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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

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【作者】 徐珍何冰瑶王玮琪李松樯马东菊熊莉晶宋银宏苏维敏周永芹

【Author】 Xü Zhen;HE Bingyao;WANG Weiqi;LI Songqiang;MA Dongjü;XIONG Lijing;SONG Yinhong;SU Weimin;ZHOU Yongqin;Renhe Hospital of China Three Gorges University;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;Hubei Key Laboratory of Research and Utilization of Natural Products, China Three Gorges University;Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University;Yichang Central People′s Hospital, People′s Hospital of China Three Gorges University;

【通讯作者】 苏维敏;周永芹;

【机构】 三峡大学仁和医院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天然产物研究与利用湖北省重点实验室,三峡大学肿瘤微环境与免疫治疗湖北省重点实验室,三峡大学宜昌市中心人民医院,三峡大学人民医院

【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清细胞因子水平,LBP对异常升高的炎性细胞因子干扰素(interferon, IFN)-γ、肿瘤坏死因子(tumor necrosis factor, TNF)-α和白细胞介素(interleukin, IL)-6水平呈现剂量依赖性的下调。结论 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。具体表现为降低肺组织载菌量、缓解肺组织病理损伤,伴随升高的淋巴细胞数量和增殖能力,增强中性粒细胞吞噬能力,纠正失衡的细胞因子水平和氧化应激水平等,共同提高免疫低下小鼠的免疫功能及抗感染能力,发挥免疫保护和免疫调节作用。

【Abstract】 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 significantly lower than that in the model group(P<0.05), indicating reduced lung inflammation. The lung tissue homogenate bacterial load was significantly decreased, and histopathological analysis showed relatively intact alveolar structure, reduced congestion, and decreased inflammatory exudation. At the same time, the total number of lymphocytes, total T cells, Th, and B cells in the treatment groups were increased compared with the model group(P<0.05), with significant differences in the high-dose group. In addition, the LBP groups also showed obviously increased neutrophil phagocytic index and lymphocyte proliferation rate, as well as restored MPO and SOD activity, collectively indicating that LBP has an immune-enhancing effect and exerts an anti-infective effect. Finally, compared with the disordered serum cytokine levels in the model group, LBP showed a dose-dependent downregulation of abnormally elevated inflammatory cytokines interferon(IFN)-γ, tumor necrosis factor(TNF)-α, and interleukin(IL)-6 levels. CONCLUSION LBP can effectively improve the general condition and survival rate of immunocompromised mice with KP-infected pneumonia. Specifically, it reduces lung tissue bacterial load, alleviates lung tissue pathological damage, increases lymphocyte count and proliferative capacity, enhances neutrophil phagocytic capacity, corrects imbalanced cytokine levels and oxidative stress levels, etc., collectively improving the immune function and anti-infective ability of immunocompromised mice and exerting immune protection and immunomodulatory effects.

【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)
  • 【文献出处】 中国药学杂志 ,Chinese Pharmaceutical Journal , 编辑部邮箱 ,2025年04期
  • 【分类号】R285.5
  • 【下载频次】142
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