Based on TXNIP/NLRP3/Caspase-1 pathway to explore the mechanism of <italic style="font-style: italic">Qingre Zhixue</italic> Formula combined with tripterygium wilfordii multiglucoside in the treatment of Henoch-Schönlein purpura nephritis in rats

WANG Long; DING Ying; XU Shanshan; DAI Yanlin; ZHANG Xia

doi:10.3969/j.issn.1006-2157.2023.04.005

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Based on TXNIP/NLRP3/Caspase-1 pathway to explore the mechanism of Qingre Zhixue Formula combined with tripterygium wilfordii multiglucoside in the treatment of Henoch-Schönlein purpura nephritis in rats

Special Theme: “You Gu Wu Yun” | 更新时间：2023-05-09

- Based on TXNIP/NLRP3/Caspase-1 pathway to explore the mechanism of Qingre Zhixue Formula combined with tripterygium wilfordii multiglucoside in the treatment of Henoch-Schönlein purpura nephritis in rats
- Journal of Beijing University of Traditional Chinese Medicine Vol. 46, Issue 4, Pages: 476-483(2023)
- 作者机构：
  
  1.河南中医药大学儿科医学院　郑州　450046
  2.河南中医药大学第一附属医院
- 作者简介：
  
  ZHANG Xia, Ph.D., Chief Physician, Master’s Supervisor. The First Affiliated Hospital of Henan University of Chinese Medicine, No.19, Renmin Road, Jinshui District, Zhengzhou 450003.E-mail: zhangxia0600@163.com
- 基金信息：
  
  National Natural Science Foundation of China(81873343);Special Project of Scientific Research on Traditional Chinese Medicine in Henan Province(2023ZY2044)
- DOI：10.3969/j.issn.1006-2157.2023.04.005
  CLC： R285.5
- Received：27 November 2022，
  
  Online First：24 February 2023，
  
  Published：30 April 2023
- 稿件说明：
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WANG Long, DING Ying, XU Shanshan, et al. Based on TXNIP/NLRP3/Caspase-1 pathway to explore the mechanism of Qingre Zhixue Formula combined with tripterygium wilfordii multiglucoside in the treatment of Henoch-Schönlein purpura nephritis in rats[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(4): 476-483. DOI: 10.3969/j.issn.1006-2157.2023.04.005.
DOI：

WANG Long, DING Ying, XU Shanshan, et al. Based on TXNIP/NLRP3/Caspase-1 pathway to explore the mechanism of Qingre Zhixue Formula combined with tripterygium wilfordii multiglucoside in the treatment of Henoch-Schönlein purpura nephritis in rats[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023, 46(4): 476-483. DOI: 10.3969/j.issn.1006-2157.2023.04.005. DOI：

摘要

目的

探讨清热止血方联合雷公藤多苷对过敏性紫癜性肾炎模型大鼠的作用机制。

方法

腹腔注射卵白蛋白与完全弗氏佐剂复制过敏性紫癜性肾炎大鼠模型。将造模成功的54只大鼠按照随机数字表法分为模型组(

＝11)、清热止血方组(3.17 mg/kg，

＝11)、雷公藤多苷组(4.69 mg/kg，

＝11)、联合组(清热止血方3.17 mg/kg＋雷公藤多苷4.69 mg/kg，

＝11)、激素组(醋酸泼尼松2.34 mg/kg，

＝10)，另设空白组(

＝9)。各给药组给予相应药物灌胃，空白组及模型组予等量的生理盐水灌胃，2次/d，连续灌胃4周。采用尿液分析仪检测大鼠尿红细胞计数及24 h尿蛋白定量；采用透射电镜观察大鼠肾小球系膜区病变情况；采用蛋白质印迹法及实时荧光PCR法检测大鼠肾脏组织硫氧还蛋白相互作用蛋白(TXNIP)、NOD样受体蛋白3(NLRP3)、半胱氨酸天冬氨酸蛋白酶－1(Caspase-1)、白细胞介素－1β(IL-1β)的蛋白及mRNA表达量。

结果

与模型组比较，各给药组大鼠尿红细胞计数，24 h尿蛋白定量，肾脏组织中TXNIP、NLRP3、Caspase-1蛋白表达量均降低(

0.05)；各给药组大鼠肾小球系膜增生及基底膜增厚均改善，其中，联合组改善最明显；联合组、雷公藤多苷组及激素组大鼠肾脏组织中TXNIP、NLRP3 mRNA表达量降低(

0.05)，联合组、激素组大鼠肾脏组织中IL-1β mRNA表达量降低(

0.05)。与联合组比较，其余给药组大鼠尿红细胞计数，24 h尿蛋白定量，肾脏组织中TXNIP、NLRP3蛋白及IL-1β mRNA表达量均升高(

0.05)；雷公藤多苷组大鼠肾脏组织中TXNIP、NLRP3 mRNA表达量升高(

0.05)，清热止血方组大鼠肾脏组织中NLRP3 mRNA表达量升高(

0.05)，激素组大鼠肾脏组织中TXNIP、NLRP3、IL-1β mRNA表达量均升高(

0.05)。

结论

清热止血方联合雷公藤多苷可有效降低过敏性紫癜性肾炎模型大鼠尿红细胞计数及24 h尿蛋白定量，减轻肾脏损伤，可能与抑制TXNIP/NLRP3/Caspase-1炎性通路的激活相关。

Abstract

Objective

We aimed to explore the therapeutic mechanism of

Qingre Zhixue

Formula combined with tripterygium wilfordii multiglucoside in rats with Henoch-Schönlein purpura nephritis (HSPN).

Methods

An HSPN rat model was established by intraperitoneal injection of ovalbumin and complete Freund’s adjuvant. According to the random number table method

54 rats with successful model were divided into the model group (

=11)

the

Qingre Zhixue

Formula group (3.17 mg/kg

=11)

the tripterygium wilfordii multiglucoside group (4.69 mg/kg

=11)

the combined group (3.17 mg/kg

Qingre Zhixue

Formula + 4.69 mg/kg tripterygium wilfordii multiglucoside

=11)

the hormone group (prednisone acetate 2.34 mg/kg

=10)

in addition

nine rats in the blank group. Rats in the blank group and the model group were gavaged with the same amount of saline

and rats in the other groups were gavaged with corresponding drugs twice a day for 4 weeks. The urinary red blood cell count and the 24-hour urine protein quantification were determined by urine analyzer. The pathological changes of the mesangial area of rats were observed by transmission electron microscopy. The protein and mRNA expression levels of thioredoxin interacting protein (TXNIP)

Nod-like receptor protein 3 (NLRP3)

cysteine aspartic protease-1 (Caspase-1) and interleukin-1β (IL-1β) in rat kidney tissue were detected by Western blotting and real-time PCR.

Results

Compared with the model group

the urinary red blood cell count

the 24-hour urine protein quantification

the protein expression levels of TXNIP

NLRP3 and Caspase-1 in the kidney tissues of rats in all treatment groups were reduced (

0.05). The glomerular thylakoid hyperplasia and basement membrane thickening of rats in each treatment group were improved

among which the most obvious improvement was observed in the combined group. The mRNA expression levels of TXNIP and NLRP3 in the kidney tissues of the rats in the combined group

the tripterygium wilfordii multiglucoside group and the hormone group were decreased (

0.05)

the mRNA expression levels of IL-1β in the kidney tissues of the rats in the combined group and the hormone group were decreased (

0.05). Compared with the combined group

the urinary red blood cell count

the 24-hour urine protein quantification

the protein expression of TXNIP and NLRP3

and the mRNA expression levels of IL-1β in the kidney tissues of the rats in the remaining treatment groups were all increased (

0.05). The mRNA expression levels of TXNIP and NLRP3 in the kidney tissues of the rats in the tripterygium wilfordii multiglucoside group were increased (

0.05)

the mRNA expression levels of NLRP3 in the kidney tissues of the rats in the

Qingre Zhixue

Formula group were increased (

0.05)

the mRNA expression levels of TXNIP

NLRP3 and IL-1β were increased in the kidney tissues of the rats in the hormone group (

0.05).

Conclusion

Qingre Zhixue

Formula combined with tripterygium wilfordii multiglucoside can effectively reduce the urinary red blood cell count and the 24-hour urine protein quantification in HSPN rats

and alleviate kidney injury

which may be related to the inhibition of the TXNIP/NLRP3/Caspase-1 inflammatory pathway.

关键词

Keywords

references

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Based on TXNIP/NLRP3/Caspase-1 pathway to explore the mechanism of Qingre Zhixue Formula combined with tripterygium wilfordii multiglucoside in the treatment of Henoch-Schönlein purpura nephritis in rats

DOI：10.3969/j.issn.1006-2157.2023.04.005

摘要

Abstract

关键词

Keywords

references