北五味子总木脂素对环磷酰胺诱导的免疫功能低下小鼠的调节作用
|
摘要
目的:研究北五味子总木脂素(SCL)对环磷酰胺(Cyp)所致免疫抑制小鼠的免疫调节作用,并阐明其作用机制。方法:75只雄性ICR小鼠随机分为对照组,模型组,低、中和高剂量(50、100和200mg·kg-1)SCL组,每组15只。对照组和模型组小鼠灌胃给予同体积的蒸馏水,各剂量SCL组小鼠灌胃给予相应剂量的SCL,连续21d。在给药第17天,模型组和各剂量SCL组小鼠腹腔注射Cyp (20mg·kg-1),对照组小鼠腹腔注射同体积的生理盐水,连续5d。给药结束后,测定各组小鼠胸腺和脾脏指数,并观察胸腺和脾脏组织形态表现,采用碳粒廓清测试法评估巨噬细胞的吞噬功能,采用ELISA法测定γ干扰素(IFN-γ)水平,采用MTT法评价脾淋巴细胞增殖能力,采用流式细胞术检测脾淋巴细胞凋亡率。结果:与对照组比较,模型组小鼠脾脏和胸腺指数、巨噬细胞吞噬指数、IFN-γ水平及淋巴细胞增殖能力明显降低(P<0.05或P<0.01),淋巴细胞早期、晚期和总凋亡率明显升高(P<0.01)。与模型组比较,低、中和高剂量SCL组小鼠脾脏和胸腺指数,巨噬细胞吞噬指数,IFN-γ水平,淋巴细胞增殖能力,淋巴细胞早期、晚期及总凋亡率均明显升高(P<0.05或P<0.01)。与对照组比较,模型组小鼠胸腺皮质淋巴细胞数量减少,脾小体数量和体积明显减少,呈萎缩状态。与模型组比较,各剂量SCL组小鼠胸腺皮质淋巴数量减少、脾小体减少和萎缩均有一定程度改善。结论:SCL可通过调节小鼠细胞、体液和非特异性免疫功能对Cyp诱导的免疫功能低下小鼠起到保护作用。
Objective:To investigate the immunomodulatory effect of Schisandra chinensis lignans(SCL)in the cyclophosphamide(Cyp)-induced immunosuppressive mice, and to elucidate its related mechanisms.Methods:A total of 75 male ICR mice were divided in control group,model group,and low,middle,high doses(50,100,and 200 mg·kg~(-1))of SCL groups,15 mice in each group.The mice in control and model groups were administered with distilled water intragastrically and the mice in SCL groups were administered with different doses of SCL intragastrically once a day for 21 d.After the successive administration for 17 d,the mice in model and SCL groups were intraperitoneally injected with Cyp(20 mg·kg~(-1))once a day for 5 d.The thymus and spleen indexes were determined and the morphology of thymus and spleen tissues were observed.The phagocytic function of macrophages was estimated using carbon clearance test and the level of interferon-γ(IFN-γ)was measured by ELISA method.The spleen lymphocyte proliferation ability was measured by MTT method and the apoptotic rate of spleen lymphocyte was determined by flow cytometry.Results:Compared with control group,the thymus and spleen indexes,the phagocytic function of macrophages,the IFN-γlevel,the spleen lymphocyte proliferation activity,and the early,late,total apoptotic rates of lymphocytes of the mice in model group were increased(P<0.05 or P<0.01).Compared with model group,the thymus and spleen indexes,the phagocytic function of macrophages,the IFN-γlevels,the spleen lymphocyte proliferation abilities,and the early,late,total apoptotic rates of lymphocytes of the mice in different doses of SCL groups were significantly decreased(P<0.05 or P<0.01).Compared with control group,the number of lymphocytes in the thymus cortex of the mice in model group was reduced,the number of splenic corpuscles was reduced and their volumes were obviously reduced.Compared with model group,the reducing of lymphocyte number in the thymus cortex and splenic corpuscles and atrophy of the mice in different doses of SCL groups were obviously improved.Conclusion:SCL can protect the mice with Cypinduced immunodeficiency by regulating the cellular,humoral and non-specific immune functions of the mice.
Objective:To investigate the immunomodulatory effect of Schisandra chinensis lignans(SCL)in the cyclophosphamide(Cyp)-induced immunosuppressive mice, and to elucidate its related mechanisms.Methods:A total of 75 male ICR mice were divided in control group,model group,and low,middle,high doses(50,100,and 200 mg·kg~(-1))of SCL groups,15 mice in each group.The mice in control and model groups were administered with distilled water intragastrically and the mice in SCL groups were administered with different doses of SCL intragastrically once a day for 21 d.After the successive administration for 17 d,the mice in model and SCL groups were intraperitoneally injected with Cyp(20 mg·kg~(-1))once a day for 5 d.The thymus and spleen indexes were determined and the morphology of thymus and spleen tissues were observed.The phagocytic function of macrophages was estimated using carbon clearance test and the level of interferon-γ(IFN-γ)was measured by ELISA method.The spleen lymphocyte proliferation ability was measured by MTT method and the apoptotic rate of spleen lymphocyte was determined by flow cytometry.Results:Compared with control group,the thymus and spleen indexes,the phagocytic function of macrophages,the IFN-γlevel,the spleen lymphocyte proliferation activity,and the early,late,total apoptotic rates of lymphocytes of the mice in model group were increased(P<0.05 or P<0.01).Compared with model group,the thymus and spleen indexes,the phagocytic function of macrophages,the IFN-γlevels,the spleen lymphocyte proliferation abilities,and the early,late,total apoptotic rates of lymphocytes of the mice in different doses of SCL groups were significantly decreased(P<0.05 or P<0.01).Compared with control group,the number of lymphocytes in the thymus cortex of the mice in model group was reduced,the number of splenic corpuscles was reduced and their volumes were obviously reduced.Compared with model group,the reducing of lymphocyte number in the thymus cortex and splenic corpuscles and atrophy of the mice in different doses of SCL groups were obviously improved.Conclusion:SCL can protect the mice with Cypinduced immunodeficiency by regulating the cellular,humoral and non-specific immune functions of the mice.
引文
[1]CHENG D,WAN Z D,ZHANG X Y,et al.Dietary chlorella vulgaris ameliorates altered immunomodulatory functions in cyclophosphamide-induced immunosuppressive mice[J].Nutrients,2017,9(7):E708.
[2]史晶晶,时博,苗明三.黄芪多糖对环磷酰胺致免疫抑制小鼠免疫功能的影响[J].中医学报,2016,31(2):243-246.
[3]张海玉,朴惠顺,金在久,等.参芪合剂对环磷酰胺所致免疫抑制小鼠免疫和抗氧化功能的影响[J].吉林大学学报:医学版,2009,35(5):857-861.
[4]BO R N,SUN Y Q,ZHOU S Z,et al.Simple nanoliposomes encapsulating Lycium barbarum polysaccharides as adjuvants improve humoral and cellular immunity in mice[J].Int JNanomedicine,2017,12:6289-6301.
[5]张旻昱,吴宏伟,许利平,等.五味子及其活性成分治疗心脑血管疾病药理作用的研究进展[J].中国中药杂志,2018,43(8):1536-1546.
[6]PANOSSIAN A,WIKMAN G.Pharmacology of Schisandra chinensis Bail.:An overview of Russian research and uses in medicine[J].J Ethnopharmacol,2008,118(2):183-212.
[7]郭志欣,朱俊义,顾地周,等.五味子药渣多糖的提取及其免疫活性[J].东北林业大学学报,2016,44(12):80-82.
[8]张琨琨.五味子多糖免疫调节及抗氧化功能研究[J].职业卫生与病伤,2016,31(1):54-57.
[9]SUN J H,JING S,JIANG R,et al.Metabolomics study of the therapeutic mechanism of Schisandra chinensis lignans on aging rats induced by d-galactose[J].Clin Interv Aging,2018,13:829-841.
[10]于雷,王蕴龙,陈志深,等.鹿角脱盘对辐射诱发小鼠胸腺淋巴瘤Notch2基因表达和免疫功能的影响[J].吉林大学学报:医学版,2016,42(5):887-891.
[11]LIU J,QI Y J,ZHENG L,et al.Xinfeng capsule improves pulmonary function in ankylosing spondylitis patients via NF-κB-iNOS-NO signaling pathway[J].J Tradit Chin Med,2014,34(6):657-665.
[12]WANG E L,CHEN X,WANG K Y,et al.Plant polysaccharides used as immunostimulants enhance innate immune response and disease resistance against Aeromonas hydrophila infection in fish[J].Fish Shellfish Immunol,2016,59:196-202.
[13]ZHAO T,FENG Y,LI J,et al.Schisandra polysaccharide evokes immunomodulatory activity through TLR 4-mediated activation of macrophages[J].Int J Biol Macromol,2014,65:33-40.
[14]SHENG X T,YAN J M,MENG Y,et al.Immunomodulatory effects of Hericium erinaceus derived polysaccharides are mediated by intestinal immunology[J].Food Funct,2017,8(3):1020-1027.
[15]YANG L C,LU T J,HSIEH C C,et al.Characterization and immunomodulatory activity of polysaccharides derived from Dendrobium tosaense[J].Carbohydr Polym,2014,111:856-863.
[16]CAO Q F,QU M J,YANG W Q,et al.Ischemia postconditioning preventing lung ischemia-reperfusion injury[J].Gene,2015,554(1):120-124.
[17]ABDUR RAHMAN K,BINABDULHAK A A,ALASTALY,et al.Cardioprotective role of ischemic postconditioning in acute myocardial infarction:A systematic review and metaanalysis[J].Am Heart,2014,168(4):512-521,e4.
[18]XING J,XIAO Y E,TANG X Q,et al.Inhibition of Cyclosporine A or rapamycin on T lymphocyte counts and the influence on the immune responses of B lymphocytes in flounder(Paralichthys olivaceus)[J].Fish Shellfish Immunol,2017,66:78-85.
[19]HUANG C,SONG K K,MA W W,et al.Immunomodulatory mechanism of Bushen Huoxue Recipe alleviates cyclophosphamide-induced diminished ovarian reserve in mouse model[J].J Ethnopharmacol,2017,208:44-56.
[20]奚小土,刘云涛,曾瑞峰,等.益气温阳对脓毒症内质网应激途径淋巴细胞凋亡的作用[J].暨南大学学报:自然科学与医学版,2017,38(6):475-480.
[21]陈斌,张涛,朱文芳,等.清温并用法对慢加急性肝衰竭大鼠调节性T淋巴细胞/辅助性T淋巴细胞17表达的影响[J].临床肝胆病杂志,2018,34(12):2642-2647.
[22]吴田田,姚咏明.脓毒症免疫紊乱及其临床意义[J].解放军医学杂志,2017,42(2):95-102.
[2]史晶晶,时博,苗明三.黄芪多糖对环磷酰胺致免疫抑制小鼠免疫功能的影响[J].中医学报,2016,31(2):243-246.
[3]张海玉,朴惠顺,金在久,等.参芪合剂对环磷酰胺所致免疫抑制小鼠免疫和抗氧化功能的影响[J].吉林大学学报:医学版,2009,35(5):857-861.
[4]BO R N,SUN Y Q,ZHOU S Z,et al.Simple nanoliposomes encapsulating Lycium barbarum polysaccharides as adjuvants improve humoral and cellular immunity in mice[J].Int JNanomedicine,2017,12:6289-6301.
[5]张旻昱,吴宏伟,许利平,等.五味子及其活性成分治疗心脑血管疾病药理作用的研究进展[J].中国中药杂志,2018,43(8):1536-1546.
[6]PANOSSIAN A,WIKMAN G.Pharmacology of Schisandra chinensis Bail.:An overview of Russian research and uses in medicine[J].J Ethnopharmacol,2008,118(2):183-212.
[7]郭志欣,朱俊义,顾地周,等.五味子药渣多糖的提取及其免疫活性[J].东北林业大学学报,2016,44(12):80-82.
[8]张琨琨.五味子多糖免疫调节及抗氧化功能研究[J].职业卫生与病伤,2016,31(1):54-57.
[9]SUN J H,JING S,JIANG R,et al.Metabolomics study of the therapeutic mechanism of Schisandra chinensis lignans on aging rats induced by d-galactose[J].Clin Interv Aging,2018,13:829-841.
[10]于雷,王蕴龙,陈志深,等.鹿角脱盘对辐射诱发小鼠胸腺淋巴瘤Notch2基因表达和免疫功能的影响[J].吉林大学学报:医学版,2016,42(5):887-891.
[11]LIU J,QI Y J,ZHENG L,et al.Xinfeng capsule improves pulmonary function in ankylosing spondylitis patients via NF-κB-iNOS-NO signaling pathway[J].J Tradit Chin Med,2014,34(6):657-665.
[12]WANG E L,CHEN X,WANG K Y,et al.Plant polysaccharides used as immunostimulants enhance innate immune response and disease resistance against Aeromonas hydrophila infection in fish[J].Fish Shellfish Immunol,2016,59:196-202.
[13]ZHAO T,FENG Y,LI J,et al.Schisandra polysaccharide evokes immunomodulatory activity through TLR 4-mediated activation of macrophages[J].Int J Biol Macromol,2014,65:33-40.
[14]SHENG X T,YAN J M,MENG Y,et al.Immunomodulatory effects of Hericium erinaceus derived polysaccharides are mediated by intestinal immunology[J].Food Funct,2017,8(3):1020-1027.
[15]YANG L C,LU T J,HSIEH C C,et al.Characterization and immunomodulatory activity of polysaccharides derived from Dendrobium tosaense[J].Carbohydr Polym,2014,111:856-863.
[16]CAO Q F,QU M J,YANG W Q,et al.Ischemia postconditioning preventing lung ischemia-reperfusion injury[J].Gene,2015,554(1):120-124.
[17]ABDUR RAHMAN K,BINABDULHAK A A,ALASTALY,et al.Cardioprotective role of ischemic postconditioning in acute myocardial infarction:A systematic review and metaanalysis[J].Am Heart,2014,168(4):512-521,e4.
[18]XING J,XIAO Y E,TANG X Q,et al.Inhibition of Cyclosporine A or rapamycin on T lymphocyte counts and the influence on the immune responses of B lymphocytes in flounder(Paralichthys olivaceus)[J].Fish Shellfish Immunol,2017,66:78-85.
[19]HUANG C,SONG K K,MA W W,et al.Immunomodulatory mechanism of Bushen Huoxue Recipe alleviates cyclophosphamide-induced diminished ovarian reserve in mouse model[J].J Ethnopharmacol,2017,208:44-56.
[20]奚小土,刘云涛,曾瑞峰,等.益气温阳对脓毒症内质网应激途径淋巴细胞凋亡的作用[J].暨南大学学报:自然科学与医学版,2017,38(6):475-480.
[21]陈斌,张涛,朱文芳,等.清温并用法对慢加急性肝衰竭大鼠调节性T淋巴细胞/辅助性T淋巴细胞17表达的影响[J].临床肝胆病杂志,2018,34(12):2642-2647.
[22]吴田田,姚咏明.脓毒症免疫紊乱及其临床意义[J].解放军医学杂志,2017,42(2):95-102.