[1]谢良山,安 阳,张 军,等.松萝酸对CIA大鼠HMGB1、自噬蛋白Beclin1及炎性因子的影响[J].医学信息,2023,36(16):78-83.[doi:10.3969/j.issn.1006-1959.2023.16.014]
　XIE Liang-shan,AN Yang,ZHANG Jun,et al.Effects of Ursolic Acid on HMGB1, Autophagy Protein Beclin1 and Inflammatory Factors in CIA Rats[J].Journal of Medical Information,2023,36(16):78-83.[doi:10.3969/j.issn.1006-1959.2023.16.014]
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松萝酸对CIA大鼠HMGB1、自噬蛋白Beclin1及炎性因子的影响()
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医学信息[ISSN:1006-1959/CN:61-1278/R]

卷:
36卷
期数:
2023年16期
页码:
78-83
栏目:
论著
出版日期:
2023-08-15

文章信息/Info

Title:
Effects of Ursolic Acid on HMGB1, Autophagy Protein Beclin1 and Inflammatory Factors in CIA Rats
文章编号:
1006-1959（2023）16-0078-06
作者:
谢良山; 安 阳; 张 军; 等
（1.贵州中医药大学第二临床医学院，贵州 贵阳 550002；2.贵州中医药大学第二附属医院风湿免疫科，贵州 贵阳 550001）
Author(s):
XIE Liang-shan; AN Yang; ZHANG Jun; et al.
(1.The Second Clinical Medical College of Guizhou University of Traditional Chinese Medicine,Guiyang 550002,Guizhou,China; 2.Department of Rheumatology and Immunology,Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001,Guizhou,China)
关键词:
类风湿关节炎; HMGB1; 自噬蛋白Beclin1; 炎性因子; 松萝酸
Keywords:
Rheumatoid arthritis; HMGB1; Autophagy protein Beclin1; Inflammatory factor; Ursolic acid
分类号:
R539.22
DOI:
10.3969/j.issn.1006-1959.2023.16.014
文献标志码:
A
摘要:
目的 探讨松萝酸对关节炎（CIA）大鼠HMGB1、自噬蛋白Beclin1及炎性因子的影响。方法 将72只大鼠随机分成6组，每组12只，即空白对照组、模型对照组、阳性对照组、松萝酸低、中、高剂量组，各组采用Ⅱ型胶原乳剂造模成CIA大鼠模型，空白对照组除外。造模结束后，用低（2 mg/kg）、中（6 mg/kg）、高（54 mg/kg）剂量组的松萝酸进行药物干预治疗，阳性对照组给予羟氯喹（36 mg/kg），空白对照组及模型对照组予等溶剂5 ml蒸馏水灌胃。所有大鼠每天给药1次，连续给药28 d。末次灌胃2 h后，提取标本，观察大鼠关节指数评分、肿胀程度测定，透射电镜观察细胞自噬，采用ELISA检测HMGB1、TNF-α、IL-1、INF-γ的血清浓度水平，PCR、WB检测蛋白HMGB1、Beclin1、Bcl-2、PI3K蛋白表达情况。结果 模型对照组血清HMGB1、TNF-α、IL-1、INF-γ含量高于空白对照组，滑膜组织中HMGB1、Bcl-2、PI3K蛋白水平高于空白对照组，Beclin1蛋白表达量低于空白对照组，差异有统计学意义（P＜0.05）；松萝酸中、高剂量组及阳性对照组HMGB1、TNF-α、IL-1、INF-γ、Bcl-2、PI3K水平低于模型对照组，Beclin1蛋白表达量高于模型对照组，差异有统计学意义（P＜0.05）；松萝酸中、高剂量组抑制HMGB1、Bcl-2、PI3K表达、激活Beclin1的效果与阳性对照组比较，差异无统计学意义（P＞0.05）。结论 松萝酸能减轻CIA大鼠关节肿胀程度，降低血清HMGB1、TNF-α、IL-1、INF-γ浓度，抑制HMGB1、Bcl-2、PI3K蛋白的表达，促进Beclin1表达上升，增强细胞自噬，减少滑膜炎症反应。
Abstract:
Objective To explore the effect of ursolic acid on HMGB1, autophagy protein Beclin1 and inflammatory factors in CIA rats.Methods A total of 72 rats were randomly divided into 6 groups, with 12 rats in each group: blank control group, model control group, positive control group, low dose grou, middle dose group and high dose group. CIA rats were induced by type Ⅱ collagen emulsion in each group, except the blank control group. After the establishment of the model, the rats in the low (2 mg/kg), middle (6 mg/kg) and high (54 mg/kg) dose groups were treated with ursolic acid, the positive control group was given hydroxychloroquine (36 mg/kg), and the blank group and model group were given 5 ml distilled water. All rats were given the drug once a day for 28 days. Two hours after the last intragastric administration, the specimens were extracted, and the joint index score, swelling degree and autophagy were observed under transmission electron microscope. The serum concentrations of HMGB1, TNF-α, IL-1 and INF-γ were detected by ELISA, and the protein expressions of HMGB1, Beclin1, Bcl-2 and PI3K were detected by PCR and WB.Results The levels of serum HMGB1, TNF-α, IL-1 and INF-γ in the model control group were higher than those in the blank control group, the levels of HMGB1, Bcl-2 and PI3 K protein in synovial tissue were higher than those in the blank control group, and the expression of Beclin1 protein was lower than that in the blank control group, the difference was statistically significant (P<0.05). The levels of HMGB1, TNF-α, IL-1, INF-γ, Bcl-2 and PI3K in the middle and high dose groups of usnic acid and the positive control group were lower than those in the model control group, and the expression of Beclin1 protein was higher than that in the model control group, the differences were statistically significant (P<0.05). There was no significant difference in the effect of inhibiting the expression of HMGB1, Bcl-2, PI3 K and activating Beclin1 between the middle, high dose groups of usnic acid and the positive control group (P>0.05).Conclusion Ursolic acid can reduce the degree of joint swelling in CIA rats, decrease the concentration of serum HMGB1, TNF-α, IL-1 and INF- γ, inhibit the expression of HMGB1, Bcl-2 and PI3K protein, increase the expression of Beclin1, enhance autophagy and reduce synovial inflammation.

参考文献/References:

[1]Alsousi AA,Igwe OJ.Redox-active trace metal-induced release of high mobility group box 1(HMGB1) and inflammatory cytokines in fibroblast-like synovial cells is Toll-like receptor 4 (TLR4) dependent[J].Biochim Biophys Acta Mol Basis Dis,2018,1864(11):3847-3858.[2]安阳,陆道敏,马武开,等.松筋通络方对胶原性关节炎大鼠血清IL-1、IL-1β、TNF-α及滑膜病理的影响[J].风湿病与关节炎,2013(11):32-34.[3]Postigo J,Iglesias M,Cerezo-Wallis D,et al.Mice deficient in CD38 develop an attenuated form of collagen type II-induced arthritis[J].PLoS One,2012,7(3):e33534.[4]熊国林,黄海潇,谢玲,等.类风湿性关节炎大鼠模型的制备[J].解放军医学杂志,2007(2):121-123.[5]郑学彬,龙淑会,李富杰,等.老年慢性牙周炎合并冠心病患者龈沟液及血清中IL-1β、TNF-α、IL-18及IFN-γ的表达与临床意义[J].中国老年学杂志,2020,40(11):2360-2363.[6]丁非凡,王朝燕.AD患者血清中炎症因子IL-6、IL-1β、TNF-α、IFN-γ水平变化情况及意义分析[J].湖南师范大学学报(医学版),2019,16(4):57-60.[7]Wang LH,Wu MH,Chen PC,et al.Prognostic significance of high-mobility group box protein 1 genetic polymorphisms in rheumatoid arthritis disease outcome[J].Int J Med Sci,2017,14(13):1382-1388.[8]Chen X,Chen C,Fan S,et al.Omega-3 polyunsaturated fatty acid attenuates the inflammatory response by modulating microglia polarization through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway following experimental traumatic brain injury[J].J Neuroinflammation,2018,15(1):116.[9]Tang Y,Zhao X,Antoine D,et al.Regulation of Posttranslational Modifications of HMGB1 During Immune Responses[J].Antioxid Redox Signal,2016,24(12):620-634.[10]Zhu B,Zhu Q,Li N,et al.Association of serum asma high mobility group box 1 with autoimmune diseases: A systematic review and meta-analysis[J].Medicine (Baltimore),2018,97(29):e11531.[11]Li YB,Xu P,Xu K,et al.Methotrexate affects HMGB1 expression in rheumatoid arthritis, and the downregulation of HMGB1 prevents rheumatoid arthritis progression[J].Mol Cell Biochem,2016,420(1-2):161-170.[12]郭鑫,杨俊.Beclin1调控自噬、凋亡与炎症反应的分子机制[J].中国老年学杂志,2014,34(18):5289-5291.[13]Majdoul S,Cosette J,Seye AK,et al.Peptides derived from evolutionarily conserved domains in Beclin-1 and Beclin-2 enhance the entry of lentiviral vectors into human cells[J].J Biol Chem,2017,292(45):18672-18681.[14]Mou K,Liu W,Han D,et al.HMGB1/RAGE axis promotes autophagy and protects keratinocytes from ultraviolet radiation-induced cell death[J].J Dermatol Sci,2017,85(3):162-169.[15]安阳,黄颖,曹跃朋,等.侗族药松杖方对类风湿关节炎患者活动期的临床疗效观察[J].贵阳中医学院学报,2018,40(1):87-89.[16]安阳,马武开,陆道敏,等.松筋通络方对胶原性关节炎大鼠关节炎症及滑膜细胞NF-κB信号的影响[J].医学信息,2013,26(29):77-78.

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更新日期/Last Update: 1900-01-01