摘要
目的明确转化生长因子-β1(transforming growth factor-β1,TGF-β1)在机械通气促进肺组织有氧酵解并加速肺纤维化过程中的作用。方法将24只C57BL/6小鼠按照随机数字表法分为假手术组(Sham组)、溶剂对照组(Vehicle组)、机械通气组(MV组)和TGF-β1受体抑制剂+机械通气组(TGFβ-Ri+MV组),每组6只。其中Sham组仅做麻醉后插管处理并保持自主呼吸,Vehicle组使用阴性对照溶剂灌胃5 d后进行麻醉插管处理并保持自主呼吸,MV组采用潮气量20 ml/kg、通气频率70次/min单次机械通气2 h,TGFβ-Ri+MV组使用TGF-β1受体抑制剂SB525334以10 mg/kg剂量灌胃5 d后采用潮气量20 ml/kg、通气频率70次/min单次机械通气2 h,以上各组7 d后取材。采用ELISA法检测肺泡灌洗液中TGF-β1含量,Western blot法检测肺组织乳酸脱氢酶A(lactate dehydrogenase A,LDHA)、Ⅰ型胶原蛋白α1链(collagen type Ⅰ α1 chain,COL1A1)蛋白含量,比色法检测肺泡灌洗液中乳酸含量,Masson染色观察肺组织纤维化程度。结果与Sham组比较,MV组TGF-β1含量(t=2.07,P=0.047)、LDHA蛋白(t=5.09,P=0.003)、乳酸含量(t=2.42,P=0.046)、COL1A1蛋白含量(t=4.327,P=0.012)升高,Masson染色显示肺组织胶原沉积增多。与MV组比较,TGFβ-Ri+MV组LDHA蛋白(t=2.43,P=0.038)、乳酸含量(t=3.16,P=0.025)、COL1A1蛋白含量(t=5.78,P=0.004)下降,Masson染色显示肺组织胶原沉积减少。结论机械通气可以引起肺组织TGF-β1生成并促进有氧酵解,从而加速机械通气相关性肺纤维化进程。
Objective To clarify the role of transforming growth factor-β1(TGF-β1)in mechanical ventilation to promote aerobic glycolysis and accelerate the process of pulmonary fibrosis.Methods According to the random number table method,a total of 24 C57BL/6 mice were divided into the following groups(n=6):a sham operation group(Sham group),a vehicle control group(Vehicle group),a mechanical ventilation group(MV group)and a TGF-β1 receptor inhibitor+mechanical ventilation(TGFβ-Ri+MV)group.The Sham group only underwent intubation after anesthesia and maintained spontaneous breathing,while the Vehicle group was subjected to anesthesia intubation after intragastric administration of negative control vehicle for 5 days and maintained spontaneous breathing.The MV group underwent single mechanical ventilation with a tidal volume of 20 ml/kg and a ventilation frequency of 70 breaths per minute for 2 h.The TGFβ-Ri+MV group was intragastrically administered with 10 mg/kg SB525334,a TGF-β1 receptor inhibitor for 5 days,before single mechanical ventilation with a tidal volume of 20 ml/kg and a ventilation frequency of 70 breaths per minute for 2 h.Samples of each group were collected 7 days later.The content of TGF-β1 in alveolar lavage fluid was detected by enzyme-linked immunosorbent assay(ELISA).The amounts of lactate dehydrogenase A(LDHA)and collagen type Ⅰ α1 chain(COL1A1)protein in lung tissue were detected by Western blot.The content of lactic acid in alveolar lavage fluid was detected by colorimetry.The degree of pulmonary fibrosis was observed by Masson staining..Results Compared with the Sham group,the MV group presented increases in the content of TGF-β1(t=2.07,P=0.047),in the amounts of LDHA(t=5.09,P=0.003)and lactic acid(t=2.42,P=0.046),and in the content of COL1A1 protein(t=4.327,P=0.012),with increased collagen deposition by Masson staining.Compared with the MV group,the TGFβ-Ri+MV group presented decreases in the amounts of LDHA(t=2.43,P=0.038)and lactic acid(t=3.16,P=0.025)and in the content of COL1A1 protein(t=5.78,P=0.004),with decreased collagen deposition by Masson staining.Conclusion Mechanical ventilation can induce the production of TGF-β1 in lung tissue and promote aerobic glycolysis,which can accelerate the process of mechanical ventilation-associated pulmonary fibrosis.
作者
胡钺
梅舒雅
徐侨翌
皋源
何征宇
邢顺鹏
Hu Yue;Mei Shuya;Xu Qiaoyi;Gao Yuan;He Zhengyu;Xing Shunpeng(Department of Critical Care Medicine,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China)
出处
《国际麻醉学与复苏杂志》
CAS
2022年第1期1-5,共5页
International Journal of Anesthesiology and Resuscitation
基金
国家自然科学基金(81870052)
上海市仁济医院临床科研培育基金(PY2018-ⅡA-01)
上海人才发展资金(2020078)。
