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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

29卷

期数:

2023年04期

页码:

398-405

栏目:

基础医学

出版日期:

2023-07-10

文章信息/Info

Title:

Effect of ginsenoside Rg1 on inhibition of NLRP3/Caspase-1 pathway against renal fibrosis

文章编号:

1006-8147（2023）04-0398-08

作者:

滕杰; 陈业刚

天津医科大学第二医院泌尿外科，天津300211

Author(s):

TENG Jie; CHEN Ye-gang

Department of Urology，The Second Hospital，Tianjin Medical University，Tianjin 300211，China

关键词:

肾纤维化; 人参皂苷Rg1; 细胞焦亡; NLRP3; Caspase-1

Keywords:

renal fibrosis; ginsenoside Rg1; pyroptosis; NLRP3; caspase-1

分类号:

R692

DOI:

-

文献标志码:

A

摘要:

目的：通过体内外实验探讨人参皂苷Rg1对转化生长因子-β1（TGF-β1）诱导的人肾小管上皮细胞HK2纤维化细胞株中炎症及其抗纤维化的机制。方法：将HK2细胞诱导分组为对照组、纤维化模型组（2ng/mL的TGF-β1诱导纤维化）、低剂量人参皂苷Rg1治疗组（2ng/mL的TGF-β1+15μg/mL人参皂苷Rg1）、高剂量人参皂苷Rg1治疗组（2ng/mL的TGF-β1+45μg/mL人参皂苷Rg1）；Western印迹及免疫荧光检测结缔组织生长因子（CTGF）、α-平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原蛋白（Col-1）表达水平；Western印迹检测NOD样受体蛋白3（NLRP3）及半胱氨酸天冬氨酸蛋白水解酶-1（Caspase-1）表达水平；透射电镜检测细胞焦亡水平。动物研究将大鼠诱导分为对照组、模型组（单侧输尿管梗阻）、低剂量人参皂苷Rg1治疗组（单侧输尿管梗阻大鼠+50mg/kg人参皂苷Rg1）、高剂量人参皂苷Rg1治疗组（单侧输尿管梗阻大鼠+100mg/kg人参皂苷Rg1）；Western印迹检测肾组织中蛋白表达水平；苏木精-伊红（HE）及Masson检测肾脏病理改变及纤维化程度；酶联免疫吸附测定法（ELISA）检测血清中炎症因子表达水平；透射电镜检测组织焦亡水平。结果：细胞实验中，人参皂苷Rg1处理后，细胞中CTGF、α-SMA、ColⅠ及NLRP3、Caspase-1的表达水平均较模型组以剂量依赖的减低（均P<0.05）；细胞焦亡水平显著降低。动物实验中，人参皂苷Rg1处理后，大鼠肾组织中CTGF、α-SMA、ColⅠ及NLRP3、Caspase-1的表达水平均较模型组以剂量依赖的减低（均P<0.05）；血清TGF-β1、白细胞介素-18（IL-18）、白细胞介素-1β（IL-1β）呈剂量依赖的显著下降（均P<0.05）；大鼠肾脏病理改变减轻，胶原沉积减少；组织焦亡水平显著降低。结论：人参皂苷Rg1可以通过抑制NLRP3/Caspase-1通路抑制肾小管上皮细胞焦亡，进而降低CTGF、α-SMA、CollagenⅠ的表达，从而实现对肾脏的保护作用。

Abstract:

Objective：To investigate the mechanism of ginsenoside Rg1 on inflammatory response and anti-fibrosis in human renal tubular epithelial cell line HK2 fibrotic induced by transforming growth factor-β1（ TGF-β 1） in vivo and in vitro. Methods：HK2 cells were grouped into control group，fibrosis model group（ 2 ng/mL of TGF-β1 induced fibrosis），low-dose ginsenoside Rg1 treatment group （ 2 ng/mL of TGF-β1+15 μg/mL ginsenoside Rg1），and high-dose ginsenoside Rg1 treatment group（ 2 ng/mL of TGF-β1+45 μg/mL ginsenoside Rg1）. Western blotting and immunofluorescence were used to detect the expression of connective tissue growth factor （ CTGF），α-smooth muscle actin（ α-SMA）and collagen I（ Col-1）. Western blotting was used to detect the expression of Nod-like receptor protein3（ NLRP3） and caspase-1. The level of cellular pyroptosis was detected by transmission electron microscopy . Rats were devided into control group，model group （ unilateral ureteral obstruction），low-dose ginsenoside Rg1 treatment group（ unilateral ureteral obstruction rats+50 mg/kg ginsenoside Rg1），and high-dose ginsenoside Rg1 treatment group（ unilateral ureteral obstruction rats+100 mg/kg ginsenoside Rg1）in animal studies. Enzyme-linked immunosorbent assay（ ELISA） was used to detect the expression level of inflammatory factors in serum. Hematoxylin-eosin staining（ HE） and Masson were used to detect renal pathological changes and the degree of fibrosis. Western blotting was used to detect the protein expression level in renal tissues. Transmission electron microscopy was used to detect the level of tissue pyroptosis. Results：In cellular experiments，the expression levels of CTGF，α-SMA，ColⅠ，NLRP3 and caspase-1 in cells were reduced in a dose-dependent manner after ginsenoside Rg1 treatment compared with the model group（ all P<0.05）; the level of cell pyroptosis was significantly reduced. In the animal test，the expression levels of CTGF，α-SMA，ColⅠ， NLRP3 and caspase-1 in the kidney tissues of rats after ginsenoside Rg1 treatment were reduced in a dose-dependent manner compared with the model group（ all P<0.05）；the expression levels of TGF-β1，interleukin-18（ IL-18） and interleukin-1β（ IL-1β） in the serum were reduced in a dose-dependent manner （ all P<0.05）；the pathological changes in rat kidney were alleviated and collagen deposition was reduced; the level of tissue pyroptosis decreased significantly. Conclusion：Ginsenoside Rg1 can inhibit renal tubular ep－ithelial cell pyroptosis by inhibiting NLRP3/Caspase-1 pathway，and reduce the expression of CTGF，α-SMA and ColⅠ，thus achieving a protective effect on the kidney.

参考文献/References:

[1] ALLINOVI M，DE CHIARA L，ANGELOTTI M L，et al. Anti-fibrot－ic treatments：a review of clinical evidence[J]. Matrix Biol，2018， 68-69：333-354.
[2] 刘紫琦，杜玄一.细胞焦亡在急性肾损伤中的研究进展[J].中国血液净化，2021，20（ 11）：762-765.
[3] LV W S，BOOZ G W，WANG Y G，et al. Inflammation and renal fi－brosis：recent developments on key signaling molecules as potential therapeutic targets[J]. Eur J Pharmacol，2018，820：65-76.
[4] 吴胜斌，王应灯.人参皂苷Rg1对肾间质纤维化大鼠肾组 织 肝细胞生长因子及转化生长因子-β1的影响[J].中华实用诊断与治疗杂志，2019，33（ 5）：422-425.
[5] WU J，SAOVIENG S，CHENG I S，et al. Ginsenoside Rg1 supple－mentation clears senescence-associated β-galactosidase in exercis－ing human skeletal muscle[J]. J Ginseng Res，2019，43（4）：580-588.
[6] LI Y，ZHANG D D，LI L，et al. Ginsenoside Rg1 ameliorates aginginduced liver fibrosis by inhibiting the NOX4/NLRP3 inflammasome in SAMP8 mice[J]. Mol Med Rep，2021，24（ 5）：801.
[7] 庄子锐，王明亮，张婷，等.肝肾纤维化动物模 型 的研究进展及评价[J].中国实验动物学报，2020，28（ 6）：845-852.
[8] HUMPHREYS B D. Mechanisms of renal fibrosis[J]. Annu Rev Physi－ol，2018，80：309-326.
[9] DUAN L，XIONG X J，HU J Y，et al. Panax notoginseng saponins for treating coronary artery disease：a functional and mechanistic overview[J]. Front Pharmacol，2017，8：702.
[10] MANCUSO C，SANTANGELO R. Panax ginseng and panax quinque－folius：from pharmacology to toxicology[J]. Food Chem Toxicol，2017， 107（ PtA）：362-372.
[11] XU Z M，LI C B，LIU Q L，et al. Ginsenoside Rg1 prevents doxoru－bicin-induced cardiotoxicity through the inhibition of autophagy and endoplasmic reticulum stress in mice[J]. Int J Mol Sci，2018，19（11）：E3658.
[12] GUAN S B，LIU Q，HAN F F，et al. Ginsenoside Rg1 ameliorates cigarette smoke-induced airway fibrosis by suppressing the TGF-β1/smad pathway in vivo and in vitro[J]. Biomed Res Int，2017， 2017：6510198.
[13] XIE X S，LIU H C，YANG M，et al. Ginsenoside Rb1，a panoxadiol saponin against oxidative damage and renal interstitial fibrosis in rats with unilateral ureteral obstruction[J]. Chin J Integr Med，2009， 15（ 2）：133-140.
[14] TANG，G，LI，S，ZHANG C，et al. Clinical efficacies，underlying mech－anisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management[J]. Acta Pharm Sin B，2021， 11（ 9）：2749-2767.
[15] 王悦彤，徐薇，李现成，等.益血降浊汤对 TGF-β1诱导的肾小管上皮细 胞 α-SMA表达的影响[J].云南中医中药杂志，2019，40 （10）：68-72.
[16] 孙晓怡，姜玉勤，唐余燕，等.细胞焦亡机制及其在多种肾脏病中的作用[J].中国医药导报，2021，18（ 33）：53-56.
[17] KELLEY N，JELTEMA，D，DUAN，Y，et al. The NLRP3 inflamma－some：an overview of mechanisms of activation and regulation [J]. Int J Mol Sci，2019，20（ 13）：3328.
[18] 阚晨静.基 于细 胞 焦亡NLRP3/Caspase-1通路探究人参皂苷Rg1对心肌纤维化的作用机制[D].南京中医药大学，2022.
[19] 龙俊鹏，孙洋，刘莎莎，等.人参皂苷Rg1的神经保护作用研究进展[J].药学学报，2023，1：14.
[20] 李彬，张大传，李学望，等.人参皂苷Rg1抑制NLRP3炎症小体对 2型 糖尿病小鼠视网膜病变的保护作用[J].中国中药杂志， 2022，47（ 2）：476-483.

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[1]徐娜,帅一尘,王超坤,等.扶肾降浊方通过调控自噬与凋亡改善肾纤维化的作用机制研究[J].天津医科大学学报,2026,32(01):49.[doi:10.20135/j.issn.1006-8147.2026.01.0049]
　XU Na,SHUAI Yichen,WANG Chaokun,et al.Study on the mechanism of Fushen Jiangzhuo Formula in improving renal fibrosis by regulating autophagy and apoptosis[J].Journal of Tianjin Medical University,2026,32(04):49.[doi:10.20135/j.issn.1006-8147.2026.01.0049]

备注/Memo

备注/Memo:

基金项目: 天津市卫健委中医课题一般项目（2021171）
作者简介: 滕杰（1993-），男，硕士在读，研究方向：泌尿外科疾病；
通信作者：陈业刚，E-mail：18822349806@163.com。

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更新日期/Last Update: 2023-07-10