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1.635000 四川 达州,达州中医药职业学院:中医系
2.635000 四川 达州,达州中医药职业学院:药学系
[许孟霞,E-mail:xmx386159963@163.comXU Mengxia, E-mail: xmx386159963@163.com
收稿:2021-12-03,
修回:2022-02-08,
纸质出版:2022-06-30
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许孟霞, 黄忠明, 唐洪英, 等. 香叶木素缓解MRL/lpr狼疮性肾炎小鼠肾炎症反应的作用及可能机制[J]. 陆军军医大学学报, 2022,44(12):1237-1242.
Mengxia XU, Zhongming HUANG, Hongying TANG, et al. Role and possible mechanism of diosmetin in alleviating nephritis response in MRL/lpr lupus nephritis mice[J]. Journal of Army Medical University, 2022, 44(12): 1237-1242.
许孟霞, 黄忠明, 唐洪英, 等. 香叶木素缓解MRL/lpr狼疮性肾炎小鼠肾炎症反应的作用及可能机制[J]. 陆军军医大学学报, 2022,44(12):1237-1242. DOI: 10.16016/j.2097-0927.202112027.
Mengxia XU, Zhongming HUANG, Hongying TANG, et al. Role and possible mechanism of diosmetin in alleviating nephritis response in MRL/lpr lupus nephritis mice[J]. Journal of Army Medical University, 2022, 44(12): 1237-1242. DOI: 10.16016/j.2097-0927.202112027.
目的
2
探讨香叶木素对狼疮性肾炎的保护作用及其可能的机制。
方法
2
将10只C57BL/6小鼠作为对照组,50只MRL/lpr狼疮性肾炎小鼠按随机数字表法分为MRL/lpr组、地塞米松组、香叶木素低剂量组(0.25 mg/kg)、香叶木素中剂量组(0.50 mg/kg)和香叶木素高剂量组(1.00 mg/kg),每组10只。连续7 d腹腔注射给药,取所有小鼠血清及肾脏组织。HE染色观察肾组织形态学变化。试剂盒检测血清肌酐、血尿素氮和血清抗双链DNA抗体水平,以及血清和肾组织中IL-1β、IL-6和TNF-α表达水平。Western blot检测肾组织中NLRP3、ASC、Caspase-1、IL-1β、p-NF-κB和p-IκBα蛋白表达。
结果
2
与MRL/lpr组相比,香叶木素中、高剂量组和地塞米松组小鼠肾组织中炎性细胞浸润减少,且小鼠血清肌酐、血尿素氮和血清抗双链DNA抗体的水平均显著降低(
P
<
0.05),小鼠血清和肾脏组织中IL-1β、IL-6和TNF-α的蛋白表达均显著降低(
P
<
0.05)。与MRL/Lpr组相比,香叶木素中、高剂量组和地塞米松组小鼠肾组织中NLRP3、ASC、Caspase-1、IL-1β和p-NF-κB的蛋白表达均显著降低(
P
<
0.05),而p-IκBα蛋白表达显著升高(
P
<
0.05)。
结论
2
香叶木素对MRL/lpr小鼠肾脏具有一定保护作用,其机制可能与抑制NLRP3和NF-κB信号通路有关。
Objective
2
To investigate the protective effect of diosmetin on lupus nephritis and its possible mechanism.
Methods
2
Ten C57BL/6 mice were used as control group
and 50 MRL/lpr lupus mice were randomly divided into MRL/lpr group
dexamethasone group
and 3 doses of diosmetin groups (0.25
0.50 and 1.00 mg/kg). After intraperitoneal injection for 7 d
the serum and kidney tissues of all mice were collected. HE staining was used to observe the morphological changes of the kidneys. Corresponding kits were used to measure the levels of serum creatinine
blood urea nitrogen
and serum anti-double-stranded DNA antibody
as well as the expression levels of IL-1β
IL-6
and TNF-α in the serum and renal tissue. The protein levels of NLRP3
ASC
Caspase-1
IL-1β
p-NF-κB and p-IκBα in renal tissues were detected by Western blotting.
Results
2
Compared with the MRL/lpr group
the medium and high dose diosmetin groups and the dexamethasone group had reduced infiltration of inflammatory cells in the kidney tissue
and significantly decreased levels of serum creatinine
blood urea nitrogen and serum anti-double-chain DNA antibody (
P
<
0.05). Meanwhile
the protein expression levels of IL-1β
IL-6 and TNF-α in the serum and kidney tissues were also significantly decreased (
P
<
0.05). Compared with the MRL/lpr group
the protein levels of NLRP3
ASC
Caspase-1
IL-1β and p-NF-κB were remarkably decreased (
P
<
0.05)
while that of p-IκBα was notably increased in the medium and high dose diosemetin groups and the dexamethasone group(
P
<
0.05).
Conclusion
2
Diosmetin has a protective effect on the kidney of MRL/lpr mice
and the mechanism may be related to the inhibition of NLRP3 and NF-κB signaling pathway.
AIRY M, EKNOYAN G. Lupus nephritis: a historical appraisal of how a skin lesion became a kidney disease[J]. Clin Nephrol, 2019, 91(6): 325-333. DOI: 10.5414/CN109675.
韦婷婷, 黄雪霞, 李丽容, 等. 中医药治疗狼疮性肾炎的研究进展[J]. 湖南中医杂志, 2021, 37(9): 194-196. DOI: 10.16808/j.cnki.issn1003-7705.2021.09.062.
WEI T T, HUANG X X, LI L R, et al . Research progress on treatment of lupus nephritis with traditional chinese medicine[J ] . Hunan J Tradit Chin Med, 2021, 37(9): 194-196. DOI: 10.16808/j.cnki.issn1003-7705.2021.09.062.
JOLLY M, TOLOZA S, GOKER B, et al . Disease-specific quality of life in patients with lupus nephritis[J ] . Lupus, 2018, 27(2): 257-264. DOI: 10.1177/0961203317717082.
MEIRINHOS J, SILVA B M, VALENTÃO P, et al . Analysis and quantification of flavonoidic compounds from Portuguese olive (Olea europaea L. ) leaf cultivars[J ] . Nat Prod Res, 2005, 19(2): 189-195. DOI: 10.1080/14786410410001704886.
ZHANG Y, JIANG Y L, LU D J. Diosmetin suppresses neuronal apoptosis and inflammation by modulating the phosphoinositide 3-kinase (PI3K)/AKT/nuclear factor-κB (NF-κB) signaling pathway in a rat model of pneumococcal meningitis[J]. Med Sci Monit, 2019, 25: 2238-2245. DOI: 10.12659/MSM.911860.
陈新亮, 陈志宝. 香叶木素改善顺铂诱导的鼠肾小管上皮细胞的损伤[J]. 黑龙江八一农垦大学学报, 2021, 33(5): 93-99. DOI: 10.3969/j.issn.1002-2090.2021.05.015.
CHEN X L, CHEN Z B. Diosmetin improvement cisplatin-induced damage to rat renal tubular epithelial cells[J]. J Heilongjiang August First Land Reclam Univ, 2021, 33(5): 93-99. DOI: 10.3969/j.issn.1002-2090.2021.05.015.
王元元, 李洪涛, 陆杨, 等. 甘草酸对MRL/lpr小鼠狼疮性肾炎的治疗作用[J]. 南方医科大学学报, 2017, 37 (7): 957-961. DOI: 10.3969/j.issn.1673-4254.2017.07.19.
WANG Y Y, LI H T, LU Y, et al . Protective effects of glycyrrhizic acid against lupus nephritis in MRL/lpr mice[J ] . J South Med Univ, 2017, 37(7): 957-961. DOI: 10.3969/j.issn.1673-4254.2017.07.19.
YANG K, LI W F, YU J F, et al . Diosmetin protects against ischemia/reperfusion-induced acute kidney injury in mice[J ] . J Surg Res, 2017, 214: 69-78. DOI: 10.1016/j.jss.2017.02.067.
DANG W Z, LI H, JIANG B, et al . Therapeutic effects of artesunate on lupus-prone MRL/lpr mice are dependent on T follicular helper cell differentiation and activation of JAK2-STAT3 signaling pathway[J ] . Phytomedicine, 2019, 62: 152965. DOI: 10.1016/j.phymed.2019. 152965.
LI Q R, TAN S R, XU K, et al . Curcumin attenuates lupus nephritis in MRL/lpr mice by suppressing macrophage-secreted B cell activating factor (BAFF)[J ] . Int J Clin Exp Pathol, 2019, 12(6): 2075-2083.
LIU Q M, CI X X, WEN Z M, et al . Diosmetin alleviates lipopolysaccharide-induced acute lung injury through activating the Nrf2 pathway and inhibiting the NLRP3 inflammasome[J ] . Biomol Ther (Seoul), 2018, 26(2): 157-166. DOI: 10.4062/biomolther.2016.234.
YANG Y, GONG X B, HUANG L G, et al . Diosmetin exerts anti-oxidative, anti-inflammatory and anti-apoptotic effects to protect against endotoxin-induced acute hepatic failure in mice[J ] . Oncotarget, 2017, 8(19): 30723-30733. DOI: 10.18632/oncotarget.15413.
SONG N, LI T. Regulation of NLRP3 inflammasome by phosphorylation[J]. Front Immunol, 2018, 9: 2305. DOI: 10.3389/fimmu.2018.02305.
张清平, 陈永旺. 栀子苷通过抑制NLRP3炎症小体激活治疗MRL/lpr小鼠狼疮性肾炎[J]. 中国免疫学杂志, 2021, 37(17): 2082-2086. DOI: 10.3969/j.issn.1000-484X.2021.17.007.
ZHANG Q P, CHEN Y W. Geniposide treats MRL/lpr mice lupus hephritis by inhibiting NLRP3 inflammasome activation[J]. Chin J Immunol, 2021, 37(17): 2082-2086. DOI: 10.3969/j.issn.1000-484X.2021.17.007.
ZHAO J J, WANG J H, ZHOU M J, et al . Curcumin attenuates murine lupus via inhibiting NLRP3 inflammasome[J ] . Int Immunopharmacol, 2019, 69: 213-216. DOI: 10.1016/j.intimp.2019.01.046.
HE J H, SUN M C, TIAN S J. Procyanidin B2 prevents lupus nephritis development in mice by inhibiting NLRP3 inflammasome activation[J]. Innate Immun, 2018, 24(5): 307-315. DOI: 10.1177/1753425918780985.
PENG X, YANG T, LIU G, et al . Piperine ameliorated lupus nephritis by targeting AMPK-mediated activation of NLRP3 inflammasome[J ] . Int Immunopharmacol, 2018, 65: 448-457. DOI: 10.1016/j.intimp.2018.10.025.
CHALMERS S A, GARCIA S J, REYNOLDS J A, et al . NF-kB signaling in myeloid cells mediates the pathogenesis of immune-mediated nephritis[J ] . J Autoimmun, 2019, 98: 33-43. DOI: 10.1016/j.jaut.2018.11.004.
BAEUERLE P A, BALTIMORE D. A 65-kappaD subunit of active NF-kappaB is required for inhibition of NF-kappaB by I kappaB[J]. Genes Dev, 1989, 3(11): 1689-1698. DOI: 10.1101/gad.3.11.1689.
SU B F, YE H, YOU X H, et al . Icariin alleviates murine lupus nephritis via inhibiting NF-κB activation pathway and NLRP3 inflammasome[J ] . Life Sci, 2018, 208: 26-32. DOI: 10.1016/j.lfs.2018.07.009..
YU G, WAN R, YIN G J, et al . Diosmetin ameliorates the severity of cerulein-induced acute pancreatitis in mice by inhibiting the activation of the nuclear factor-κB[J ] . Int J Clin Exp Pathol, 2014, 7(5): 2133-2142.
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