Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, Fuzhou, 350001, Fujian Province, People's Republic of China.
Anesthesiology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350004, Fujian Province, People's Republic of China.
J Cardiothorac Surg. 2021 May 10;16(1):127. doi: 10.1186/s13019-021-01471-5.
This study aimed to explore whether the mechanical stretching-induced expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in pulmonary veins occurred through the stretch-activated channel (SAC)/ mitogen-activated protein kinases (MAPKs) pathway.
Sixty male Sprague-Dawley rats were divided into three sham groups and seven model groups. A metal clip was placed on the ascending aorta in the model group to establish PH-LHD rat model. The sham group received a similar operation without ascending aorta clamped. On day 25, pulmonary vein was given mechanical stretching with 0 g, 2.0 g tension in two model groups and two sham groups. Another four model groups were given 2.0 g tension after MAPKs pathway inhibitors soaked. The last sham group and model group rats' pulmonary veins, pulmonary artery and lung tissues were obtained on day 35. Pulmonary vein, pulmonary artery and lung tissue were evaluated by echocardiography, HE staining, immunohistochemistry and western blotting respectively.
On day 25, left heart weight, right ventricular pressure (35.339 cmHO) and left atrial pressure (13.657 cmHO) were increased in model group than those in sham group. Echocardiography showed left heart failure in the PH-LHD group (Interventrieular septum dimension 1.716 mm, left ventricular internal end diastolic dimension 4.888 mm, left ventricular posterior wall thickness in diastole 1.749 mm, ejection fraction 76.917%). But there was no difference in lung tissue between the sham group and PH-LHD group as showed by HE staining. Our results showed that the expression of IL-6 and TNF-α was highly expressed in PH-LHD rats' serum and pulmonary vein, which were further increased after 2.0 g tension was given and were decreased after SAC/MAPKs inhibitors treatment. Meanwhile, on day 25, immunohistochemistry analysis showed the expression of IL-6 and TNF-α was higher in the PH-LHD rats' pulmonary vein than that in pulmonary artery and lung tissue, and these expressions in pulmonary vein of PH-LHD group were also higher than that in sham group. However, on day 35, IL-6 and TNF-α were all increased in the pulmonary veins, arteries and lung tissues. Besides, our results uncovered that SAC/MAPKs pathway were upregulating in PH-LHD rats' pulmonary vein.
In conclusion, pulmonary vein mechanical stretching exacerbated PH-LHD possibly through the SAC/MAPKs pathway and upregulating expression of IL-6 and TNF-α.
本研究旨在探讨肺静脉内白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）的机械拉伸诱导表达是否通过牵张激活通道（SAC）/丝裂原活化蛋白激酶（MAPKs）通路发生。
60 只雄性 Sprague-Dawley 大鼠分为三组假手术组和七组模型组。在模型组中，在升主动脉上放置金属夹以建立 PH-LHD 大鼠模型。假手术组接受类似的手术，但不夹升主动脉。在第 25 天，两组模型组和两组假手术组分别给予 0 g 和 2.0 g 张力对肺静脉进行机械拉伸。另外四个模型组在给予 MAPKs 通路抑制剂浸泡后给予 2.0 g 张力。第 35 天，获取最后一组假手术组和模型组大鼠的肺静脉、肺动脉和肺组织。分别通过超声心动图、HE 染色、免疫组织化学和 Western blot 评估肺静脉、肺动脉和肺组织。
第 25 天，模型组左心重量、右心室压（35.339 cmHO）和左心房压（13.657 cmHO）均高于假手术组。超声心动图显示 PH-LHD 组左心衰竭（室间隔厚度 1.716 mm，左心室舒张末期内径 4.888 mm，左心室后壁舒张期厚度 1.749 mm，射血分数 76.917%）。但 HE 染色显示，假手术组和 PH-LHD 组的肺组织无差异。我们的结果表明，PH-LHD 大鼠血清和肺静脉中 IL-6 和 TNF-α 的表达高度表达，在给予 2.0 g 张力后进一步增加，并在 SAC/MAPKs 抑制剂治疗后减少。同时，在第 25 天，免疫组织化学分析显示 PH-LHD 大鼠肺静脉中 IL-6 和 TNF-α 的表达高于肺动脉和肺组织，PH-LHD 组肺静脉中的表达也高于假手术组。然而，第 35 天，肺静脉、肺动脉和肺组织中均增加了 IL-6 和 TNF-α。此外，我们的结果表明，SAC/MAPKs 通路在 PH-LHD 大鼠肺静脉中上调。
总之，肺静脉机械拉伸通过 SAC/MAPKs 通路加重 PH-LHD，并上调 IL-6 和 TNF-α的表达。
