枸杞多糖对免疫低下小鼠肺炎克雷伯菌感染的实验研究  

Effects of Lycium Barbarum Polysaccharides on Klebsiella Pneumoniae Infection in Immunocompromised Mice

作　　者：徐珍 何冰瑶 王玮琪 李松樯 马东菊 熊莉晶 宋银宏[4] 苏维敏 周永芹[2,3,4] XÜZhen;HE Bingyao;WANG Weiqi;LI Songqiang;MA Dongjü;XIONG Lijing;SONG Yinhong;SU Weimin;ZHOU Yongqin(Renhe Hospital of China Three Gorges University,Yichang 443000,China;Hubei Province Clinical Medical Research Center for Precision Prevention and Treatment of Gastrointestinal Cancer in the Elderly,The Second People's Hospital Affiliated to China Three Gorges University,Yichang 443000,China;Hubei Key Laboratory of Research and Utilization of Natural Products,China Three Gorges University,Yichang 443000,China;Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy,China Three Gorges University,Yichang 443000,China;Yichang Central People's Hospital,People's Hospital of China Three Gorges University,Yichang 443000,China)

机构地区：[1]三峡大学仁和医院,湖北宜昌443000 [2]湖北省老年胃肠癌精准防治临床医学研究中心,三峡大学附属第二人民医院,湖北宜昌443000 [3]天然产物研究与利用湖北省重点实验室,三峡大学,湖北宜昌443000 [4]肿瘤微环境与免疫治疗湖北省重点实验室,三峡大学,湖北宜昌443000 [5]宜昌市中心人民医院,三峡大学人民医院,湖北宜昌443000

出　　处：《中国药学杂志》2025年第4期363-372,共10页Chinese Pharmaceutical Journal

基　　金：湖北省老年胃肠癌精准防治临床医学研究中心开放基金项目资助(2022EGC-10);宜昌市医疗卫生科研项目资助(A24-2-058);肿瘤微环境与免疫治疗湖北省重点实验室(三峡大学)开放基金项目资助(2023KZL028);天然产物研究与利用湖北省重点实验室(三峡大学)开放基金项目资助(NPRD-2018012)。

摘　　要：目的本研究旨在探讨枸杞多糖(Lycium barbarum polysaccharide,LBP)对免疫低下小鼠机会致病性肺炎克雷伯菌感染的影响。方法采用环磷酰胺制备免疫低下小鼠模型,并随机分为肺炎模型组、LBP高(40 mg·kg^(-1))、中(20 mg·kg^(-1))、低(10 mg·kg^(-1))剂量组,同时设正常对照组。通过滴鼻给予肺炎克雷伯菌(Klebsiella pneumoniae,KP)菌液制备肺炎小鼠模型,同时各组小鼠灌胃给予相应浓度的LBP,每日一次,持续10 d,对照组和模型组则给予等量生理盐水。实验期间,监测小鼠一般状态、体质量和生存率。实验结束,取小鼠的肺脏、脾脏、胸腺和肝脏,计算内脏指数;同时分析肺组织载菌量和组织病理;检测中性粒细胞吞噬能力、脾脏淋巴细胞亚群及增殖能力,以评估小鼠免疫功能。结合炎症相关细胞因子和氧化应激活性的分析,进一步揭示其作用机制。结果模型组小鼠的一般状态、体质量-和生存率均明显降低,同时伴随着中性粒细胞吞噬指数的显著下调,脾脏淋巴细胞总数、总T细胞、辅助性T细胞(T helper cell,Th)和B细胞含量也显著降低,髓过氧化物酶(myeloperoxidase,MPO)和超氧化物歧化酶(superoxide dismutase,SOD)活性低下,共同证明了免疫低下模型的制备成功。然而,经过不同剂量的LBP处理后,结果显示LBP可有效改善免疫低下合并KP感染肺炎小鼠一般状态和生存率。小鼠的肺脏指数较模型组明显降低(P<0.05),表明肺部炎症减轻;肺组织匀浆载菌量显著降低,组织病理分析显示肺泡结构相对完整、充血及炎性渗出减少。同时,治疗组小鼠的淋巴细胞总数、总T细胞、Th和B细胞含量较模型组升高(P<0.05),且高剂量组的差异具有显著性。此外,LBP组还呈现出明显提升的中性粒细胞吞噬指数和淋巴细胞增殖率,以及恢复的MPO和SOD活性,共同说明LBP具有免疫增强作用,进而发挥抗感染效应。最后,相较于模型组紊乱的血�OBJECTIVE To explore the effects of Lycium barbarum polysaccharides(LBP)on opportunistic pathogenic Klebsiella pneumoniae infection in immunocompromised mice.METHODS Immunocompromised mouse models were constructed using cyclophosphamide,then randomly divided these mice into a pneumonia model group,high-dose LBP group(40 mg·kg^(-1)),medium-dose LBP group(20 mg·kg^(-1)),low-dose LBP group(10 mg·kg^(-1)),and a normal control group.Pneumonia mouse models were constructed by intranasal administration of Klebsiella pneumoniae(KP)bacterial solution.Mice in LBP-treated groups were administered LBP at corresponding concentrations through gavage once daily for 10 days,while the control and model group mice were given equal volumes of normal saline.During the experiment,the general condition,body weight,and survival rate of the mice were monitored.After the experiment,the lungs,spleen,thymus,and liver of the mice were collected to calculate the organ index.The lung tissue bacterial load and histopathology were analyzed,and the phagocytic capacity of neutrophils,spleen lymphocyte subsets,and proliferative capacity were detected to evaluate the immune function of the mice.Combined with the analysis of inflammation-related cytokines and oxidative stress activity,the mechanism of action was further revealed.RESULTS The general condition,body weight,and survival rate of mice in the model group were significantly decreased,accompanied by a significant downregulation of the neutrophil phagocytic index,a significant reduction in the total number of spleen lymphocytes,total T cells,T helper cells(Th),and B cells,as well as decreased myeloperoxidase(MPO)and superoxide dismutase(SOD)activity,collectively demonstrating the successful preparation of the immunocompromised model.However,after treatment with different doses of LBP,the results showed that LBP could effectively improve the general condition and survival rate of immunocompromised mice with KP-infected pneumonia.The lung index of mice in the LBP treatment groups was signifi

关 键 词：枸杞多糖 免疫低下 肺炎克雷伯菌 免疫调节 抗感染 

分 类 号：R966[医药卫生—药理学]