松果菊苷对尿毒症大鼠肾损伤的影响及机制

熊玮; 彭斌; 高智

doi:10.6039/j.issn.1001-0408.2024.02.13

您当前的位置：

首页 >

文章列表页 >

松果菊苷对尿毒症大鼠肾损伤的影响及机制

药学研究 | 更新时间：2024-01-24

- 松果菊苷对尿毒症大鼠肾损伤的影响及机制
- Effects of echinacoside on renal injury in uremia rats and its mechanism
- 中国药房 2024年35卷第2期页码：198-203
- 作者机构：
  
  武汉市中医医院肾病科，武汉　430014
- 作者简介：
  
  主治医师，硕士。研究方向：中西医结合治疗肾脏病。E-mail：xw1980x@163.com
- 基金信息：
  
  武汉市医学科研项目(WZ20C16)
- DOI：10.6039/j.issn.1001-0408.2024.02.13
  中图分类号： R965;R285
- 纸质出版日期：2024-01-30，
  
  收稿日期：2023-07-21，
  
  修回日期：2023-12-29，
扫描看全文
熊玮,彭斌,高智.松果菊苷对尿毒症大鼠肾损伤的影响及机制 ^Δ[J].中国药房,2024,35(02):198-203.

XIONG Wei,PENG Bin,GAO Zhi.Effects of echinacoside on renal injury in uremia rats and its mechanism[J].ZHONGGUO YAOFANG,2024,35(02):198-203.
熊玮,彭斌,高智.松果菊苷对尿毒症大鼠肾损伤的影响及机制 ^Δ[J].中国药房,2024,35(02):198-203. DOI： 10.6039/j.issn.1001-0408.2024.02.13.

XIONG Wei,PENG Bin,GAO Zhi.Effects of echinacoside on renal injury in uremia rats and its mechanism[J].ZHONGGUO YAOFANG,2024,35(02):198-203. DOI： 10.6039/j.issn.1001-0408.2024.02.13.

摘要

目的

研究松果菊苷（ECH）对尿毒症（URE）大鼠肾损伤的影响及机制。

方法

采用5/6肾切除法建立URE大鼠模型。建模成功的大鼠分为尿毒症（URE）组、ECH低剂量[10 mg/（kg·d）]组、ECH中剂量组[20 mg/（kg·d）]、ECH高剂量组[40 mg/（kg·d）]和ECH高剂量+茴香霉素[p38丝裂原活化蛋白激酶（p38 MAPK）信号通路激活剂]组[ECH-H+Ani组，40 mg/（kg·d）ECH+2 mg/（kg·d）茴香霉素]，另设假手术组，每组12只。各药物组灌胃相应的ECH，ECH-H+Ani组再尾静脉注射茴香霉素，每天1次，连续给药8周。检测大鼠血清中肿瘤细胞因子α（TNF-α）、白细胞介素1β（IL-1β）、IL-6、血尿素氮（BUN）、β2-微球蛋白（β2-MG）、血肌酐（Scr）、中性粒细胞明胶酶相关载脂蛋白（NGAL）、肾损伤分子1（KIM-1）、胱抑素C（Cys-C）水平，24 h尿蛋白（24 h UP）和肾组织中丙二醛（MDA）水平、超氧化物歧化酶（SOD）活性；观察肾组织病理学变化；检测大鼠肾组织中α-平滑肌肌动蛋白（α-SMA）、E-上皮钙黏素（E-cadherin）阳性表达率和p38 MAPK、核因子κB（NF-κB）p65的磷酸化水平。

结果

与URE组相比，ECH各剂量组大鼠肾小球肿胀及上皮细胞损伤坏死明显减轻，炎症细胞浸润明显减少；肾损伤评分和TNF-α、IL-1β、IL-6、BUN、Scr、β2-MG、24 h UP、NGAL、KIM-1、Cys-C、MDA水平及α-SMA阳性表达率、p38 MAPK和NF-κB p65的磷酸化水平均呈剂量依赖性降低而SOD活性和E-cadherin阳性表达率均呈剂量依赖性升高（

＜0.05）。茴香霉素可显著逆转高剂量ECH对URE大鼠肾损伤及相关指标的改善作用（

＜0.05）。

结论

ECH可能通过抑制p38 MAPK/NF-κB信号通路激活来抑制URE大鼠的炎症反应和氧化应激反应，增强肾功能，改善肾损伤。

Abstract

OBJECTIVE

To investigate the effects of echinacoside （ECH） on renal injury in uremia （URE） rats and its mechanism.

METHODS

URE model of the rat was established by 5/6 nephrectomy. Successfully modeled rats were grouped into uremia group （URE group）， ECH low-dose [10 mg/（kg·d）] group， ECH medium-dose [20 mg/（kg·d）] group， ECH high-dose [40 mg/（kg·d）] group， ECH high-dose+anisomycin [p38 mitogen-activated protein kinase （p38 MAPK） pathway activator] group [ECH-H+Ani group， 40 mg/（kg·d） ECH +2 mg/（kg·d） anisomycin]， with a sham operation group， 12 mice in each group. Each drug group was given corresponding ECH intragastrically， while ECH-H+Ani group was further injected with anisomycin via the tail vein， once a day， for 8 consecutive weeks. The serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， blood urea nitrogen （BUN）， β2-microglobulin （β2-MG）， serum creatinine （Scr）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， cystatin C （Cys-C） and 24 h urine protein （24 h UP） as well as the levels of malondialdehyde （MDA） and superoxide dismutase （SOD） activity in renal tissue were all detected； pathological changes of renal tissue were observed； the rate of positive expression of α-smooth muscle protein （α-SMA） and E-cadherin， and the phosphorylation of p38 MAPK and nuclear factor-κB （NF-κB） p65 were determined in renal tissue of rats.

RESULTS

Compared with URE group， glomerular swelling， damage and necrosis of renal tubular epithelial cells and inflammatory cell infiltration were relieved significantly in ECH groups. The renal injury score， levels of TNF-α， IL-1β， IL-6， BUN， Scr， β2-MG， 24 h UP， NGAL， KIM-1， Cys-C and MDA， the positive expression rate of α-SMA in renal tissue， the phosphorylation of p38 MAPK and NF-κB p65 were decreased in dose-dependent manner， while SOD activity and the positive expression rate of E-cadherin were obviously increased in dose-dependent manner （

＜0.05）. Anisomycin significantly attenuated the improvement effect of high-dose ECH on renal injury in URE rats （

＜0.05）.

CONCLUSIONS

ECH may inhibit inflammation and oxidative stress， enhance renal function， and improve renal injury in uremic rats by inhibiting the activation of p38 MAPK/NF-κB signaling pathway.

关键词

松果菊苷尿毒症肾损伤p38丝裂原活化蛋白激酶/核因子κB信号通路

Keywords

uremiarenal injuryp38 mitogen-activated protein kinase/nuclear factor-κB signaling pathway

references

DING Y H，ZHANG Y，WANG Z H，et al. Echinacoside from Cistanche tubulosa ameliorates alcohol-induced liver injury and oxidative stress by targeting Nrf2[J]. FASEB J，2023，37（3）：e22792.

ZHAO Y D，YI Y，GU B，et al. Echinacoside protects adenine-induced uremic rats from sciatic nerve damage by up-regulating α-klotho[J]. J Musculoskelet Neuronal Inter-act，2021，21（3）：413-421.

米妍妍，徐曼，王春双. 松果菊苷通过IL-33/STAT轴对脓毒症大鼠急性肾损伤的保护作用及机制研究[J]. 西部医学，2023，35（4）：519-523，528.

MI Y Y，XU M，WANG C S. Effect and mechanism of echinacoside on acute kidney injury in septic rats through IL-33/STAT axis[J]. Med J West China，2023，35（4）：519-523，528.

高书涛. 松果菊苷抑制NF-κB/NLRP3信号通路减轻脊髓损伤的实验研究[D]. 乌鲁木齐：新疆医科大学，2020.

GAO S T. Alleviative effects of echinacoside against spinal cord injury via inhibiting NF-κB/NLRP3 signaling pathway[D]. Urumqi：Xinjiang Medical University，2020.

ZHANG H F，WANG Y L，GAO C，et al. Salvianolic acid A attenuates kidney injury and inflammation by inhibiting NF-κB and p38 MAPK signaling pathways in 5/6 nephrectomized rats[J]. Acta Pharmacol Sin，2018，39（12）：1855-1864.

LI X S，ZHENG J，WANG J，et al. Effects of uremic clea-rance granules on p38 MAPK/NF-κB signaling pathway，microbial and metabolic profiles in end-stage renal disease rats receiving peritoneal dialysis[J]. Drug Des Devel Ther，2022，16：2529-2544.

王晔，高宏宇，张莉，等. JNK/NF-κB通路在沙利度胺减轻膜性肾病大鼠足细胞损伤中的作用[J]. 中国中西医结合肾病杂志，2022，23（10）：910-912，946.

WANG Y，GAO H Y，ZHANG L，et al. The role of JNK/NF-κB pathway in thalidomide alleviating podocyte injury in rats with membranous nephropathy[J]. Chin J Integr Tradit West Nephrol，2022，23（10）：910-912，946.

SUN Z H，ZHENG W L，TENG J，et al. Resveratrol reduces kidney injury in a rat model of uremia and is asso-ciated with increased expression of heat shock protein 70（Hsp70）[J]. Med Sci Monit，2020，26：e919086.

RAFIEE Z，MOAIEDI M Z，GORJI A V，et al. P-cou-maric acid mitigates doxorubicin-induced nephrotoxicity through suppression of oxidative stress，inflammation and apoptosis[J]. Arch Med Res，2020，51（1）：32-40.

ZHU J F，ZHANG Y F，SHI L，et al. RP105 protects against ischemic and septic acute kidney injury via suppressing TLR4/NF-κB signaling pathways[J]. Int Immunopharmacol，2022，109：108904.

ZHANG L，SUN J，ZHANG M，et al. The significance of combined detection of CysC，urinary mAlb and β2-MG in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome[J]. Saudi J Biol Sci，2019，26（8）：1982-1985.

ŞEN S，ÖZALP KıZıLAY D，TANELI F，et al. Urinary NGAL is a potential biomarker for early renal injury in insulin resistant obese non-diabetic children[J]. J Clin Res Pediatr Endocrinol，2021，13（4）：400-407.

罗煜，吴嘉思，朱正文，等. 盐酸巴马汀抑制NF-κB/p38 MAPK信号通路及NLRP3炎症小体抗炎机制研究[J]. 中药新药与临床药理，2020，31（7）：762-768.

LUO Y，WU J S，ZHU Z W，et al. Anti-inflammatory effect of palmatine hydrochloride and its mechanism in regulation of NF-κB/p38 MAPK signaling pathway and NLRP3 inflammasome[J]. Tradit Chin Drug Res Clin Pharmacol，2020，31（7）：762-768.

董倩兰，张琳萍，闫晓辉，等. 肾衰宁胶囊对尿毒症贫血患者外周血Hb、TNF-α及NF-κB水平的影响[J]. 中国中西医结合肾病杂志，2020，21（3）：241-242.

DONG Q L，ZHANG L P，YAN X H，et al. Effect of Shenshuaining capsule on the levels of Hb，TNF-α and NF-κB in peripheral blood of patients with uremic anemia[J]. Chin J Integr Tradit West Nephrol，2020，21（3）：241-242.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

暂无数据