Page 90 - 《中国药房》2024年9期

葫芦素B预防小鼠脓毒症急性肺损伤的作用及机制 Δ

陈寿珊 ，李方芳，刘福艳，付 超，汤正珍（遵义市第一人民医院儿童重症医学科，贵州 遵义 563000）
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中图分类号 R965 文献标志码 A 文章编号 1001-0408（2024）09-1108-05
DOI 10.6039/j.issn.1001-0408.2024.09.14

摘 要 目的 研究葫芦素B（CB）对脓毒症急性肺损伤（ALI）的预防作用及机制。方法 将小鼠分为对照组、模型组、地塞米松组
（阳性对照，2 mg/kg）和CB低、高剂量组（25、50 mg/kg），各组小鼠腹腔注射相应药物，每天1次，连续3 d。末次给药24 h后，除对
照组小鼠外，其余各组小鼠采用腹腔注射脂多糖（10 mg/kg）的方法构建脓毒症ALI模型（每组8只小鼠纳入实验）。24 h后，检测
小鼠血常规指标（全血中白细胞总数、中性粒细胞数、淋巴细胞数）、肺功能指标（肺总阻力、肺出气阻力、肺动态顺应性、呼气峰值
流速和最大通气量）、肺组织干湿比；检测小鼠肺组织中髓过氧化物酶（MPO）水平和血清中肿瘤坏死因子α（TNF-α）、白细胞介素
1β（IL-1β）、IL-6、超氧化物歧化酶（SOD）、丙二醛（MDA）水平；观察小鼠肺组织病理学形态；免疫组化法检测小鼠肺组织中磷酸化
信号转导及转录活化因子3（p-STAT3）阳性表达情况；Western blot法检测小鼠肺组织IL-6/Janus激酶2（JAK2）/STAT3信号通路相
关蛋白表达水平。结果 与对照组比较，模型组小鼠肺总阻力、肺出气阻力、肺组织干湿比，全血中白细胞总数、中性粒细胞数、淋
巴细胞数，肺组织中MPO水平，血清中MDA、IL-6、IL-1β、TNF-α水平，p-STAT3蛋白光密度值以及IL-6、IL-6受体（IL-6R）蛋白表
达水平和JAK2、STAT3蛋白磷酸化水平均显著升高（P＜0.01）；肺动态顺应性、呼吸峰值流速、最大通气量和血清中SOD水平均显
著降低（P＜0.05或P＜0.01），肺组织出现肺泡塌陷和炎症细胞浸润。与模型组比较，地塞米松组和CB各剂量组小鼠上述指标均
显著逆转（P＜0.05或P＜0.01），肺组织病理损伤减轻。结论 CB可能通过抑制IL-6/JAK2/STAT3信号通路活性，减轻炎症反应，
进而预防小鼠脓毒症ALI。
关键词 葫芦素B；脓毒症；急性肺损伤；IL-6/JAK2/STAT3信号通路；炎症

Effect and mechanism of cucurbitacin B preventing sepsis-induced acute lung injury in mice
CHEN Shoushan，LI Fangfang，LIU Fuyan，FU Chao，TANG Zhengzhen（Dept. of Pediatric Intensive Care
Medicine， the First People’s Hospital of Zunyi， Guizhou Zunyi 563000， China）

ABSTRACT OBJECTIVE To investigate the preventive effect of cucurbitacin B （CB） on sepsis-induced acute lung injury
（ALI） and its mechanism. METHODS The mice were divided into control group， model group， dexamethasone group （positive
control， 2 mg/kg）， CB low-dose and high-dose groups （25， 50 mg/kg）. Each group was given relevant medicine intraperitoneally，
once a day， for 3 consecutive days. Twenty-four hours after the last administration， those groups were given lipopolysaccharide （10
mg/kg） intraperitoneally to establish sepsis-induced ALI model （finally， 8 mice per group were included in the experiment）， except
for control group. Twenty-four hours after medication， blood routine indicators （total white blood cell count， neutrophils count，
lymphocytes count）， lung function indicators （total lung resistance， pulmonary outflow resistance， lung dynamic compliance， peak
expiratory flow rate， and maximum ventilation volume）， dry wet ratio of lung tissue were measured in each group. The lung tissue
level of myeloperoxidase （MPO）， and the serum levels of tumor necrosis factor- α （TNF- α）， interleukin 1β （IL-1β）， IL-6，
superoxide dismutase （SOD） and malondialdehyde （MDA） were all detected. The pathological changes of lung tissue were
observed； immunohistochemistry was used to detect the positive expression of phosphorylation signal transducer and activator of
transcription 3 （p-STAT3） in the lung tissue. Western blot assay was used to detect the expressions of proteins related to IL-6/JAK2/
STAT3 signaling pathway in the lung tissue. RESULTS Compared with control group， total pulmonary resistance， pulmonary flow
resistance， dry wet ratio of lung tissue， the total white blood cell count， neutrophils count， lymphocytes count of whole blood， the
lung tissue level of MPO and serum levels of MDA， IL-6， IL-1β and TNF-α， the p-STAT3 protein optical density value， the
protein expressions of IL-6 and IL-6 receptor， and the phosphorylation levels of JAK2 and STAT3 protein were increased
significantly in the model group （P＜0.01）， while lung dynamic compliance， peak expiratory flow rate， maximum ventilation
volume and serum level of SOD were decreased significantly （P＜0.05 or P＜0.01）. Pulmonary tissue showed alveolar collapse and
infiltration of inflammatory cells. Compared with the model group， the above indexes of mice were reversed significantly in
dexamethasone group and CB groups （P＜0.05 or P＜0.01）， the pathological damage of lung tissue was reduced. CONCLUSIONS
CB can prevent sepsis-induced ALI by inhibiting the activity of
Δ 基金项目 遵义市科技计划项目（No.202252） IL-6/JAK2/STAT3 signaling pathway and relieving
＊第一作者 主治医师。研究方向：重症医学。E-mail：fjuanxui@
inflammatory reactions.
163.com
# 通信作者 主任医师。研究方向：儿童呼吸系统疾病诊断与治 KEYWORDS cucurbitacin B； sepsis； acute lung injury； IL-
疗。E-mail：1608543057@qq.com 6/JAK2/STAT3 signaling pathway； inflammation

· 1108 · China Pharmacy 2024 Vol. 35 No. 9 中国药房 2024年第35卷第9期