肺热普清散对MHV-A59感染小鼠治疗作用及炎症因子的影响  

Effect of Feire Puqing Powder against hepatitis coronavirus MHV-A59 infection and inflammatory factors in mice

作　　者：罗敏怡 徐丽艳 谢和兵 侯海荣 王荣春 何金洋[3] 陈锡强 LUO Minyi;XU Liyan;XIE Hebing;HOU Hairong;WANG Rongchun;HE Jinyang;CHEN Xiqiang(Biology Institute,Qilu University of Technology(Shandong Academy of Sciences),Jinan 250103,China;Tibet Shenhou Pharmaceutical Co.,Ltd.,Xigaze 858300,China;Guangzhou University of Chinese Medicine(Science and Technology Innovation Center),Guangzhou 510410,China)

机构地区：[1]齐鲁工业大学(山东省科学院)生物研究所,山东济南250103 [2]西藏神猴药业有限责任公司,西藏日喀则858300 [3]广州中医药大学科技创新中心,广东广州510410

出　　处：《药物评价研究》2024年第7期1604-1610,共7页Drug Evaluation Research

基　　金：西藏自治区科技厅科技发展项目(XZ202202YD0020C);日喀则市区域科技协同创新专项(QYXTZX-RKZ2023-01)。

摘　　要：目的探讨藏药经典方肺热普清散对小鼠肝炎病毒A59(MHV-A59)感染小鼠模型的影响及其对炎症因子的作用。方法以雄性昆明种小鼠为实验对象,利用MHV-A59滴鼻操作建立小鼠冠状病毒感染模型,设置对照组、模型组、阳性(利巴韦林)组和肺热普清散低、中、高剂量(25、50、100 mg·kg^(-1))3组,每天ig给药1次,连续给药10 d,考察记录造模期内小鼠体质量变化,处死后称体质量并计算小鼠肺脏指数和肝脏指数;使用Elisa试剂盒测定小鼠血清中炎症因子白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)含量;利用实时荧光定量PCR(qRT-PCR)方法检测小鼠肝脏中IL-1β、IL-18的mRNA表达水平和血清中MHV-A59病毒载量;通过苏木素-伊红(HE)染色,检测肺热普清散对肝脏和肺脏细胞坏死及炎症细胞浸润的影响。结果与对照组比较,模型组的体质量增长缓慢(P<0.01);肺热普清散3个剂量组的体质量每日递增,中、高剂量组在第5~8天均与模型组有显著差异(P<0.01);各组小鼠肺脏指数组间无显著性差异,肺热普清散中剂量组肝脏指数与模型组有显著性差异(P<0.05);模型组病毒感染后血清中炎症因子IL-1β和IL-18显著性升高(P<0.001),与模型组比较,肺热普清散3个剂量组均可降低血清中IL-18水平(P<0.001、0.01);模型组肝脏组织中IL-1β和IL-18的mRNA表达水平均显著升高(P<0.001);与模型组比较,肺热普清散高剂量组肝脏中IL-1β转录水平显著降低(P<0.01);与模型组比较,肺热普清散3组实验动物肝脏组织中IL-18水平未出现显著性变化;MHV载量测定结果显示,与模型组比较,利巴韦林组和肺热普清散高剂量组血清中MHV载量显著性降低(P<0.01);病理切片结果显示,模型组肝脏细胞出现广泛坏死和变性,并出现炎症细胞浸润,气球样变等现象,肺热普清散高剂量和利巴韦林组出现点状病灶、炎症细胞浸润等明显减少现象;模型组肺组织肺泡明显间隔增�Objective To explore the effects and inflammatory factors of the Tibetan medicine Feire Puqing Powder(FPP)on the mouse model of hepatitis coronavirus A59(MHV-A59)infection.Methods Male Kunming mice were used as experimental subjects treated with MHV-A59 by nose-dropping,and six groups were set up:the control,the model,the positive(ribavirin),and the FPP's low-,medium-,and high-dosage(25,50,and 100 mg·kg^(-1))groups,and the FPP was ig administered once a day for 10 consecutive days,and the body weight of the mice during the modeling period was examined and recorded,and the lung and liver indices of the mice were examined after execution;The serum levels of IL-1βand IL-18 were determined using the Elisa kit;The mRNA of IL-1βand IL-18 in the liver,and the viral load in the serum were detected using the qRT-PCR;The pathological sections of liver and lung were stained with hematoxylin-eosin(HE),and the necrotic and inflammatory cell infiltration of the liver and lung in each experimental group were observed and recorded under the microscope.Results Compared with the control group,the body weight of the model group increased slowly(P<0.01);The body weight of the three dose groups of FPP increased daily,and there was a significant difference between middle and high dose groups with the model group on days 5-8(P<0.01);There was a significant difference at the liver index of the middle dose group of FPP vs the model group(P<0.05),while others were no significant difference on the lung index of the mice in each group;The serum inflammatory factors IL-1βand IL-18 were significantly elevated(P<0.001),and compared with the model group,all three dose groups of FPP reduced the serum level of IL-18,(P<0.001,0.01);The IL-1βand IL-18 were significantly elevated in liver tissues of the model group(P<0.001);Compared with the model group,the transcript level of IL-1βin the liver treated by FPP high-dose group was significantly reduced(P<0.01);The level of IL-18 in the liver tissues of experimental animals in FPP triple-dose gro

关 键 词：肺热普清散 小鼠肝炎病毒A59 冠状病毒 白细胞介素-1Β 炎症 利巴韦林 

分 类 号：R29[医药卫生—民族医学] R51[医药卫生—中医学] R37