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术前雾化吸入盐酸戊乙奎醚对单肺通气时非通气侧肺损伤的影响及作用机制研究
亢旭明,吴霜婷,倪坤强,周俊辉
471009 河南,郑州大学附属洛阳中心医院麻醉科(亢旭明,吴霜婷,倪坤强);450000 郑州,河南省胸科医院,郑州大学附属胸科医院麻醉科(周俊辉)
摘要:
[摘要] 目的 探讨术前雾化吸入盐酸戊乙奎醚在减轻单肺通气(OLV)时非通气侧肺损伤的影响及作用机制。方法 招募2021年3月至2022年5月于郑州大学附属洛阳中心医院择期行胸腔镜下肺癌根治术患者60例,采用随机数字表法将其分为观察组和对照组,每组30例。麻醉诱导后即刻,对照组予雾化吸入异丙托溴铵,观察组予雾化吸入盐酸戊乙奎醚。于全身麻醉诱导后即刻(T0),以及OLV开始后0.5 h(T1)、1 h(T2)、2 h(T3)时检测血氧分压(PaO2)和二氧化碳分压(PaCO2)。术中切取肿瘤周边的正常肺组织标本进行病理学检查,计算肺损伤评分。采用TUNEL法计算细胞凋亡指数(AI)。采用Western blot法检测肺组织细胞凋亡和自噬标志性蛋白的表达水平。结果 光镜下可见对照组肺组织形态、结构发生明显损伤,而观察组肺组织损伤显著减轻。在观察时间内,两组PaO2均呈下降趋势,PaCO2呈上升趋势,且观察组变化幅度较小(P<0.05),在T1~T3时间点与对照组比较差异有统计学意义(P<0.05)。与对照组比较,观察组肺损伤评分、AI、B淋巴细胞瘤-2相关X蛋白(Bax)、微管相关蛋白1轻链3(LC3)-Ⅱ、自噬标志性蛋白Beclin-1水平,以及LC3-Ⅱ/LC3-Ⅰ比值显著降低(P<0.05),而B淋巴细胞瘤-2(Bcl-2)、LC3-Ⅰ蛋白水平以及Bcl-2/Bax比值均显著升高(P<0.05)。结论 术前雾化吸入盐酸戊乙奎醚可减轻OLV时的非通气侧肺损伤,而肺组织细胞凋亡及自噬的抑制在其中具有重要作用。
关键词:  单肺通气  盐酸戊乙奎醚  雾化吸入  肺损伤  细胞凋亡  自噬
DOI:10.3969/j.issn.1674-3806.2023.08.09
分类号:R 614
基金项目:河南省医学科技攻关项目联合共建项目(编号:2018020564)
A study on the effect of preoperative aerosol inhalation of penehyclidine hydrochloride on non-ventilated lung injury during one-lung ventilation and its mechanisms of action
KANG Xu-ming, WU Shuang-ting, NI Kun-qiang, et al.
Department of Anesthesiology, Luoyang Central Hospital Affiliated to Zhengzhou University, Henan 471009, China
Abstract:
[Abstract] Objective To investigate the effect of preoperative aerosol inhalation of penehyclidine hydrochloride on alleviating non-ventilated lung injury during one-lung ventilation(OLV) and its mechanisms of action. Methods Sixty patients who underwent the elective operation of thoracoscopic radical resection for lung cancer in Luoyang Central Hospital Affiliated to Zhengzhou University from March 2021 to May 2022 were recruited and divided into observation group and control group by random number table method, with 30 cases in each group. Immediately after induction of anesthesia, the patients in the control group inhaled ipratropium bromide by aerosol inhalation, and the patients in the observation group inhaled penehyclidine hydrochloride by aerosol inhalation. Partial pressure of arterial oxygen(PaO2) and partial pressure of arterial carbon dioxide(PaCO2) were measured immediately after induction of general anesthesia(T0), and 0.5 hours(T1), 1 hour(T2) and 2 hours(T3) after OLV. During the operation, the normal lung tissue specimens around the tumor were excised for pathological examination and lung injury scores were calculated. Apoptosis index(AI) was calculated by terminal-deoxynucleotide transferase mediated nick end labeling(TUNEL) method. The expression levels of apoptosis and autophagy marker protein in the lung tissues were detected by Western blot. Results The morphology and structure of the lung tissues in the control group were obviously damaged under light microscope, while the damage of the lung tissues in the observation group was significantly reduced. During the observation period, PaO2 showed a decreasing trend and PaCO2 showed an increasing trend in both groups, and the change range of the observation group was smaller(P<0.05), and the differences between the two groups were statistically significant at the time points of T1 -T3(P<0.05). Compared with those in the control group, the lung injury scores, AI, B-lymphocytoma-2 related X protein(Bax), microtubule-associated protein 1 light chain 3(LC3)-Ⅱ, the level of autophagy marker protein Beclin-1 and the ratio of LC3-Ⅱ/LC3-Ⅰin the observation group were significantly decreased(P<0.05), while the levels of B-lymphocytoma-2(Bcl-2) and LC3-Ⅰ protein and the ratio of Bcl-2/Bax were significantly increased(P<0.05). Conclusion Preoperative aerosol inhalation of penehyclidine hydrochloride can alleviate the non-ventilated lung injury during OLV, and the inhibitions of lung tissue apoptosis and autophagy play important roles.
Key words:  One-lung ventilation  Penehyclidine hydrochloride  Aerosol inhalation  Lung injury  Apoptosis  Autophagy