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贝母素乙对肺炎链球菌诱导肺泡上皮细胞损伤的影响及机制
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张 睿 ,李翠红 ,王有琴 ,关君艳 [1. 湖北医药学院附属随州医院(随州市中心医院)儿科,湖北 随州
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441300;2.湖北文理学院附属襄阳市中心医院儿科,湖北 襄阳 441021]
中图分类号 R965 文献标志码 A 文章编号 1001-0408(2025)07-0820-06
DOI 10.6039/j.issn.1001-0408.2025.07.09
摘 要 目的 探究贝母素乙(PEI)调节伏隔核Ras相关的C3肉毒素底物1(Rac1)/蛋白激酶B(Akt)/核因子κB(NF-κB)信号通路
对肺炎链球菌(SP)诱导肺泡上皮细胞损伤的影响。方法 取人肺泡上皮细胞HPAEpiC,随机分为对照组(Control组),SP组(1×
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10 cfu/mL的SP菌液),PEI低、中、高浓度组(1×10 cfu/mL的SP菌液+0.05、0.10、0.20 mmol/L的PEI)和PEI高浓度+Akt通路激活
剂组(1×10 cfu/mL的SP菌液+0.20 mmol/L的PEI+10 μmol/L的SC79)。除Control组外,其余各组细胞均以SP菌液和(或)相应
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药液处理。24 h后,检测各组细胞上清液中炎症因子(白细胞介素6、18、1β)水平、细胞氧化应激指标[乳酸脱氢酶(LDH)、超氧化
物歧化酶(SOD)、活性氧(ROS)]含量、凋亡率和增殖/凋亡相关蛋白[周期蛋白依赖性激酶1(CDK1)、B细胞淋巴瘤2相关X蛋白
(Bax)]、通路相关蛋白(Rac1、Akt及磷酸化Akt、NF-κB及磷酸化NF-κB)的表达情况。结果 与Control组比较,SP组细胞上清液
中炎症因子水平,LDH、ROS含量,凋亡率,Bax、Rac1蛋白的表达和Akt、NF-κB蛋白的磷酸化水平均显著升高或上调,SOD含量、
CDK1蛋白的表达均显著降低或下调(P<0.05)。与SP组比较,PEI各浓度组上述指标均显著改善,且呈浓度依赖性(P<0.05);而
SC79可显著逆转高浓度PEI的改善作用(P<0.05)。结论 PEI可以减轻SP诱导的肺泡上皮细胞炎症和氧化应激损伤,抑制细胞
凋亡,上述作用可能是通过抑制Rac1/Akt/NF-κB信号通路而实现的。
关键词 贝母素乙;肺炎链球菌;肺泡上皮细胞;Rac1/Akt/NF-κB信号通路
Effects of peiminine B on Streptococcus pneumoniae-induced alveolar epithelial cell injury and its
mechanism
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ZHANG Rui ,LI Cuihong ,WANG Youqin ,GUAN Junyan [1. Dept. of Pediatrics, Suizhou Hospital Affiliated
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to Hubei Medical College (Suizhou Central Hospital), Hubei Suizhou 441300, China;2. Dept. of Pediatrics,
Xiangyang Central Hospital Affiliated to Hubei University of Arts and Sciences, Hubei Xiangyang 441021,
China]
ABSTRACT OBJECTIVE To investigate the effects of peiminine B (PEI) on Streptococcus pneumoniae (SP)-induced alveolar
epithelial cell injury by regulating the Ras-related C3 botulinum toxin substrate 1 in nucleus accumbens (Rac1)/protein kinase B
(Akt)/nuclear factor κB (NF- κB) signaling pathway. METHODS Human alveolar epithelial cells (HPAEpiC) were taken and
randomly divided into the Control group, SP group (1×10 cfu/mL SP bacterial solution), low-, medium-, and high-concentration
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PEI groups (1×10 cfu/mL SP bacterial solution+0.05, 0.10, 0.20 mmol/L PEI), and high-concentration PEI+Akt activator group
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(P-H+SC79 group, 1×10 cfu/mL SP bacterial solution+0.20 mmol/L PEI+10 μmol/L SC79). Except for the Control group, the
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other groups of cells were treated with SP bacterial solution and/or corresponding drug solution. After 24 h of treatment, the levels
of inflammatory factors (interleukin-6, -18, -1β) in the supernatant solution, the contents of oxidative stress indexes [lactate
dehydrogenase (LDH), reactive oxygen species (ROS) and superoxide dismutase (SOD)], apoptosis rate, as well as the
expressions of proliferation/apoptosis-related proteins [cyclin-dependent kinase 1 (CDK1), B cell lymphoma-2 related X protein
(Bax)] and pathway-related proteins (Rac1, Akt, phosphorylated Akt, NF-κB and phosphorylated NF-κB) were detected in each
group. RESULTS Compared with the Control group, the levels of inflammatory factors in supernatant solution, LDH and ROS
contents, apoptosis rate, the protein expressions of Bax and
Δ 基金项目 湖 北 省 卫 生 健 康 委 科 研 立 项 项 目(No. WJ2019- Rac1 and the phosphorylation levels of Akt and NF-κB in the
AB008) SP group were significantly increased or up-regulated, while
*第一作者 主治医师,硕士。研究方向:儿科呼吸疾病的基础与
SOD content and the protein expression of CDK1 were
临床。E-mail:ziguym@163.com
# 通信作者 副主任医师,硕士。研究方向:儿科呼吸疾病的基础 significantly decreased or down-regulated (P<0.05).
与临床。E-mail:xwqdc83@163.com Compared with the SP group, the above indexes in PEI groups
· 820 · China Pharmacy 2025 Vol. 36 No. 7 中国药房 2025年第36卷第7期