南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (11): 1662-1667.doi: 10.12122/j.issn.1673-4254.2020.11.20

• • 上一篇    下一篇

电针刺激通过JAK1/STAT3通路减轻脓毒症大鼠的急性肺损伤

谢璨灿，吴双华，李峥嵘，黄 冰，曾维忠
  

  • 出版日期:2020-11-20 发布日期:2020-11-23

Electroacupuncture protects septic rats from acute lung injury through the JAK1/STAT3 pathway

  • Online:2020-11-20 Published:2020-11-23

RichHTML

35

HTML

PDF

631

摘要： 目的 探讨电针对脓毒症大鼠急性肺损伤的影响及作用机制。方法 采用SPF级SD大鼠60 只，用随机数字表法分组。假手术组（SHAM）15 只：只开腹而不结扎盲肠；脓毒组共45 只，采用盲肠结扎穿孔制术（CLP）脓毒症肺损伤模型制备，制备成功后随机分为脓毒症急性肺损伤组（ALI）15 只：不做进一步处理；脓毒症急性肺损伤+电针非穴位组（ALI+SEA）15 只、脓毒症急性肺损伤+电针穴位组（ALI+EA）15 只：针刺双侧内关穴及足三里，电刺激的频率、强度与时间与ALI+SEA组保持一致。于CLP后12 h后处死大鼠，称量大鼠肺组织，测定大鼠肺组织湿/干重比值（W/D），HE 染色检测肺组织病理变化，Tunel染色计算肺组织凋亡细胞比例，酶联免疫吸附试验（ELISA）检测大鼠肺组织中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的浓度，蛋白质免疫印迹试验（Western blot）检测凋亡相关蛋白Bax、Caspase-3表达以及核转录因子JAK1/STAT3信号通路中重要蛋白JAK1、STAT3的表达。结果 ALI与SHAM相比呈现出明显的肺损伤病理表型，表现为肺湿/干重比值增加（P<0.01），血清中TNF-α和IL-6水平显著上升（P<0.01），组织内JAK1、STAT3、Caspase-3、Bax表达水平显著上调（P<0.01）；ALI+SEA与ALI相比以上指标无显著性变化（P>0.05）；ALI+EA与ALI+SEA组比，能显著的减轻脓毒症诱发的肺部病理变化，表现为肺湿/干重比值升高受到抑制（P<0.01），血清中TNF-α和IL-6上升得到缓解（P<0.01），组织中JAK1、STAT3、Caspase-3、Bax的表达升高显著下调（P<0.01）。结论 电针可关联JAK1/STAT3通路的机制，抑制脓毒症大鼠炎性介质的释放及细胞凋亡，减轻脓毒症大鼠的肺损伤。

关键词: 电针, JAK1/STAT3通路, 脓毒症, 急性肺损伤

Abstract: Objective To explore the protective effect of electroacupuncture against acute lung injury (ALI) in septic rats and explore the mechanism. Methods Sixty male SD rats were randomly divided into cecal ligation and puncture (CLP)-induced sepsis group (n=45) and sham operation group (n=15; with laparotomy but without CLP). The rat models of sepsis were randomized into ALI group (n=15) without further treatment, ALI+SEA group (n=15) treated with electroacupuncture at the point far from the Zusanli acupoint for 30 min, and ALI+EA group (n=15) with electroacupuncture at Zusanli with identical frequency, intensity and duration of electrical stimulation. All the rats were sacrificed at 12 h after CLP for measurement of the weight and the wet/dry weight (W/D) ratio of the lungs. Pathological changes of the lung tissues were examined using HE staining, and the contents of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the homogenate of the lung tissues were detected using enzyme-linked immunosorbent assay (ELISA). TUNEL staining was used to detect the apoptotic cells, and the expressions of Bax, caspase-3 and the important proteins in the JAK1/STAT3 signaling pathway (JAK1 and STAT3) were detected with Western blotting. Results Compared with those in the sham operation group, the rats in ALI group showed obvious lung pathologies with significantly increased lung W/D ratio (P<0.01), pulmonary expressions of TNF-α and IL-6 (P<0.01), and obvious up-regulation of JAK1, STAT3, caspase-3, and Bax expressions (P<0.01); similar changes were also observed in ALI+SEA group (P>0.05). Compared with those in ALI+SEA group, the rats in ALI+EA group showed significantly milder lung pathologies, lowered lung W/D ratio (P<0.01) and decreased pulmonary expressions of TNF-α, IL-6, JAK1, STAT3, caspase-3 and Bax (P<0.01). Conclusion Electroacupuncture can inhibit the release of inflammatory mediators and cell apoptosis via the JAK1/STAT3 pathway to reduce lung injuries in septic rats.

Key words: electroacupuncture, JAK1/STAT3 pathway, sepsis, acute lung injury