表热清防治新冠肺炎合并细菌感染的作用机制  

Mechanism of Biaoreqing in prevention and treatment of SARS-COVID-2 pneumonia with bacterial infection

作　　者：熊静悦[1] 罗红艳 迭磊 覃思光 赵丰娟 谭婉莹 杜仕静 谭正怀[1] XIONG Jingyue;LUO Hongyan;DIE Lei;QIN Siguang;ZHAO Fengjuan;TAN Wanying;DU Shijing;TAN Zhenghuai(Sichuan Academy of Chinese Medicine Science,Chengdu,Sichuan,610041 P.R.China;Yunnan Leiyunshang Lixiang Pharmaceutical Co.,Ltd.,Kunming,Yunnan,650500 P.R.China;Chengdu University of TCM,Chengdu,Sichuan,611130 P.R.China;Southwest Medical University,Luzhou,Sichuan,646000 P.R.China)

机构地区：[1]四川省中医药科学院,四川成都610041 [2]云南雷允上理想药业有限公司,云南昆明650500 [3]成都中医药大学,四川成都611130 [4]西南医科大学,四川泸州646000

出　　处：《华西药学杂志》2024年第6期675-680,共6页West China Journal of Pharmaceutical Sciences

基　　金：四川省中医药管理局重大科技项目(2021XYCZ002);四川省科学技术厅2021年度基本科研业务(2021JDKY0013)。

摘　　要：目的探索傣药表热清防治新冠肺炎合并细菌感染的作用机制。方法采用SARS-COV-2刺突蛋白(SP)10μg·kg^(-1)联合脂多糖(LPS)9 mg·kg^(-1)气管滴注模拟新冠肺炎合并细菌感染致大鼠急性肺损伤,腹腔注射SP+LPS(10μg·kg^(-1)+50μg·kg^(-1))模拟全身中、重度新冠肺炎合并细菌感染致大鼠发热;用乙酸致小鼠腹腔通透性增加,角叉菜胶致小鼠血栓形成以及热板致小鼠疼痛实验,考察表热清对急性肺损伤、发热、炎症、血栓形成的防治及其镇痛作用。结果大鼠气管滴注SP+LPS后,其肺脏指数显著增加,血清总超氧化物歧化酶(SOD)的活性显著降低,丙二醛(MDA)的水平显著增加,肺组织炎细胞浸润明显,肺泡间隔显著增宽。表热清能显著降低SP+LPS致大鼠新冠肺炎模型的肺指数,改善其病理组织学炎症反应、降低其血清MDA、肺组织肿瘤坏死因子-α(TNF-α)及白介素-6(IL-6)的含量。表热清还可显著抑制SP+LPS诱导大鼠体温升高,并可抑制乙酸致小鼠腹腔通透性增高,抑制角叉菜胶诱导小鼠血栓形成。结论表热清能有效改善SP+LPS感染所致肺损伤,作用机制与抑制肺组织TNF-α及IL-6的表达、减少氧化应激反应产物、减轻炎症反应及血栓形成等有关。OBJECTIVE To explore the mechanism of Biaoreqing in prevention and treatment of SARS-CoV-2 pneumonia with bacterial infection.METHODS The SARS-CoV-2 spike protein(SP)combined with lipopolysaccharide(LPS)(10μg·kg^(-1)+9 mg·kg^(-1))was used to induce coronavirus pneumonia with bacterial infection in rats.Peritoneal injection of SP combined with LPS(10μg·kg^(-1)+50μg·kg^(-1))were carried out to induce fever in rats.The anti-inflammatory effect was evaluated by glacial acetic acid induced peritoneal permeability method.The anti-thrombotic effect was evaluated by carrageenan induced thrombosis method.The analgesic activity was evaluated by hot plate method.RESULTS After SP and LPS intratracheal instillation,the pulmonary index and serum MDA level increased significantly in the model group,the activity of serum SOD decreased significantly,the infiltration of inflammatory cells in lung tissues were obvious and the alveolar interval was widened.Biaoreqing reduced the pulmonary index,the serum MDA level and the level of TNF-αas well as IL-6 in lung tissues of model rats.After intraperitoneal injection of SP and LPS,Biaoreqing inhibited the rise of body temperature.Biaoreqing inhibited increased peritoneal permeability induced by glacial acetic acid,and moreover,Biaoreqing inhibited carrageene induced thrombosis in mice.CONCLUSION Biaoreqing can effectively relieve symptoms of lung injury and fever caused by SARS-CoV-2 SP with LPS infection,and inhibit inflammation and thrombosis.The mechanism may be related to the inhibition of TNF-α,IL-6 expression and serum MDA generation,as well as thrombus formation.

关 键 词：表热清 傣药 新冠肺炎合并细菌感染 刺突蛋白 脂多糖 肺损伤 细胞因子 大鼠 

分 类 号：R96[医药卫生—药理学]