Effects and mechanism of limonin on renal lesion， glucose metabolism， inflammation and oxidative stress in gestational diabetic rats

QU Na; ZHANG Kai; NA Lisha; CUI Ying

doi:10.6039/j.issn.1001-0408.2025.09.11

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Effects and mechanism of limonin on renal lesion， glucose metabolism， inflammation and oxidative stress in gestational diabetic rats

更新时间：2025-09-23

- Effects and mechanism of limonin on renal lesion， glucose metabolism， inflammation and oxidative stress in gestational diabetic rats
- ZHONGGUO YAOFANG Vol. 36, Issue 9, Pages: 1082-1086(2025)
- 作者机构：
  
  1.牡丹江医科大学附属红旗医院药学部，黑龙江牡丹江　157000
  2.牡丹江医科大学附属红旗医院妇产科，黑龙江牡丹江　157000
  3.牡丹江医科大学第一临床医学院，黑龙江牡丹江　157000
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.09.11
  CLC： R285;R965
- Received：05 February 2025，
  
  Revised：2025-03-20，
  
  Accepted：20 March 2025，
  
  Published：15 May 2025
- 稿件说明：
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曲娜,张凯,那丽莎,等.柠檬苦素对妊娠期糖尿病大鼠肾脏病变及糖代谢、炎症和氧化应激的影响及机制 [J].中国药房,2025,36(09):1082-1086.

QU Na,ZHANG Kai,NA Lisha,et al.Effects and mechanism of limonin on renal lesion， glucose metabolism， inflammation and oxidative stress in gestational diabetic rats[J].ZHONGGUO YAOFANG,2025,36(09):1082-1086.
曲娜,张凯,那丽莎,等.柠檬苦素对妊娠期糖尿病大鼠肾脏病变及糖代谢、炎症和氧化应激的影响及机制 [J].中国药房,2025,36(09):1082-1086. DOI： 10.6039/j.issn.1001-0408.2025.09.11.

QU Na,ZHANG Kai,NA Lisha,et al.Effects and mechanism of limonin on renal lesion， glucose metabolism， inflammation and oxidative stress in gestational diabetic rats[J].ZHONGGUO YAOFANG,2025,36(09):1082-1086. DOI： 10.6039/j.issn.1001-0408.2025.09.11.

摘要

目的

探究柠檬苦素对妊娠期糖尿病大鼠肾脏病变及糖代谢、炎症、氧化应激的影响及可能机制。

方法

采用腹腔注射链脲佐菌素法构建妊娠期糖尿病大鼠模型。将妊娠大鼠分为模型组（灌胃并尾静脉注射等体积生理盐水），柠檬苦素低、中、高剂量组（灌胃12.5、25.0、50.0 mg/kg柠檬苦素并尾静脉注射等体积生理盐水），联合组[灌胃50.0 mg/kg柠檬苦素+尾静脉注射2 mg/kg c-Jun氨基端激酶（JNK）激活剂Anisomycin]，每组12只；另取12只妊娠大鼠作为对照组（灌胃并尾静脉注射等体积生理盐水）；每天1次，连续14 d。末次给药后，检测空腹血糖（FBG）值，检测血清中空腹胰岛素（FINS）、白细胞介素1β（IL-1β）、IL-6、肿瘤坏死因子α（TNF-α）水平，检测肾组织中超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）、血尿素氮（BUN）、肌酐（Cr）水平，观察肾组织病理变化，检测肾组织中JNK/核因子κB（NF-κB）信号通路相关蛋白的表达。

结果

与对照组比较，模型组大鼠肾组织出现肾小球萎缩、肾小管上皮细胞水肿等病理损伤；FBG、FINS、IL-1β、IL-6、TNF-α、MDA、BUN、Cr水平，HOMA-IR和JNK、NF-κB p65蛋白的磷酸化水平均显著升高（

＜0.05）；SOD、GSH-Px水平均显著降低（

＜0.05）。与模型组比较，柠檬苦素各剂量组大鼠肾组织病变程度均减轻，上述指标均显著改善（

＜0.05），且存在明显的量效关系（

＜0.05）。与柠檬苦素高剂量组比较，联合组大鼠肾组织病变程度相对加重，上述指标变化被显著逆转（

＜0.05）。

结论

柠檬苦素对妊娠期糖尿病大鼠肾脏病变及糖代谢、炎症、氧化应激具有一定的改善作用，其机制可能与抑制JNK/NF-κB信号通路有关。

Abstract

OBJECTIVE

To explore the effects of limonin on renal lesions， glucose metabolism， inflammation， and oxidative stress in gestational diabetic rats and its possible mechanisms.

METHODS

The model of gestational diabetic rats was established by intraperitoneal injection of streptozotocin. The diabetic rats were divided into the model group （intragastrical administration and tail vein injection of equal volume of normal saline）， limonin low-， medium-， and high-dose groups （intragastrical administration of limonin， at doses of 12.5， 25.0 and 50.0 mg/kg， and equal volume of normal saline into the tail vein）， and combination group [intragastrical administration of limonin 50.0 mg/kg + tail vein injection of c-Jun

-terminal kinase （JNK） activator Anisomycin 2 mg/kg

]

， with 12 rats in each group. In addition， 12 pregnant rats were selected as the control group （intragastrical administration and tail vein injection of equal volume of normal saline）. They were given relevant medicine， once a day， for 14 consecutive days. After the last administration， fasting blood glucose （FBG）， the levels of fasting insulin （FINS）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） in the serum were detected； the lev

els of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， blood urea nitrogen （BUN）， and creatinine （Cr） in the renal tissue were detected； the pathological changes of renal tissue were observed； the expressions of proteins related to the JNK/nuclear factor-κB （NF-κB） signaling pathway in the renal tissue were detected.

RESULTS

Compared with control group， in model group， the rats showed pathological injuries in the kidney tissue， such as glomerular atrophy， edema of renal tubular epithelial cells； the levels of FBG， FINS， IL-1β， IL-6， TNF-α， MDA， BUN and Cr， HOMA-IR， as well as the phosphorylation levels of JNK and NF-κB p65 proteins were increased significantly （

＜0.05）， while the levels of SOD and GSH-Px were decreased significantly （

＜0.05）. Compared with model group， in each dose group of limonin， the degree of renal tissue lesions in rats was alleviated， and the above-mentioned indicators were significantly improved （

＜0.05）， showing an obvious dose-effect relationship （

＜0.05）. Compared with high-dose limonin group， in the combination group， the degree of renal tissue lesions in rats was relatively aggravated， and the changes in the above-mentioned indicators were significantly reversed （

＜0.05）.

CONCLUSIONS

Limonin has a certain improvement effect on renal lesions， glucose metabolism， inflammation， and oxidative stress in pregnant rats with gestational diabetes. Its mechanism may be related to the inhibition of the JNK/NF-κB signaling pathway.

关键词

Keywords

references

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