基于血液中炎症因子网络评价地黄的抗热射病作用  

The evaluation of the anti-heat stroke effect of Rehmannia glutinosa based on the inflammatory factor network

作　　者：冀欣业 马绍壮 张晏源 王晓琴 张波 JI Xinye;MA Shaozhuang;ZHANG Yanyuan;WANG Xiaoqin;ZHANG Bo(School of Pharmacy/Key Laboratory of Xinjiang Endemic Phytomedicine Resources,Ministry of Education,Shihezi University,Shihezi,Xinjiang 832003,China;School of Pharmacy/Sichuan Antimicrobial Industry Research Institute,Chengdu University,Chengdu,Sichuan 610106,China)

机构地区：[1]石河子大学药学院/新疆植物药资源利用教育部重点实验室,新疆石河子832003 [2]成都大学药学院/四川抗菌素工业研究所,四川成都610106

出　　处：《石河子大学学报（自然科学版）》2024年第5期644-651,共8页Journal of Shihezi University(Natural Science)

基　　金：国家自然科学基金项目(U1603122);四川省天府峨眉创新领军人才资助项目(1811)。

摘　　要：目的热射病(HS)是高温高湿环境引起急性热损伤的一种复杂疾病,其发生发展与血液中多种炎症因子密切相关,清热凉血药地黄潜在抗热射病作用尚不明确。方法中国知网、PubMed跨库检索“热射病,Heat stroke”文献,在统计学指导下人工挖掘HS显著性变化的血液炎症因子标志物并构建无标网络(Scale-free-network);收集地黄的活性成分,预测相关靶点并将其与热射病血液炎症因子网络进行关联分析;人工气候箱制作热射病小鼠模型:温度41℃±0.5℃,相对湿度60%±5%,评价地黄粗提物抗HS药效,qRT-PCR方法检测组织中相关炎症因子,分子对接进行药-靶关联验证。结果地黄与热射病之间的相关生物学过程和通路主要集中在炎症反应和凋亡反应。生物学验证结果显示,地黄能够延长热射病小鼠的生存时间,提高小鼠的生存率,减轻肝肾肿胀等急性反应,显著改善肝脏和肾脏的损伤(P<0.05)。qRT-PCR结果显示地黄粗提物能够显著降低炎症因子IL-6、IL-1β、IL-17A、NF-κB、TNF-α的mRNA的表达水平(P<0.05),发挥抗炎作用,这些因子在热射病血液炎症因子网络中占据重要地位。分子对接结果显示活性成分与关键蛋白具有良好的结合活性。结论地黄具有抗热射病的药理活性,作用于热射病血液中炎症因子网络的中心区域,可以改善热射病引起的小鼠肝脏和肾脏损伤、抑制炎症反应。Objective Heat stroke(HS)is a complex disease caused by acute heat injury in high-temperature and high-humidity environments.Its occurrence and development are closely related to a variety of inflammatory factors in the blood.The therapeutical effects of heat-clearing and blood-cooling medicine Rehmannia glutinosa(RG)for heat stroke is still unclear.Methods The literature on'heat stroke'was retrieved from CNKI and Pubmed.Under the guidance of statistics,the markers of blood inflammatory factors with significant changes in HS were manually excavated and a scale-free network was constructed.The RG’s active components were collected,and the related targets were predicted and correlated with the heat stroke blood inflammatory factor network.The heat stroke mouse model in the environment of temperature(41±0.5)℃and relative humidity 60%±5%was made in the artificial climate chamber to evaluate the anti-HS efficacy of the crude extract of RG.The related inflammatory factors in the tissues were detected by qRT-PCR,and the drug-target association was verified by molecular docking.Results The related biological processes and pathways between RG and heat stroke are mainly concentrated in an inflammatory response and apoptotic response.The results of biological verification showed that RG could prolong the survival time of heat stroke mice,improve the survival rate of mice,reduce acute reactions such as liver and kidney swelling,and significantly improve liver and kidney damage(P<0.05).The results of qRT-PCR showed that the crude extract of RG could significantly reduce the mRNA expression levels of inflammatory factors IL-6,IL-1β,IL-17 A,NF-κB and TNF-α(p<0.05),and play an anti-inflammatory role.These factors play an important role in the network of blood inflammatory factors in heat stroke.Molecular docking results showed that the active components had good binding activity with key proteins.Conclusion RG exerts its anti-heatstroke pharmacological effect by inhibiting inflammatory responses and improving liver and

关 键 词：热射病 炎症因子网络 地黄 分子对接 

分 类 号：R961.1[医药卫生—药理学]