
浏览全部资源
扫码关注微信
1.261053 山东 潍坊,潍坊医学院: 基础医学院免疫学教研室
2.261053 山东 潍坊,潍坊医学院: 附属医院肾内科
[彭美玉,E-mail: pmy-107@163.com PENG Meiyu, E-mail: pmy-107@163.com
收稿:2021-09-07,
修回:2021-11-17,
纸质出版:2022-02-28
移动端阅览
沈洁, 张梦雨, 郭振涛, 等. 信筒子醌对系统性红斑狼疮小鼠免疫调节和治疗作用[J]. 陆军军医大学学报, 2022,44(4):363-370.
Jie SHEN, Mengyu ZHANG, Zhentao GUO, et al. Immunomodulatory and therapeutic effects of embelin on systemic lupus erythematosus mice[J]. Journal of Army Medical University, 2022, 44(4): 363-370.
沈洁, 张梦雨, 郭振涛, 等. 信筒子醌对系统性红斑狼疮小鼠免疫调节和治疗作用[J]. 陆军军医大学学报, 2022,44(4):363-370. DOI: 10.16016/j.2097-0927.202109056.
Jie SHEN, Mengyu ZHANG, Zhentao GUO, et al. Immunomodulatory and therapeutic effects of embelin on systemic lupus erythematosus mice[J]. Journal of Army Medical University, 2022, 44(4): 363-370. DOI: 10.16016/j.2097-0927.202109056.
目的
2
观测信筒子醌(Embelin)对系统性红斑狼疮(systemic lupus erythematosus
SLE)小鼠的免疫调节,探讨其对SLE的治疗作用及其机制。
方法
2
腹腔注射0.5 mL降植烷(pristane)构建SLE小鼠模型,检测小鼠尿蛋白水平确认建模成功。将建模成功的SLE小鼠分为对照组和Embelin组,每组5只;对照组采用1% DMSO+PBS灌胃,Embelin组采用50 mg/kg Embelin灌胃,100 μL/次,每周3次。灌胃治疗1个月后,检测淋巴结大小、脾脏指数、肾脏指数,HE染色观察肾脏病理学改变,ELISA法测定血清dsDNA、ssDNA、IgG浓度,流式细胞仪检测Th细胞亚群和B细胞活化指标。
结果
2
与对照组比较,Embelin组SLE小鼠淋巴结大小、脾脏指数、肾脏指数、肾小球平均面积均明显降低(
P
<0.01);Th1/Th2、Treg/Th17比率明显升高(
P
<0.05),B细胞的CD69、CD86、MHC-Ⅱ和Th细胞的CD69、CD154表达水平均明显降低(
P
<0.05);血清中dsDNA、ssDNA和IgG浓度均明显降低(
P
<0.01)。
结论
2
Embelin通过调节Th细胞亚群平衡,抑制Th和B细胞的活化,从而发挥对SLE小鼠的治疗作用。
Objective
2
To observe the immune regulation of embelin against systemic lupus erythematosus (SLE) in mice
so as to investigate its therapeutic effects on SLE and the possible mechanism.
Methods
2
The mouse model of SLE was established by intraperitoneal injection of 0.5 mL pristane
and urine protein level was detected to confirm the success of modeling. SLE mice then were randomly divided into control group and embelin group (
n
=5 for each group). The embelin group was given embelin 50 mg/kg by intragastric gavage
100 μL/time
3 times a week
while the control group was treated with 1% DMSO+PBS instead. After 1 month of administration
the lymph node size
spleen index and renal index of the mice were measured. The renal pathological changes were observed by HE staining; the serum concentrations of dsDNA
ssDNA and IgG were determined by ELISA; the Th cell subsets and B cell activation indexes were detected by flow cytometry.
Results
2
As compared with the control group
the embelin group had significantly reduced lymph node size
spleen index
kidney index
and mean glomerular area (
P
<
0.01)
while elevated ratios of Th1/Th2 and Treg/Th17 (
P
<
0.05). As for the activation markers
the expression levels of CD69
CD86
MHC-Ⅱ in B cells and CD69
CD154 in Th cells were all obviously decreased (
P
<
0.05). In addition
embelin treatment remarkably lowered the concentrations of dsDNA
ssDNA and IgG in serum (
P
<
0.01).
Conclusion
2
Embelin plays a therapeutic role in SLE mice by regulating the balance of Th cell subsets and inhibiting the activation of Th and B cells.
TSAI C Y, LI K J, HSIEH S C, et al . What's wrong with neutrophils in lupus?[J ] . Clin Exp Rheumatol, 2019, 37(4): 684-693.
TSAI C Y, HSIEH S C, LU C S, et al . Cross-talk between mitochondrial dysfunction-provoked oxidative stress and aberrant noncoding RNA expression in the pathogenesis and pathophysiology of SLE[J ] . Int J Mol Sci, 2019, 20(20): 5183. DOI: 10.3390/ijms20205183.
LI M T, ZHAO Y, ZHANG Z Y, et al . 2020 Chinese guidelines for the diagnosis and treatment of systemic lupus erythematosus[J ] . Rheumatol Immunol Res, 2020, 1(1): 5-23. DOI: 10.2478/rir-2020-0009.
BINDA V, TREZZI B, DEL PAPA N, et al . Belimumab may decrease flare rate and allow glucocorticoid withdrawal in lupus nephritis (including dialysis and transplanted patient)[J ] . J Nephrol, 2020, 33(5): 1019-1025. DOI: 10.1007/s40620-020-00706-3.
CHEN H L, SHEN L J, HSU P N, et al . Cumulative burden of glucocorticoid-related adverse events in patients with systemic lupus erythematosus: findings from a 12-year longitudinal study[J ] . J Rheumatol, 2018, 45(1): 83-89. DOI: 10.3899/jrheum.160214.
FANOURIAKIS A, KOSTOPOULOU M, ALUNNO A, et al . 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus[J ] . Ann Rheum Dis, 2019, 78(6): 736-745. DOI: 10.1136/annrheumdis-2019-215089.
WANG Z, WANG Y, ZHU R, et al . Long-term survival and death causes of systemic lupus erythematosus in China: a systemic review of observational studies[J ] . Medicine (Baltimore), 2015, 94(17): e794. DOI: 10.1097/md.0000000000000794.
SHENG Z, GE S, GAO M, et al . Synthesis and bi ological activity of embelin and its derivatives: an overview[J ] . Mini Rev Med Chem, 2020, 20(5): 396-407. DOI: 10.2174/1389557519666191015202723.
彭美玉, 王丽娜, 牟东珍. 信筒子醌升高小鼠胰腺癌CTL、NK、NKT和γδT细胞比例[J]. 基础医学与临床, 2017, 37(8): 1161-1162. DOI: 10.16352/j.issn.1001-6325.2017.08.019.
PENG M Y, WANG L N, MOU D Z. Embelin increased CTL, NK, and ratio of NKT to γδ T cell in pancreatic cancer in mice[J]. Basic Clin Med, 2017, 37(8): 1161-1162. DOI: 10.16352/j.issn.1001-6325.2017.08.019.
XUE Z, GE Z, ZHANG K, et al . Embelin suppresses dendritic cell functions and limits autoimmune encephalomyelitis through the TGF-β/β-catenin and STAT3 signaling pathways[J ] . Mol Neurobiol, 2014, 49(2): 1087-1101. DOI: 10.1007/s12035-013-8583-7.
PENG M, HUANG B, ZHANG Q, et al . Embelin inhibits pancreatic cancer progression by directly inducing cancer cell apoptosis and indirectly restricting IL-6 associated inflammatory and immune suppressive cells[J ] . Cancer Lett, 2014, 354(2): 407-416. DOI: 10.1016/j.canlet.2014.08.011.
FREITAS E C, DE OLIVEIRA M S, MONTICIELO O A. Pristane-induced lupus: considerations on this experimental model[J]. Clin Rheumatol, 2017, 36(11): 2403-2414. DOI: 10.1007/s10067-017-3811-6.
KO J H, LEE S G, YANG W, et al . The application of embelin for cancer prevention and therapy[J ] . Molecules, 2018, 23(3): 621. DOI: 10.3390/molecules23030621.
李荣达, 董莉, 林玲. 诱发性系统性红斑狼疮小鼠模型研究进展[J]. 细胞与分子免疫学杂志, 2013, 29(6): 669-671. DOI: 10.13423/j.cnki.cjcmi.006805.
LI R D, DONG L, LIN L. Progress of mouse model of induced systemic lupus erythematosus[J]. Chin J Cell Mol Immunol, 2013, 29(6): 669-671. DOI: 10.13423/j.cnki.cjcmi.006805.
OSTER C, WILDE B, SPECKER C, et al . BTLA expression on Th1, Th2 and Th17 effector T-cells of patients with systemic lupus erythematosus is associated with active disease[J ] . Int J Mol Sci, 2019, 20(18): 4505. DOI: 10.3390/ijms20184505.
GRAMMER A C, LIPSKY P E. B cell abnormalities in systemic lupus erythematosus[J]. Arthritis Res Ther,2003, 5(Suppl 4): S22-S27. DOI: 10.1186/ar1009.
YAP D Y H, CHAN T M. B cell abnormalities in systemic lupus erythematosus and lupus nephritis—role in pathogenesis and effect of immunosuppressive treatments[J]. Int J Mol Sci, 2019, 20(24): 6231. DOI: 10.3390/ijms20246231.
DOLFF S, BIJL M, HUITEMA M G, et al . Disturbed Th 1, Th2, Th17 and Treg balance in patients with systemic lupus erythematosus[J ] . Clin Immunol, 2011, 141(2): 197-204. DOI: 10.1016/j.clim.2011.08.005.
MUHAMMAD YUSOFF F, WONG K K, MOHD REDZWAN N. Th1, Th2, and Th17 cytokines in systemic lupus erythematosus[J]. Autoimmunity, 2020, 53(1): 8-20. DOI: 10.1080/08916934.2019.1693545.
TALAAT R M, MOHAMED S F, BASSYOUNI I H, et al . Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity[J ] . Cytokine, 2015, 72(2): 146-153. DOI: 10.1016/j.cyto.2014.12.027.
DATTA S K, ZHANG L, XU L T. T-helper cell intrinsic defects in lupus that break peripheral tolerance to nuclear autoantigens[J]. J Mol Med, 2005, 83(4): 267-278. DOI: 10.1007/s00109-004-0624-2.
王元元, 柴继侠, 孙美群, 等. 甘草酸调节MRL/lpr狼疮小鼠的免疫功能及机制[J]. 细胞与分子免疫学杂志, 2017, 33(3): 305-309. DOI: 10.13423/j.cnki.cjcmi.008068.
WANG Y Y, CHAI J X, SUN M Q, et al . Glycyrrhizinic acid modulates the immunity of MRL/lpr mice and related mechanism[J ] . Chin J Cell Mol Immunol, 2017, 33(3): 305-309. DOI: 10.13423/j.cnki.cjcmi.008068.
DOREAU A, BELOT A, BASTID J, et al . Interleukin 17acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus[J ] . Nat Immunol, 2009, 10(7): 778-785. DOI: 10.1038/ni.1741.
WU H Y, QUINTANA F J, WEINER H L. Nasal anti-CD3 antibody ameliorates lupus by inducing an IL-10-secreting CD4 + CD25 - LAP + regulatory T cell and is associated with down-regulation of IL-17 + CD4 + ICOS + CXCR5 + follicular helper T cells[J ] . J Immunol, 2008, 181(9): 6038-6050. DOI: 10.4049/jimmunol.181.9.6038..
LAROSA M, ZEN M, GATTO M, et al . IL-12 and IL-23/Th17 axis in systemic lupus erythematosus[J ] . Exp Biol Med (Maywood), 2019, 244(1): 42-51. DOI: 10.1177/1535370218824547.
OHL K, TENBROCK K. Regulatory T cells in systemic lupus erythematosus[J]. Eur J Immunol, 2015, 45(2): 344-355. DOI: 10.1002/eji.201344280.
SCHEINECKER C, GÖSCHL L, BONELLI M. Treg cells in health and autoimmune diseases: New insights from single cell analysis[J]. J Autoimmun, 2020, 110: 102376. DOI: 10.1016/j.jaut.2019.102376.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621