6及TNF-α的mRNA表達(dá);應(yīng)用細(xì)胞免疫熒光技術(shù)和Western blot技術(shù)檢測巨噬細(xì)胞中Kir2.1、iNOS、CD86及CD206的定位和表達(dá)。Kir2.1在RAW264.7細(xì)胞的胞膜及胞質(zhì)中均有表達(dá),并且LPS干預(yù)RAW264.7細(xì)胞后Kir2.1的蛋白表達(dá)顯著下降(<0.01),IL-4干預(yù)巨噬細(xì)胞后Kir2.1的蛋白表達(dá)顯著升高(<0.01)。激活Kir2.1能夠顯著減少炎癥細(xì)胞因子的釋放(<0.05或<0.01),降低M1型極化標(biāo)志物iNOS和CD86的mRNA和蛋白表達(dá)(<0.05或<0.01),而阻斷或敲減Kir2.1能夠顯著增加炎癥細(xì)胞因子的釋放(<0.05或<0.01),升高M(jìn)1型極化標(biāo)志物iNOS和CD86的mRNA和蛋白表達(dá)(<0.05或<0.01),降低M2型極化標(biāo)志物CD206的mRNA和蛋白表達(dá)(<0.05或<0.01)。激活Kir2.1能夠抑制LPS誘導(dǎo)的巨噬細(xì)胞向M1型極化;而阻斷或敲減Kir2.1能夠促進(jìn)LPS誘導(dǎo)的巨噬細(xì)胞向M1型極化,抑制IL-4誘導(dǎo)的巨噬細(xì)胞向M2型極化。

        巨噬細(xì)胞極化;內(nèi)向整流鉀通道;炎癥;動(dòng)脈粥樣硬化

        動(dòng)脈粥樣硬化(atherosclerosis, AS)是一種以粥樣斑塊為特征的心血管疾?。?-3],巨噬細(xì)胞作為斑塊中炎癥因子的主要來源,能夠影響AS進(jìn)程及結(jié)局[4-6]。巨噬細(xì)胞在各種因素誘導(dǎo)下,能夠轉(zhuǎn)變?yōu)椴煌臉O化類型[7-8],即M1型巨噬細(xì)胞(經(jīng)典激活型巨噬細(xì)胞)和M2型巨噬細(xì)胞(替代激活型巨噬細(xì)胞),二者在各種因素調(diào)節(jié)下處于動(dòng)態(tài)平衡狀態(tài)[9-10]。同時(shí),巨噬細(xì)胞極化受多種鉀離子通道調(diào)節(jié),如內(nèi)向整流鉀離子通道(inwardly-rectifying potassium channels, Kir)等[11-12]。Kir2.1作為其中重要的成員之一,參與動(dòng)作電位復(fù)極化等過程[13-15]。有文獻(xiàn)報(bào)道,Kir2.1參與細(xì)胞分化,具有控制骨髓源性巨噬細(xì)胞增殖、活化和凋亡的作用[16-17]。因此,我們推測:Kir2.1可能通過調(diào)節(jié)脂多糖(lipopolysaccharide, LPS)或白細(xì)胞介素4(interleukin-4, IL-4)誘導(dǎo)的M1/M2型巨噬細(xì)胞極化,影響相關(guān)炎癥細(xì)胞因子的釋放,進(jìn)而影響AS進(jìn)展。為驗(yàn)證此假設(shè),本實(shí)驗(yàn)采用LPS或IL-4建立巨噬細(xì)胞極化模型,一方面給予Kir2.1選擇性阻斷劑ML133或選擇性激動(dòng)劑zacopride干預(yù),另一方面采用慢病毒轉(zhuǎn)染巨噬細(xì)胞以降低Kir2.1的表達(dá),應(yīng)用ELISA、實(shí)時(shí)熒光定量PCR、Western blot及細(xì)胞免疫熒光技術(shù),探討Kir2.1在LPS或IL-4誘導(dǎo)的M1/M2型巨噬細(xì)胞極化中的具體功能,闡明巨噬細(xì)胞的Kir2.1在病理生理過程中的作用。

        材料和方法

        1 主要試劑及儀器

        1.1試劑LPS(Sigma);IL-4(PeproTech);ML133和zacopride(APExBIO);抗Kir2.1抗體、抗誘導(dǎo)型一氧化氮合酶(inducible nitric oxide synthase, iNOS)抗體、抗CD86抗體和抗CD206抗體(Abcam);辣根過氧化物酶標(biāo)記的Ⅱ抗(北京中杉金橋生物技術(shù)有限公司)。

        1.2儀器生物安全柜[阿爾泰實(shí)驗(yàn)室設(shè)備(北京)有限公司];CO2恒溫培養(yǎng)箱(Thermo);LSM510激光共聚焦顯微鏡(Carl Zeiss)。

        2 方法

        2.1細(xì)胞培養(yǎng)RAW264.7小鼠巨噬細(xì)胞系來源于中國科學(xué)院上海細(xì)胞庫。將RAW264.7細(xì)胞用含有10%胎牛血清(fetal bovine serum, FBS)的DMEM培養(yǎng)液在37 ℃、5% CO2培養(yǎng)箱中孵育。將細(xì)胞分為control組、LPS組(100 μg/L LPS孵育24 h[18])、IL-4組(20 μg/L IL-4孵育24 h[19])、LPS+zacopride組(100 μmol/L zacopride預(yù)處理60 min后加入100 μg/L LPS共同孵育24 h)和IL-4+ML133組(20 μmol/L ML133預(yù)處理60 min后加入20 μg/L IL-4共同孵育24 h)。

        2.2慢病毒轉(zhuǎn)染用攜帶有綠色熒光蛋白(green fluorescent protein, GFP)標(biāo)記的空白對(duì)照慢病毒以及攜帶有GFP標(biāo)記小鼠shRNA的慢病毒(上海漢恒生物技術(shù)公司)感染RAW264.7細(xì)胞。實(shí)驗(yàn)分組為vector組(感染HBLV-GFP-PURO)、LPS+vector組(在vector組基礎(chǔ)上加入100 μg/L LPS孵育24 h)、IL-4+vector組(在vector組基礎(chǔ)上加入20 μg/L IL-4孵育24 h)、KD-shKir2.1組(感染HBLV-m-shRNA2-GFP-PURO)、LPS+KD-shKir2.1組(在KD-shKir2.1組基礎(chǔ)上加入100 μg/L LPS孵育24 h)和IL-4+KD-shKir2.1組(在KD-shKir2.1組基礎(chǔ)上加入20 μg/L IL-4孵育24 h)。

        2.3ELISA檢測培養(yǎng)液上清中IL-1β、IL-6和腫瘤壞死因子α(tumor necrosis factor-α, TNF-α)的濃度取傳代3~5次的RAW264.7細(xì)胞,鋪板干預(yù)后收集各組細(xì)胞培養(yǎng)液上清于EP管中并做好標(biāo)記,根據(jù)制造商說明書,應(yīng)用ELISA試劑盒檢測RAW264.7細(xì)胞培養(yǎng)液上清中IL-1β、IL-6和TNF-α的含量,每個(gè)樣品測定3次。

        2.4實(shí)時(shí)熒光定量PCR檢測巨噬細(xì)胞中Kir2.1、IL-6、TNF-α及M1/M2型極化標(biāo)志物的mRNA表達(dá)用標(biāo)準(zhǔn)Trizol試劑從RAW264.7細(xì)胞中提取總RNA。應(yīng)用20 μL反轉(zhuǎn)錄體系反轉(zhuǎn)錄合成cDNA,反應(yīng)程序?yàn)椋?5 ℃ 5 min,42 ℃ 60 min,70 ℃ 15 min,4 ℃。接著進(jìn)行實(shí)時(shí)熒光定量PCR,引物序列見表1。

        表1 引物序列

        F: forward; R: reverse.

        2.5Western blot檢測巨噬細(xì)胞中Kir2.1及M1/M2型極化標(biāo)志物的蛋白表達(dá)取出已干預(yù)好的細(xì)胞,PBS洗滌后于冰上裂解30 min,4 ℃、12 000 r/min離心15 min。采用BCA法測定蛋白濃度后,取蛋白樣品加入適量上樣緩沖液,于SDS聚丙烯酰胺凝膠進(jìn)行電泳分離,然后將凝膠上的蛋白轉(zhuǎn)移至PVDF膜上,5%脫脂奶粉室溫封閉2 h,分別加入Ⅰ抗4 ℃過夜,洗膜后再加入相應(yīng)Ⅱ抗室溫孵育2 h,再次洗膜后與發(fā)光試劑反應(yīng),置于X線膠片暗盒中曝光、顯影。應(yīng)用ImageJ 2x分析軟件檢測并分析條帶的灰度值。

        2.6細(xì)胞免疫熒光檢測巨噬細(xì)胞中Kir2.1及M1/M2型極化標(biāo)志物的定位和表達(dá)取出已干預(yù)好的細(xì)胞,PBS洗滌3次,固定,破膜,BSA于37 ℃封閉30 min,滴加Ⅰ抗于濕盒內(nèi)37 ℃孵育2 h,PBS漂洗3次,滴加Ⅱ抗,濕盒內(nèi)37 ℃孵育1 h,PBS漂洗3次,滴加DAPI避光染色,PBS漂洗3次,封片。激光掃描共焦顯微鏡觀察。

        3 統(tǒng)計(jì)學(xué)分析

        應(yīng)用SPSS 22.0分析軟件進(jìn)行統(tǒng)計(jì)學(xué)分析。所有實(shí)驗(yàn)數(shù)據(jù)均采用均數(shù)±標(biāo)準(zhǔn)差(mean±SD)表示。兩組間均數(shù)比較采用獨(dú)立樣本檢驗(yàn),多組間均數(shù)比較采用單因素方差分析(one-way ANOVA)。以<0.05為差異有統(tǒng)計(jì)學(xué)意義。

        結(jié)果

        1 LPS和IL-4能夠調(diào)節(jié)巨噬細(xì)胞中Kir2.1的蛋白表達(dá)和mRNA表達(dá)

        Kir2.1在巨噬細(xì)胞的胞膜及胞質(zhì)中均有表達(dá),LPS干預(yù)RAW264.7細(xì)胞后顯著降低了Kir2.1蛋白和mRNA的表達(dá)水平,而IL-4干預(yù)RAW264.7細(xì)胞后Kir2.1的蛋白和mRNA表達(dá)水平顯著提高(<0.01),見圖1。

        Figure 1.LPS and IL-4 regulated Kir2.1 expression in macrophages. A: the protein expression of Kir2.1 in RAW264.7 cells after LPS treatment; B: the protein expression of Kir2.1 in RAW264.7 cells after IL-4 treatment; C: the mRNA expression of Kir2.1 in RAW264.7 cells after LPS treatment; D: the mRNA expression of Kir2.1 in RAW264.7 cells after IL-4 treatment; E: the expression and localization of Kir2.1 in RAW264.7 cells (scale bar=50 μm). Mean±SD. n=6. **P<0.01 vs control group.

        2 激活Kir2.1抑制LPS誘導(dǎo)的巨噬細(xì)胞向M1型極化

        如圖2所示,經(jīng)LPS干預(yù)后,RAW264.7細(xì)胞IL-6、TNF-α、iNOS和CD86的mRNA表達(dá)水平,培養(yǎng)液上清中IL-1β、IL-6和TNF-α的濃度,以及iNOS和CD86的蛋白表達(dá)水平均顯著升高(<0.05或<0.01);與LPS組相比,LPS+zacopride組IL-6、TNF-α、iNOS和CD86的mRNA表達(dá)水平,培養(yǎng)液上清中IL-1β、IL-6和TNF-α的濃度,以及iNOS和CD86的蛋白表達(dá)水平均顯著降低(<0.05或<0.01)??梢?,激活Kir2.1能夠抑制LPS誘導(dǎo)的巨噬細(xì)胞向M1型極化。

        Figure 2.Activation of Kir2.1 inhibited LPS-induced polarization of macrophages to M1 phenotype. A to D: the mRNA expression of iNOS, CD86, IL-6 and TNF-α in RAW264.7 cells; E to G: the concentrations of IL-1β, IL-6 and TNF-α in culture supernatants of RAW264.7 cells; H: the protein expression of of iNOS and CD86 in RAW264.7 cells; I: the expression and localization of iNOS in RAW264.7 cells; J: the expression and localization of CD86 in RAW264.7 cells. Scale bar=50 μm Mean±SD. n=6. *P<0.05, **P<0.01 vs control group; #P<0.05, ##P<0.01 vs LPS group.

        3 敲減Kir2.1促進(jìn)LPS誘導(dǎo)的巨噬細(xì)胞向M1型極化

        如圖3A所示,未轉(zhuǎn)染慢病毒的control組無綠色熒光,而vector組和KD-shKir2.1組有綠色熒光,表明慢病毒已成功轉(zhuǎn)染RAW264.7細(xì)胞。為進(jìn)一步驗(yàn)證慢病毒敲減Kir2.1的效率,我們檢測了RAW264.7細(xì)胞中Kir2.1的mRNA和蛋白表達(dá)。與vector組相比,KD-shKir2.1組RAW264.7細(xì)胞中Kir2.1的mRNA和蛋白表達(dá)水平均顯著降低(<0.01),見圖3B、C。

        Figure 3.Verification of the transfection efficiency of lentivirus (A) and its knockdown efficiency for Kir2.1 (B and C). Scale bar=100 μm. Mean±SD. n=6. **P<0.01 vs vector group.

        如圖4所示,敲減Kir2.1能夠提高RAW264.7細(xì)胞培養(yǎng)液上清中IL-1β、IL-6和TNF-α水平,增加IL-6、TNF-α、iNOS和CD86的mRNA表達(dá),以及iNOS和CD86的蛋白表達(dá)(<0.05或<0.01),表明敲減Kir2.1能促進(jìn)LPS誘導(dǎo)的巨噬細(xì)胞向M1型極化。

        Figure 4.Knockdown of Kir2.1 promoted LPS-induced polarization of macrophages to M1 phenotype. A to D: the mRNA expression of iNOS, CD86, IL-6 and TNF-α in RAW264.7 cells; E to G: the concentrations of IL-1β, IL-6 and TNF-α in culture supernatants of RAW264.7 cells; H: the protein expression of iNOS and CD86 in RAW264.7 cells. Mean±SD. n=6. *P<0.05, **P<0.01 vs vector group; #P<0.05, ##P<0.01 vs LPS+vector group.

        4 阻斷或敲減Kir2.1抑制IL-4誘導(dǎo)的巨噬細(xì)胞向M2型極化

        CD206在RAW264.7細(xì)胞的胞膜和胞質(zhì)中均有表達(dá);RAW264.7細(xì)胞經(jīng)IL-4干預(yù)后,CD206的mRNA和蛋白表達(dá)顯著上調(diào)(<0.01);阻斷或敲減Kir2.1后,CD206的mRNA和蛋白表達(dá)顯著下調(diào)(<0.05或<0.01),見圖5。

        Figure 5.Blockage or knockdown of Kir2.1 inhibited IL-4-induced polarization of macrophages to M2 phenotype. A and B: the protein expression of CD206 in RAW264.7 cells after ML133 intervention or knockdown of Kir2.1; C and D: the mRNA expression of CD206 in RAW264.7 cells after ML133 intervention or knockdown of Kir2.1; E and F: the expression and localization of CD206 in RAW264.7 cells after ML133 intervention or knockdown of Kir2.1. Mean±SD. n=6. **P<0.01 vs control or vector group; #P<0.05, ##P<0.01 vs IL-4 or IL-4+vector group.

        討論

        AS是一種常見的慢性炎性疾病[20-21]。巨噬細(xì)胞不同的極化類型被認(rèn)為是AS斑塊發(fā)生發(fā)展的關(guān)鍵動(dòng)力[22-25]。巨噬細(xì)胞上有多種鉀離子通道表達(dá)[26]。目前已有研究,證實(shí)電壓門控性鉀通道1.3在巨噬細(xì)胞M1/M2型極化過程中發(fā)揮關(guān)鍵作用[27],但Kir2.1是否參與調(diào)節(jié)巨噬細(xì)胞M1/M2型極化尚不明確。本研究采用LPS和IL-4分別誘導(dǎo)構(gòu)建巨噬細(xì)胞M1和M2極化模型,探討Kir2.1是否通過調(diào)節(jié)巨噬細(xì)胞M1/M2型極化,影響炎癥細(xì)胞因子的釋放,進(jìn)而參與AS進(jìn)展。

        Kir2.1作為巨噬細(xì)胞中主要的離子通道之一,參與了巨噬細(xì)胞的分化和成熟。多項(xiàng)研究表明,Kir2.1在不同組織中調(diào)節(jié)巨噬細(xì)胞活化、增殖等多項(xiàng)生理功能[28-29],但Kir2.1在巨噬細(xì)胞M1/M2型極化過程中發(fā)揮的具體作用尚未明確報(bào)導(dǎo)。因此,本實(shí)驗(yàn)通過LPS或IL-4誘導(dǎo)巨噬細(xì)胞M1/M2型極化,觀察到Kir2.1主要表達(dá)在巨噬細(xì)胞的胞膜和胞質(zhì)中,并且LPS能夠下調(diào)巨噬細(xì)胞中Kir2.1的蛋白表達(dá),而IL-4能夠上調(diào)巨噬細(xì)胞中Kir2.1的蛋白表達(dá)。國內(nèi)外研究表明,zacopride作為一種Kir2.1選擇性激動(dòng)劑,能夠劑量依賴性地增強(qiáng)內(nèi)向整流鉀電流,在心血管疾病中具有關(guān)鍵性的保護(hù)作用[30-31]。Wang等[32]也檢測出ML133對(duì)Kir2.x家族的其他成員幾乎沒有選擇性,是迄今報(bào)道的具選擇性的Kir家族小分子阻斷劑。因此本研究采用zacopride激活Kir2.1,結(jié)果顯示激活Kir2.1能夠抑制巨噬細(xì)胞向M1型極化,另一方面采用ML133阻斷Kir2.1,顯示阻斷Kir2.1能夠抑制巨噬細(xì)胞向M2型極化。另有研究通過應(yīng)用轉(zhuǎn)染技術(shù)檢測到Kir2.1具有控制多種細(xì)胞類型電活動(dòng)的作用。本研究也通過慢病毒轉(zhuǎn)染巨噬細(xì)胞RAW264.7,觀察到敲減Kir2.1能夠促進(jìn)巨噬細(xì)胞向M1型極化,抑制巨噬細(xì)胞向M2型極化。

        綜上所述,本研究表明巨噬細(xì)胞中存在Kir2.1的表達(dá),激活Kir2.1可以抑制巨噬細(xì)胞向M1型極化,阻斷或敲減Kir2.1可抑制巨噬細(xì)胞向M2型極化并促進(jìn)巨噬細(xì)胞向M1型極化。這些結(jié)果表明,Kir2.1能夠調(diào)節(jié)巨噬細(xì)胞極化過程,由此推測上調(diào)Kir2.1對(duì)AS具有一定的緩解作用,但它具體通過哪些信號(hào)通路調(diào)節(jié)巨噬細(xì)胞極化尚不明確。目前考慮Kir2.1參與NF-κB信號(hào)通路和JAK/STAT信號(hào)通路并在其中發(fā)揮調(diào)節(jié)作用,因此后續(xù)研究將會(huì)從Kir2.1在這2條信號(hào)通路中的具體作用機(jī)制這一方面做進(jìn)一步探討。

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        [27] 劉雪琴, 王彥富, 張慧玲, 等. 動(dòng)脈粥樣硬化中鉀通道Kv1.3阻斷劑對(duì)巨噬細(xì)胞極化的影響[J]. 臨床心血管病雜志, 2016, 32(9):901-904.

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        Role of Kir2.1 in M1/M2 polarization of macrophages induced by LPS or IL-4

        WANG Lu1,2,3, YANG Rui1,2,3, ZHANG Ying-ying1,2,3, LI Xin-zhi1,2,4△, MA Ke-tao1,2,3△

        (1,,,832000,;2,,,832000,;3,,832000,;4,,832000,)

        To explore the specific role of inwardly-rectifying potassium channel 2.1 (Kir2.1) in the M1/M2 polarization of macrophage induced by lipopolysaccharide (LPS) or interleukin-4 (IL-4).Mouse RAW264.7 macrophages were used in this study. The RAW264.7 cells were divided into control group, LPS group, IL-4 group, LPS+zacopride (a selective agonist) group and IL-4+ML133 (a selective blocker of Kir2.1) group. The RAW264.7 cells infected with lentivirus were divided into vector group, LPS+vector group, IL-4+vector group, KD-shKir2.1 group, LPS+KD-shKir2.1 group and IL-4+KD-shKir2.1 group. The concentrations of IL-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the supernatant of macrophage medium were detected by ELISA. The mRNA levels of Kir2.1, inducible nitric oxide synthase (iNOS), CD86, CD206, IL-6 and TNF-α in the RAW264.7 cells were detected by real-time fluorescence quantitative PCR. The location and protein expression of Kir2.1, iNOS, CD86 and CD206 in the RAW264.7 cells were detected by immunofluorescence and Western blot.The Kir2.1 was mainly expressed in both membrane and cytoplasm of the RAW264.7 cells. The protein expression of Kir2.1 was significantly decreased after LPS intervention and significantly increased after IL-4 intervention in the RAW264.7 cells (<0.01). Activation of Kir2.1 significantly reduced the release of inflammatory cytokines (<0.05 or<0.01), decreased the mRNA and protein expression of iNOS and CD86 (<0.05 or<0.01). Inhibition of Kir2.1 significantly increased the release of inflammatory cytokines (<0.05 or<0.01) and the mRNA and protein levels of iNOS and CD86 (<0.05 or<0.01), but decreased the mRNA and protein expression of CD206 (<0.05 or<0.01).Activation of Kir2.1 inhibits the M1 polarization of LPS-induced macrophages. Inhibition of Kir2.1 promotes the M1 polarization of LPS-induced macrophages and decreases the M2 polarization of IL-4-induced macrophages.

        Macrophage polarization; Inwardly-rectifying potassium channels; Inflammation; Atherosclerosis

        R363; R541.4

        A

        10.3969/j.issn.1000-4718.2022.03.001

        1000-4718(2022)03-0385-09

        2021-09-23

        2022-01-20

        [基金項(xiàng)目]國家自然科學(xué)基金資助項(xiàng)目(No. 81860286);兵團(tuán)國際合作項(xiàng)目(No. 2020BC004);中國醫(yī)學(xué)科學(xué)院中央級(jí)公益性科研院所基本科研業(yè)務(wù)費(fèi)專項(xiàng)資金資助(No. 2020-PT330-003)

        馬克濤 Tel: 15001645180; E-mail: maketao@ hotmail.com; 李新芝 Tel:13309939180; E-mail: lixinzhi@shzu.edu.cn

        (責(zé)任編輯:盧萍,羅森)

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