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  

Effects of peiminine B on Streptococcus pneumoniae-induced alveolar epithelial cell injury and its mechanism

作　　者：张睿 李翠红 王有琴 关君艳 ZHANG Rui;LI Cuihong;WANG Youqin;GUAN Junyan(Dept.of Pediatrics,Suizhou Hospital Affiliated to Hubei Medical College(Suizhou Central Hospital),Hubei Suizhou 441300,China;Dept.of Pediatrics,Xiangyang Central Hospital Affiliated to Hubei University of Arts and Sciences,Hubei Xiangyang 441021,China)

机构地区：[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441300 [2]湖北文理学院附属襄阳市中心医院儿科,湖北襄阳441021

出　　处：《中国药房》2025年第7期820-825,共6页China Pharmacy

基　　金：湖北省卫生健康委科研立项项目(No.WJ2019-AB008)。

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HPAEpi C,随机分为对照组(Control组),SP组(1×10^(8) cfu/m L的SP菌液),PEI低、中、高浓度组(1×10^(8) cfu/m L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^(8) cfu/m L的SP菌液+0.20 mmol/L的PEI+10μmol/L的SC79)。除Control组外,其余各组细胞均以SP菌液和(或)相应药液处理。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。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 factorκB(NF-κB)signaling pathway.METHODS Human alveolar epithelial cells(HPAEpiC)were taken and randomly divided into the Control group,SP group(1×10^(8) cfu/mL SP bacterial solution),low-,medium-,and high-concentration PEI groups(1×10^(8) cfu/mL SP bacterial solution+0.05,0.10,0.20 mmol/L PEI),and high-concentration PEI+Akt activator group(P-H+SC79 group,1×10^(8) cfu/mL SP bacterial solution+0.20 mmol/L PEI+10μmol/L SC79).Except for the Control group,the 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 Rac1 and the phosphorylation levels of Akt and NF-κB in the SP group were significantly increased or up-regulated,while SOD content and the protein expression of CDK1 were significantly decreased or down-regulated(P<0.05).Compared with the SP group,the above indexes in PEI groups were significantly improved in a concentration-dependent manner(P<0.05).SC79 could significantly reverse the improvement effect of the high concentration of PEI(P<0.05).CONCLUSIONS PEI can alleviate SP-induced inflammation and oxidative stress damage of alveolar epithelial

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 

分 类 号：R965[医药卫生—药理学]