Clodronate Liposomes巨噬細(xì)胞清除劑氯膦酸鹽脂質(zhì)體在PAB模型中的應(yīng)用

右心室（RV）功能障礙會增加猝死風(fēng)險，在小鼠中研究了對右心室壓力應(yīng)激的反應(yīng)。在肺動脈縮窄引起的壓力超負(fù)荷后積聚在右心室的免疫細(xì)胞中，荷蘭Liposoma巨噬細(xì)胞細(xì)胞清除劑清除單核巨噬細(xì)胞會導(dǎo)致嚴(yán)重心律失常引發(fā)的猝死。心臟巨噬細(xì)胞通過通過縫隙連接促進(jìn)心肌細(xì)胞間的通信，對維持心臟沖動傳導(dǎo)至關(guān)重要。心臟巨噬細(xì)胞產(chǎn)生的兩性表皮生長因子（AREG）是調(diào)控心肌細(xì)胞中連接蛋白43磷酸化及轉(zhuǎn)位的關(guān)鍵介質(zhì)。從巨噬細(xì)胞中刪除Areg會導(dǎo)致縫隙連接紊亂，進(jìn)而在急性應(yīng)激狀態(tài)下（包括右心室壓力超負(fù)荷和β-腎上腺素能受體激動）引發(fā)致命性心律失常。這些結(jié)果表明，來自心臟常駐巨噬細(xì)胞的AREG是心臟沖動傳導(dǎo)的關(guān)鍵調(diào)節(jié)因子，并可能成為預(yù)防猝死的有效治療靶點。Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除肝臟和腫瘤巨噬細(xì)胞，疾病模型為：肺動脈環(huán)縮術(shù)(pulmonary artery banding, PAB)模型。Pulmonary artery banding (PAB) 是通過環(huán)束帶限制肺動脈血流的姑息性手術(shù)，主要用于治療先天性心臟病，如室間隔缺損、大動脈轉(zhuǎn)位等伴隨過度肺血流的疾病。 ?原理: 該手術(shù)通過聚四氟乙烯帶環(huán)束肺動脈主干，降低肺動脈壓力和血流量，緩解心臟負(fù)擔(dān)。早期作為復(fù)雜先心病分期治療的過渡手段，現(xiàn)僅用于多發(fā)性室間隔缺損、合并主動脈縮窄等特殊病例。荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications：心臟巨噬細(xì)胞在心臟壓力期間防止猝死。

論文信息：

論文題目：Cardiac macrophages prevent sudden death during heart stress

期刊名稱：Nature Communications

時間期卷：12, Article number: 1910 (2021)

在線時間：2021年3月26日

DOI：doi.org/10.1038/s41467-021-22178-0

產(chǎn)品信息：

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes& Control liposomes

辦事處：Target Technology(靶點科技)

清除效果：

小鼠肺動脈環(huán)縮術(shù)(pulmonary artery banding, PAB)模型造模，使用荷蘭Liposoma巨噬細(xì)胞細(xì)胞清除劑清除單核巨噬細(xì)胞；抗體清除粒細(xì)胞；CD4 敲除小鼠（無CD4 T細(xì)胞），CD8敲除小鼠（無CD8 T細(xì)胞），Rag2小鼠（無成熟T和B細(xì)胞）。如下圖，造模后，巨噬細(xì)胞大量增多，使用荷蘭Clodronate Liposomes可以有效清除巨噬細(xì)胞，同時，清除巨噬細(xì)胞后，小鼠很快大量死亡。提示巨噬細(xì)胞在PAB模型里面的保護(hù)作用。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法文字描述：

Animal studies

Male C57BL6/J mice were purchased from CLEA Japan and Jackson Laboratory and maintained on a standard mouse chow diet under sterile barrier conditions, on a 12-h light-dark cycle with 18–23?°C and 40–60% humidity. Male Areg homozygous null (Areg?/?) mice were backcrossed to C57BL6/J mice over ten generations. Rag2?/?, Cd4?/?, and Cd8a?/? mice were purchased from Taconic (Germantown, NY). The genotypes of all mice were determined using genomic PCR. The isoproterenol challenge entailed bolus administration of isoproterenol (Sigma) 5?mg/kg intraperitoneally under constant ECG recording. Clodronate liposomes and control liposomes were purchased from LIPOSOMA B.V. A total of 10?μl of clodronate or control liposome solution per gram of mouse were intravenously administrated 24?h before PAB. After the first administration of clodronate or control liposomes, the same volume of liposomes was also administrated every 7 days for long term depletion, per the manufacturer’s instructions. All protocols for animal experiments were approved by the Animal Care and Use Committee of the University of Tokyo.

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法文獻(xiàn)截圖：