摘要
目的:研究葛根汤颗粒对人冠状病毒229E(hCoV-229E)寒湿疫毒袭肺证病证结合肺炎小鼠的治疗作用。方法:BALB/c小鼠分为正常组、感染组、寒湿组、模型组、磷酸氯喹组(0.18 g·kg^(-1))、干扰素α2b(IFN-α2b)组(1.83×10^(6)U·kg^(-1))及葛根汤颗粒高、低剂量组(6.6、3.3 g·kg^(-1)),每组10只,采用寒湿环境加hCoV-229E感染进行造模并给药。观察小鼠一般状态及肺指数,使用实时荧光定量聚合酶链式反应(Real-time PCR)检测肺组织病毒载量,用苏木素-伊红(HE)染色法评价肺组织病变,运用酶联免疫吸附测定法(ELISA)检测血清胃肠激素、肺组织炎性因子的水平,利用流式细胞术检测外周血淋巴细胞百分比。结果:葛根汤颗粒能够明显缓解模型小鼠精神萎靡、四肢无力、大便黏腻等状态;葛根汤颗粒高剂量组能够明显降低模型小鼠的肺指数、组织病理学评分、血清胃动素水平(P<0.05,P<0.01);与模型组比较,葛根汤颗粒高、低剂量组均可明显升高血清胃泌素水平(P<0.05,P<0.01),明显升高外周血CD4^(+)、CD8^(+)T淋巴细胞百分比(P<0.05,P<0.01),显著降低肺组织中肿瘤坏死因子-α(TNF-α)水平(P<0.01),并使白细胞介素-6(IL-6)水平呈现降低趋势。结论:葛根汤颗粒能够改善hCoV-229E寒湿疫毒袭肺证病证结合小鼠的一般体征,调节胃肠激素水平,降低肺指数和肺组织病理学评分,并可能通过抑制肺组织中炎性细胞因子、恢复外周血淋巴细胞百分比发挥免疫调节作用,从而对模型小鼠起到治疗作用。
Objective:To determine the therapeutic effect of Gegentang granules on a disease-syndrome mouse model combining human coronavirus 229E(hCoV-229E)pneumonia with Hanshi Yidu Xifei syndrome in vivo.Method:Mice were randomly divided into normal group,infection group,cold-dampness group,model group,chloroquine phosphate group(0.18 g·kg^(-1)),interferon-α2b(IFN-α2b)group(1.83×10^(6)U·kg^(-1)),Gegentang granules high-dose and low-dose groups(6.6,3.3 g·kg^(-1))with 10 mice in each group.Cold-dampness environment and hCoV-229E infection were used for modeling,and the general status and lung index of mice in each group were observed.The viral load in lung tissue was detected by real-time fluorescent quantitative polymerase chain reaction(Real-time PCR),the pathological changes in lung tissue were evaluated by hematoxylin-eosin(HE)staining,the levels of serum gastrointestinal hormones and inflammatory factors in lung tissue were detected by enzyme-linked immunosorbent assay(ELISA),and the percentage of peripheral blood lymphocytes was detected by flow cytometry.Result:Comparing with model group,Gegentang granules could significantly alleviate the physical signs of Hanshi Yidu Xifei syndrome,including listlessness,weakness of limbs,sticky stool,etc.Comparing with model group,Gegentang granules high-dose group significantly reduced lung index,histopathological score of interstitial lung and bronchus,and the level of serum motilin(P<0.05,P<0.01),two doses of Gegentang granules could significantly increase the level of serum gastrin(P<0.05,P<0.01),the percentage of CD4^(+),CD8^(+)T lymphocytes in peripheral blood(P<0.05,P<0.01),and the level of tumor necrosis factor-α(TNF-α)in lung tissue was significantly decreased(P<0.01),and the level of interleukin-6(IL-6)showed decreasing tendency.Conclusion:Gegentang granules has therapeutic effect on model mice.It can improve the appearance and behavior characterization,regulate the level of gastrointestinal hormones,decrease lung index and histopathological score,and possibly play an immunomodulatory role by inhibiting the expression of inflammatory cytokines in lung tissue and restoring the percentage of peripheral blood lymphocytes.
作者
耿子涵
鲍岩岩
包蕾
赵荣华
孙静
时宇静
郭姗姗
陶夏莉
高英杰
崔晓兰
GENG Zihan;BAO Yanyan;BAO Lei;ZHAO Ronghua;SUN Jing;SHI Yujing;GUO Shanshan;TAO Xiali;GAO Yingjie;CUI Xiaolan(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Reyoung Pharmaceutical Co.Ltd.,Zibo 256100,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2022年第19期34-41,共8页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家重点研发计划项目(2020YFE0205100)。