Improvement effect and mechanism of paeoniflorin on glucose metabolism， inflammation and oxidative stress in rats with gestational diabetes mellitus

LIU Guiying; NIU Li; CHANG Xueyun; ZHOU Xiuyun

doi:10.6039/j.issn.1001-0408.2024.12.11

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Improvement effect and mechanism of paeoniflorin on glucose metabolism， inflammation and oxidative stress in rats with gestational diabetes mellitus

更新时间：2024-06-25

- Improvement effect and mechanism of paeoniflorin on glucose metabolism， inflammation and oxidative stress in rats with gestational diabetes mellitus
- ZHONGGUO YAOFANG Vol. 35, Issue 12, Pages: 1476-1481(2024)
- 作者机构：
  
  阜阳市妇女儿童医院产科，安徽阜阳　236000
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.12.11
  CLC： R965
- Published：30 June 2024，
  
  Received：21 November 2023，
  
  Revised：09 May 2024，
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刘桂英,牛丽,常雪允等.芍药苷对妊娠期糖尿病大鼠糖代谢、炎症、氧化应激的改善作用及机制 ^Δ[J].中国药房,2024,35(12):1476-1481.

LIU Guiying,NIU Li,CHANG Xueyun,et al.Improvement effect and mechanism of paeoniflorin on glucose metabolism， inflammation and oxidative stress in rats with gestational diabetes mellitus[J].ZHONGGUO YAOFANG,2024,35(12):1476-1481.
刘桂英,牛丽,常雪允等.芍药苷对妊娠期糖尿病大鼠糖代谢、炎症、氧化应激的改善作用及机制 ^Δ[J].中国药房,2024,35(12):1476-1481. DOI： 10.6039/j.issn.1001-0408.2024.12.11.

LIU Guiying,NIU Li,CHANG Xueyun,et al.Improvement effect and mechanism of paeoniflorin on glucose metabolism， inflammation and oxidative stress in rats with gestational diabetes mellitus[J].ZHONGGUO YAOFANG,2024,35(12):1476-1481. DOI： 10.6039/j.issn.1001-0408.2024.12.11.

摘要

目的

基于核转录因子红系2相关因子2（Nrf2）/血红素加氧酶1（HO-1）/依赖还原型辅酶/醌氧化还原酶1（NQO1）信号通路探究芍药苷对妊娠期糖尿病（GDM）大鼠糖代谢、炎症、氧化应激的改善作用及潜在机制。

方法

将以高脂高糖饲料喂养的雌性大鼠和以普通饲料喂养的雄性大鼠合笼，收集妊娠期大鼠，单次腹腔注射链脲佐菌素复制GDM模型。将造模成功的大鼠随机分为模型组，盐酸二甲双胍组（灌胃200 mg/kg盐酸二甲双胍），芍药苷低、高剂量组（分别灌胃45、90 mg/kg芍药苷），芍药苷+ML385组（灌胃90 mg/kg芍药苷并腹腔注射30 mg/kg Nrf2抑制剂ML385），每组12只；另取以普通饲料喂养的妊娠期大鼠12只，作为对照组。各组大鼠给予相应药物/生理盐水，每天1次，连续干预2周。检测其糖代谢指标[空腹血糖（FBG）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）]、血清炎症因子[白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）]和肾组织氧化应激指标[超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）]水平，观察肾组织病理变化，并检测肾组织中Nrf2、HO-1、NQO1蛋白的表达情况。

结果

与对照组相比，模型组大鼠肾组织病变明显，可见肾小球萎缩、肾小管上皮细胞水肿变性和大量炎症细胞浸润；FBG、FINS水平，HOMA-IR，血清IL-6、TNF-α水平，以及肾组织中MDA水平均显著升高（

＜0.05）；肾组织中SOD、GSH-Px水平和Nrf2、HO-1、NQO1蛋白的表达水平均显著降低（

＜0.05）。与模型组相比，芍药苷低、高剂量组大鼠肾组织病变有所减轻，上述各定量指标均显著改善，且芍药苷高剂量组的改善效果更优（

＜0.05）；ML385可显著逆转芍药苷对上述指标的改善作用（

＜0.05）。

结论

芍药苷可改善GDM大鼠的糖代谢异常、炎症和肾组织氧化应激损伤，上述作用可能与激活Nrf2/HO-1/NOQ1信号通路有关。

Abstract

OBJECTIVE

To explore the effect of paeoniflorin on glucose metabolism， inflammation and oxidative stress in rats with gestational diabetes mellitus （GDM） and its potential mechanism based on nuclear factor-erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/nicotinamide adenine dinucleotide phosphate：quinone oxidoreductase 1 （NQO1） signaling pathway.

METHODS

The female rats fed with high fat and high sugar diet and the male rats fed with an ordinary diet were caged， the successfully conceived rats were collected， and streptozotocin was injected intraperitoneally once to induce the GDM model. The successfully modeled rats were randomly divided into the model group， metformin hydrochloride group （200 mg/kg metformin by gavage）， paeoniflorin low-， high-dose groups （45， 90 mg/kg paeoniflorin by gavage， respectively）， paeoniflorin+ML385 group （90 mg/kg paeoniflorin by gavage and intraperitoneal injection of 30 mg/kg Nrf2 inhibitor ML385）， with 12 rats in each group； in addition， another 12 conceived rats fed with an ordinary diet were selected as the control group. The rats in each drug group were given the corresponding drug/normal saline， once a day， for 2 consecutive weeks. Glucose metabolism indexes [fasting blood glucose （FBG）， fasting insulin （FINS）， insulin resistance index （HOMA-IR）]， serum inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）] and renal tissue oxidative stress indexes [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）] were detected； the pathological changes of renal tissue were observed， and the protein expressions of Nrf2， HO-1 and NQO1 in renal tissue were detected.

RESULTS

Compared with the control group， the renal tissue lesions of the model group were obvious， including glomerular atrophy， edema degeneration of renal tubular epithelial cells and a large number of inflammatory cell infiltration； the levels of FBG and FINS， HOMA-IR， the levels of IL-6 and TNF-α in serum， and the level of MDA in renal tissue were significantly increased （

＜0.05）， while the levels of SOD and GSH-Px and the protein expressions of Nrf2， HO-1 and NQO1 in renal tissue were significantly decreased （

＜0.05）. Compared with the model group， the renal tissue lesions of rats in paeoniflorin low-dose and high-dose groups were reduced， the above quantitative indexes were significantly improved， and the improvement effect was better in high-dose group （

＜0.05）， while ML385 could significantly reverse the improvement effect of paeoniflorin on the above indexes （

＜0.05）.

CONCLUSIONS

Paeoniflorin can improve the abnormal glucose metabolism， inflammation and oxidative stress damage of renal tissue in GDM rats， which may be related to the activation of Nrf2/HO-1/NOQ1 signaling pathway.

关键词

芍药苷妊娠期糖尿病炎症氧化应激Nrf2/HO-1/NQO-1信号通路

Keywords

gestational diabetes mellitusinflammationoxidative stressNrf2/HO-1/NQO-1 signaling pathway

references

THILAK S，RAJENDRA A，GANESH V. Association of obesity and insulin resistance to gestational diabetes mel-litus[J]. Bioinformation，2023，19（2）：211-214.

WANG P，MA H H，HOU X Z，et al. N-acetyl-L-cysteine ameliorates gestational diabetes mellitus by inhibiting oxidative stress[J]. Biotechnol Appl Biochem，2023，70（3）：1128-1136.

LIANG W J，FENG Y Y，YANG D M，et al. Oral probio-tics increased the proportion of Treg，Tfr，and Breg cells to inhibit the inflammatory response and impede gestational diabetes mellitus[J]. Mol Med，2023，29（1）：122.

LU Q，ZHANG Y，ZHAO C，et al. Copper induces oxidative stress and apoptosis of hippocampal neuron via pCREB/BDNF and Nrf2/HO-1/NQO1 pathway[J]. J Appl Toxicol，2022，42（4）：694-705.

王丽. 妊娠期糖尿病患者胎盘组织Nrf2/HO-1通路表达及其意义[J]. 中国医学创新，2022，19（34）：155-158.

WANG L. Expression and significance of Nrf2/HO-1 pathway in placenta of gestational diabetes mellitus[J]. Med Innov China，2022，19（34）：155-158.

赵洪霄，李英，张金颖，等. 芍药苷对糖尿病肾病模型大鼠肾脏的保护作用及作用机制[J]. 中国药业，2022，31（3）：31-35.

ZHAO H X，LI Y，ZHANG J Y，et al. Protective effect and mechanism of paeoniflorin on kidney of diabetic nephropathy rats[J]. China Pharm，2022，31（3）：31-35.

SIMMONS D，IMMANUEL J，HAGUE W M，et al. Treatment of gestational diabetes mellitus diagnosed early in pregnancy[J]. N Engl J Med，2023，388（23）：2132-2144.

许梦丽，徐琼，崔翠，等. 灵芝多糖对妊娠期糖尿病大鼠肝脏损伤的保护作用[J]. 中国临床药理学杂志，2020，36（20）：3242-3245.

XU M L，XU Q，CUI C，et al. Protective effect of Ganoderma lucidum polysaccharides on liver injury[J]. Chin J Clin Pharmacol，2020，36（20）：3242-3245.

聂晓霞，王翠香. 葛根素提取物改善妊娠期糖尿病大鼠的氧化应激损伤[J]. 现代食品科技，2021，37（2）：44-48，63.

NIE X X，WANG C X. Puerarin improves oxidative stress in rats with gestational diabetes mellitus[J]. Mod Food Sci Technol，2021，37（2）：44-48，63.

李姗姗，田春雨，张国伟，等. 芍药苷对2型糖尿病模型大鼠心肌损伤的改善作用及机制研究[J]. 中国药房，2021，32（23）：2846-2853.

LI S S，TIAN C Y，ZHANG G W，et al. Study on improvement effects and mechanism of paeoniflorin on myocardial injury in type 2 diabetic model rats[J]. China Pharm，2021，32（23）：2846-2853.

凌林，佟晶，曾良. 芍药苷通过激活Nrf2/Keap1信号通路改善脓毒症急性肺损伤的研究[J]. 四川大学学报（医学版），2020，51（5）：664-669.

LING L，TONG J，ZENG L. Paeoniflorin improves acute lung injury in sepsis by activating Nrf2/Keap1 signaling pathway[J]. J Sichuan Univ Med Sci Ed，2020，51（5）：664-669.

杨娜，肖颖，刘静云. 茯苓多糖调控SIRT1/FOXO3a通路对妊娠糖尿病大鼠胰岛素抵抗的影响[J]. 中国优生与遗传杂志，2022，30（8）：1371-1375.

YANG N，XIAO Y，LIU J Y. Impact of Poria polysaccharides on insulin resistance in gestational diabetic rats by regulating SIRT1/FOXO3a pathway[J]. Chin J Birth Health Hered，2022，30（8）：1371-1375.

ZHENG F，WANG Y Z，WU Y X，et al. Effect of stabilization malvids anthocyanins on the gut microbiota in mice with oxidative stress[J]. J Food Biochem，2021，45（12）：4892-4902.

GUO T W，PAN Y，YANG L，et al. Flavonoid compound from Agrimonia pilosa Ledeb improves adipose insulin resistance by alleviating oxidative stress and inflammation[J]. BMC Complement Med Ther，2023，23（1）：322.

G BARDALLO R，PANISELLO-ROSELLÓ A，SANCHEZ-NUNO S，et al. Nrf2 and oxidative stress in liver ischemia/reperfusion injury[J]. FEBS J，2022，289（18）：5463-5479.

TAWFIK M K，MAKARY S，KESHAWY M M. Upregulation of antioxidant nuclear factor erythroid 2-related factor 2 and its dependent genes associated with enhancing renal ischemic preconditioning renoprotection using levosimendan and cilostazol in an ischemia/reperfusion rat model[J]. Arch Med Sci，2021，17（6）：1783-1796.

HUANG F，WANG X，XIAO G F，et al. Loganin exerts a protective effect on ischemia-reperfusion-induced acute kidney injury by regulating JAK2/STAT3 and Nrf2/HO-1 signaling pathways[J]. Drug Dev Res，2022，83（1）：150-157.

张育贵，张淑娟，边甜甜，等. 芍药苷药理作用研究新进展[J]. 中草药，2019，50（15）：3735-3740.

ZHANG Y G，ZHANG S J，BIAN T T，et al. New pro-gress in pharmacological action of paeoniflorin[J]. Chin Tradit Herb Drugs，2019，50（15）：3735-3740.

李新玉，邵云侠，王坤，等. 芍药苷减轻糖尿病小鼠肾组织炎症与JAK2/STAT3信号通路的关系[J]. 安徽医科大学学报，2018，53（7）：1026-1032.

LI X Y，SHAO Y X，WANG K，et al. Effect of paeoniflorin on preventing inflammation in diabetic mice kidneys and its relationship with JAK2/STAT3 signaling pathway[J]. Acta Univ Med Anhui，2018，53（7）：1026-1032.

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