Effect of Tianhuang Formula on Renal Injury and Fibrosis in Hyperuricemia Mice

MO Juxian; WU Kaireng; LI Minghui; CHEN Zhe; LAN Tian; XIAO Wei; GUO Jiao

doi:10.13422/j.cnki.syfjx.20230511

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Effect of Tianhuang Formula on Renal Injury and Fibrosis in Hyperuricemia Mice

更新时间：2023-04-28

- Effect of Tianhuang Formula on Renal Injury and Fibrosis in Hyperuricemia Mice
  增强出版
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 11, Pages: 72-81(2023)
- 作者机构：
  
  1.广东药科大学中医药研究院，广东省代谢病中西医结合研究中心，糖脂代谢病教育部重点实验室，广东省代谢性疾病中医药防治重点实验室，广州 510006
  2.广东药科大学药学院，广州 510006
  3.广东药科大学中药学院，广州 510006
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230511
  CLC： R284;R285;R289;R287;R22;R2-031;R33;R24
- Published：05 June 2023，
  
  Published Online：21 March 2023，
  
  Received：23 November 2022，
- 稿件说明：
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莫菊鲜,吴铠礽,李明慧等.田黄方对高尿酸血症小鼠肾损伤及纤维化的作用[J].中国实验方剂学杂志,2023,29(11):72-81.

MO Juxian,WU Kaireng,LI Minghui,et al.Effect of Tianhuang Formula on Renal Injury and Fibrosis in Hyperuricemia Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(11):72-81.
莫菊鲜,吴铠礽,李明慧等.田黄方对高尿酸血症小鼠肾损伤及纤维化的作用[J].中国实验方剂学杂志,2023,29(11):72-81. DOI： 10.13422/j.cnki.syfjx.20230511.

MO Juxian,WU Kaireng,LI Minghui,et al.Effect of Tianhuang Formula on Renal Injury and Fibrosis in Hyperuricemia Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(11):72-81. DOI： 10.13422/j.cnki.syfjx.20230511.

摘要

目的

观察田黄方对高尿酸血症肾病（HN）小鼠肾损伤的保护作用，并通过网络药理学探讨其可能的作用机制。

方法

将所有小鼠随机分为5组，正常组、模型组、非布司他组、田黄方低、高剂量组。正常组小鼠每日灌胃0.5%羧甲基纤维素钠（CMC-Na），其余组小鼠灌胃500 mg·kg

-1

次黄嘌呤和腹腔注射200 mg·kg

-1

氧嗪酸钾诱导HN模型，非布司他组小鼠每日灌胃5 mg·kg

-1

非布司他，田黄方组小鼠每日灌胃60 mg·kg

-1

和120 mg·kg

-1

田黄方，连续给药3周。检测小鼠血清尿酸、肌酐、尿素氮水平和24 h尿蛋白含量；采用苏木素-伊红（HE）染色和过碘酸雪夫（PAS）染色观察肾脏损伤程度，采用天狼猩红染色观察肾脏纤维化情况；通过蛋白免疫印迹法（Western blot）、网络药理学及分子对接研究田黄方在HN小鼠中的作用及其分子机制。

结果

生化结果提示，与模型组比较，田黄方低剂量组BUN和24 h尿蛋白水平明显降低（

0.05），SUA、SCr水平显著降低（

0.01），田黄方高剂量组，SUA、BUN、SCr和24 h尿蛋白水平显著降低（

0.01）；病理染色结果表明田黄方各剂量组对肾脏损伤和间质纤维化有不同程度改善作用（

0.05）；Western blot结果表明田黄方高剂量组能够使NOD样受体热蛋白结构域相关蛋白3（NLRP3）炎性小体、白细胞介素-1

（IL-1

）、纤维黏连蛋白（FN）、及尿酸转运蛋白1（URAT1）、磷酸化p65（p-p65）和磷酸化核转录因子（NF）-

B抑制蛋白

（p-I

）的表达降低到正常水平（

0.01），而田黄方低剂量组不影响HN小鼠IL-1

、URAT1和p-I

的蛋白表达。

结论

田黄方通过抑制NF-

B和NLRP3炎性小体激活改善肾脏炎症和纤维化减轻HN。

Abstract

Objective

To observe the protective effect and mechanism of Tianhuang formula (THF) against renal injury in hyperuricemia nephropathy (HN) mice through network pharmacology.

Method

All mice were randomly divided into a normal group

a model group

a febuxostat group (5 mg·kg

-1

)

a low-dose THF group (L-THF

60 mg·kg

-1

)

and a high-dose THF group (H-THF

120 mg·kg

-1

). The mice in the normal group were treated with 0.5% sodium carboxymethylcellulose (CMC-Na) by gavage daily. The HN model was induced by oral administration of 500 mg·kg

-1

hypoxanthine and intraperitoneal injection of 200 mg·kg

-1

oteracil potassium in mice except for those in the blank group. The mice in the groups with drug intervention were treated with corresponding drugs by gavage for three weeks. The levels of serum uric acid

creatinine

urea nitrogen

and 24-h albuminuria were measured. The renal injury was observed by hematoxylin-eosin (HE) staining and PAS staining

and renal fibrosis was observed by Sirius red staining. The effects and molecular mechanism of THF in HN mice were analyzed by Western blot

network pharmacology

and molecular docking.

Result

Biochemical results indicated that compared with model group

BUN and 24 h urinary protein levels were significantly decreased in L-THF group (

0.05)

SUA and SCr levels were significantly decreased (

0.01)

and SUA

BUN

SCr and 24 h urinary protein levels in H-THF group were significantly decreased (

0.01). The results of pathological staining showed that the kidney injury and interstitial fibrosis were improved in different doses of THF groups (

0.05). Western blot results showed that the Nod-like receptor heat protein domain associated protein 3 (NLRP3) inflammatorome

interleukin-1

(IL-1

)

fibronectin (FN)

uric acid transporter 1 (URAT1)

phosphorylated p65 (p-p65) and phosphorylated nuclear transcription factor (NF) -

B were inhibited in the H-THF group The expression of protein-producing

(p-I

) was reduced to the normal level (

0.01)

but the expression of IL-1

URAT1 and p-I

in HN mice was not affected in the L-THF group.

Conclusion

THF ameliorates renal inflammation and fibrosis by inhibiting the activation of NF-

B and NLRP3 inflammasomes to alleviate HN

关键词

田黄方高尿酸血症肾病网络药理学肾脏损伤炎症纤维化

Keywords

Tianhuang formulahyperuricemia nephropathynetwork pharmacologyrenal injuryinflammationfibrosis

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