摘要
目的 观察富氢液对心肌缺血/再灌注大鼠急性肺损伤的预防作用,并探讨其相关作用机制。方法 成年雄性SD大鼠随机分为心肌缺血/再灌注+富氢液+HO-1抑制剂组(抑制剂组)、心肌缺血/再灌注+富氢液组(HS组)、心肌缺血/再灌注组(I/R组)、假手术组(S组)。采用冠脉结扎术制备心肌缺血/再灌注急性肺损伤模型。抑制剂组大鼠在冠脉结扎术前30 min腹腔注射锌原卟啉(ZnPPIX,25 mg/kg),于再灌注前5 min腹腔注射富氢液10 mL/kg。HS组大鼠于再灌注前5 min腹腔注射富氢液10 mL/kg。I/R组大鼠分离左冠状动脉前降支并结扎30 min后,松开结扎线再灌注120 min。S组大鼠仅穿线不结扎。再灌注2 h时,检测各组大鼠支气管肺泡灌洗液(BALF)总蛋白,采用ELISA法检测各组大鼠血清和肺组织肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、白细胞介素10(IL-10)及肺组织血红素氧合酶-1(HO-1)。再灌注2 h时,取各组大鼠组织测肺湿/干重比;采用HE染色观察各组大鼠肺组织损伤程度并评分;采用Western blotting法检测各组大鼠肺组织HO-1。结果 与S组相比,I/R组、HS组、抑制剂组大鼠BALF总蛋白含量、肺W/D和肺组织病理评分均高(P均<0.05);血清和肺组织TNF-α、IL-1β和IL-10水平均高(P均<0.05);肺组织HO-1蛋白浓度和水平均高(P均<0.05)。与I/R组相比,HS组大鼠BALF总蛋白含量、肺W/D和肺组织病理评分均低,血清和肺组织TNF-α、IL-1β水平均低,IL-10水平高(P均<0.05);肺组织HO-1蛋白浓度和水平均高(P均<0.05)。与HS组相比,抑制剂组大鼠BALF总蛋白含量、肺W/D和肺组织病理评分均高(P均<0.05);血清和肺组织TNF-α、IL-1β水平均高,IL-10水平低(P均<0.05);肺组织HO-1蛋白浓度和水平低(P均<0.05)。结论 富氢液可减轻心肌缺血/再灌注大鼠急性肺损伤,其机制可能与上调HO-1从而抑制肺组织炎性反应有关。
Objective lung injury in rats induced by myocardial ischemia/reperfusion(I/R)and its mechanism.Methods rates were randomly divided into four groups:I/R+hydrogen-rich fluid+HO-1 inhibitor group(inhibitor group),myocardial I/R+hydrogen-rich fluid group(HS group),I/R group,and sham operation group(S group). The rat model of acute lung injury induced by myocardial I/R was established by ligation of coronary artery. Rats in the inhibitor group were treated with intraperitoneal injection of zinc-protoporphyrin IX(ZnPPIX,25 mg/kg)at 30 min before operation. Rats in the inhibitor group and HS group were injected intraperitoneally with hydrogen-rich fluid(10 mL/kg)at 5 min before reperfusion,respectively. For rats in the I/R group,we successively separated and ligated the left anterior descending coronary arteries for 30 min and loosened them for 120 min. Rats in the S group underwent thoracotomy without artery ligation. At 2 h after myocardial reperfusion,the bronchoalveolar lavage fluid was obtained to detect the total protein concentration;serum and lung tissues were collected to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-10(IL-10)and heme oxygenase-1(HO-1)by enzyme-linked immune sorbent assay(ELISA);wet/dry(W/D)of lung tissues was tested;the histopathologic changes were observed by htoxylin-eosin(HE)staining,and lung injury score was assessed;the expression of HO-1 of lung tissues was detected by Western blotting.Results group,the total protein concentration in BALF,W/D of lung tissues and the lung injury score,the levels of TNF-α,IL-1β,and IL-10 in the serum and lung tissues,and the level and the concentration of HO-1 protein in the lung tissues were higher in the I/R group,HS group,and inhibitor group(all P<0. 05). Compared with the I/R group,the total protein concentration in BALF,W/D of lung tissues and the lung injury score were significantly lower(all P<0. 05);the levels of TNF-α and IL-1β in the serum and lung tissues were lower but the level of IL-10 was higher;the level and the concentration of HO-1 protein in the lung tissues were higher in the HS group(all P<0. 05). Compared with the HS group,the total protein concentration in BALF,W/D of lung tissues and the lung injury score were significantly higher(all P<0. 05);the levels of TNF-α and IL-1β were higher but the level of IL-10 was lower(all P<0. 05);the level and the concentration of HO-1 protein in the lung tissues were lower in the inhibitor group(both P<0. 05).Conclusion can obviously alleviate acute lung injury in rats induced by myocardial I/R through up-regulating HO-1 to suppress the inflammation of lung tissues.
作者
王树志
李丽华
付乃宽
WANG Shuzhi;LI Lihua;FU Naikuan(Cardiac Function Department,Tianjin Thoracic Hospital,Tianjin Institute of Cardiovascular Diseases,Tianjin 300222,China)
出处
《山东医药》
CAS
2022年第3期6-9,共4页
Shandong Medical Journal
关键词
氢
心肌缺血再灌注损伤
急性肺损伤
血红素氧合酶
hydrogen
mocardial ischemia reperfusion injury
acute lung injury
heme oxygenase
