论文部分内容阅读
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。
Objective To explore the role of IL-6-mediated early inflammation in cardiac regeneration in newborn mice and its mechanism. Methods Newborn 1-day-old mice were randomly divided into model group and sham-operated group. The former received hypothermic anesthesia to excise the apex and the latter was only used for thoracotomy. The hearts were harvested at 1, 3, 7 and 21 days after surgery. The paraffin sections were stained with H & E and qPCR to detect the expression of proliferation-related genes. The transcriptional levels of IL-6, IL-1β and icam1 were detected. The levels of IL-6, TNF-α and IL-1βwere detected by ELISA. The expressions of Akt, Akt (S473), Stat3 and Stat3 (T705) Changes in negative regulation gene PP2A. Results At 7 days after operation, the mice in model group basically completed the process of cardiac regeneration. Slice staining showed that the apical structure of regenerated heart was intact and the expression of genes related to proliferation of cardiomyocytes increased. The inflammatory factors such as IL-6, TNF-α and IL-1β increased sharply in the early postoperative period, the phosphorylation levels of Akt and Stat3 in the downstream substrates were significantly increased, while the PP2A and its subunits were significantly decreased in the cardiac regeneration of mice . Conclusion Newborn 1-day-old mice have complete cardiopulmonary regeneration. Apical excision can induce an increase in inflammatory response. Early inflammation mediated by IL-6 promotes cardiomyocyte proliferation in neonatal mice.