【摘要】 目的探索IL-6介导的早期炎症在新生小鼠心脏再生中的作用及其机制。方法新生1 d的小鼠随机分为模型组和假手术组,前者低温麻醉切除心尖成模,后者只作开胸缝合。术后1、3、7和21 d摘取心脏。石蜡切片后H&E染色,q PCR检测增殖相关基因表达;并检测炎症因子基因il-6、il-1β及icam1转录水平的变化。ELISA检测血清中IL-6、TNF-α及IL-1β的含量,Western blot检测IL-6下游底物Akt、Akt(S473)、Stat3、Stat3(T705)的表达量,并检测Akt和Stat3磷酸化负向调控基因PP2A的变化。结果术后7 d模型组小鼠基本完成心脏再生过程,切片染色显示再生心脏的心尖结构完整,心肌细胞增殖相关基因表达增加。IL-6、TNF-α及IL-1β等炎症因子在术后早期急剧升高,其下游底物Akt和Stat3磷酸化水平显著升高,PP2A及其亚基在小鼠心脏再生过程中显著降低。结论新生1 d的小鼠具备完全的心脏再生能力,心尖切除手术会诱导炎症反应增加,IL-6介导的早期炎症促进了新生小鼠心肌细胞的增殖。更多还原

【Abstract】 in mice, neonatal 1 d mice were recruited and divided into two groups: sham operation group and model group. The mice in model group were undergone low temperature anesthesia, then the apex of the heart was removed after thoracotomy; the sham operation group was also performed low temperature anesthesia, thoracotomy and suture process, except the apical resection. Mice was sacrificed at 1 d, 3 d, 7 d and 3 weeks post-surgery respectively, and HE staining was conducted to evaluate the condition of cardiac repair in the two groups. QPCR analysis was used todetect the expression of proliferation related genes and il-6, il-1β and icam1; the expression levels of serum IL-6,TNF-α and IL-1β were checked by ELISA kit; The expression levels of IL-6 downstream targets Akt, Ak(tS473),Stat3, Stat3(T705), and the phosphatase PP2 A were investigated by Western blotting. Data showed that the neonatalheart of model group was completely regenerated 7 days after the operation, the regenerated apex restored complete structure. The cardiomyocyte proliferation related genes were significantly increased in the cardiac regeneration process. The transcriptional levels of il-6, il-1β and icam1 were enhanced in the early course of regeneration. IL-6,TNF-α and IL-1β was drastically incresed, in addition, the phosphorylation levels of IL-6 downstream targets Akt and Stat3 were sharply increased during the process of the cardiac regeneration. PP2 A and its subunit B56α were significantly decreased at 1 d and 3d post-surgery and restored to normal levels at week 3. Taken together, the newborn mice have the ability to regenerate the heart completely. And IL-6-mediated early acute inflammation iscritical in cardiomyocyte proliferation after the cardiac injury.更多还原