Mechanism of Zhihuang Zhitong Granule in Treatment of Rat Gouty Arthritis Based on NALP3 Inflammasome Pathway

ZHOU Zi-peng; ZHENG Fu-zeng; MENG Qing-liang; FAN Wei

doi:10.13422/j.cnki.syfjx.20180728

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Mechanism of Zhihuang Zhitong Granule in Treatment of Rat Gouty Arthritis Based on NALP3 Inflammasome Pathway

更新时间：2024-01-04

- Mechanism of Zhihuang Zhitong Granule in Treatment of Rat Gouty Arthritis Based on NALP3 Inflammasome Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 24, Issue 8, Pages: 140-147(2018)
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20180728
  CLC： R285.5
- Published：2018
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ZHOU Zi-peng, ZHENG Fu-zeng, MENG Qing-liang, et al. Mechanism of Zhihuang Zhitong Granule in Treatment of Rat Gouty Arthritis Based on NALP3 Inflammasome Pathway[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(8): 140-147.
DOI：

ZHOU Zi-peng, ZHENG Fu-zeng, MENG Qing-liang, et al. Mechanism of Zhihuang Zhitong Granule in Treatment of Rat Gouty Arthritis Based on NALP3 Inflammasome Pathway[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(8): 140-147. DOI： 10.13422/j.cnki.syfjx.20180728.

摘要

目的：探究栀黄止痛颗粒治疗大鼠痛风性关节炎以及对NALP3炎性体（NACHT-LRR-PYD-containing proteins-3，NALP3）信号通路的影响。方法：将SD大鼠分为6组，分别为正常组，模型组（踝关节腔注射尿酸钠制备），栀黄止痛颗粒低、中、高剂量（1.0，2.5，5.0 g·kg-1）和阳性药组（秋水仙碱，3.0 g·kg-1），酶联免疫吸附法（ELISA）法测定血清中肿瘤坏死因子-α（TNF-α），白细胞介素-6（IL-6），白细胞介素-1β（IL-1β）含量，造模后24 h评定大鼠步态以及关节炎症指数，造模前、造模后6，12，24，48 h测定大鼠裸关节肿胀度。苏木素-伊红（HE）染色观察各组大鼠踝关节组织病理学变化，逆转录-聚合酶链反应法（RT-PCR），蛋白免疫印迹法（Western blot），免疫组化法检测关节组织中NLRP3，IL-1β，凋亡相关斑点样蛋白（ASC），半胱天冬酶-1（Caspase-1）表达。结果：与正常组比较，模型组血清中TNF-α，IL-6，IL-1β含量显著升高（P < 0.01）；与模型组比较，秋水仙碱组、栀黄止痛颗粒低、中、高剂量组显著降低TNF-α，IL-6，IL-1β含量（P < 0.01）。与正常组比较，模型组大鼠步态较差、关节肿胀显著（P < 0.01）；与模型组比较，秋水仙碱组、药物处理组步态、关节肿胀得到所改善，随着药物剂量浓度的增加，步态、关节肿胀分级逐渐降低（P < 0.05，P < 0.01）。与正常组比较，模型组踝关节组织中NLRP3，IL-1β，ASC，Caspase-1 mRNA及蛋白表达显著升高（P < 0.01）；与模型组比较，秋水仙碱组、栀黄止痛颗粒低、中、高剂量组均显著降低NLRP3，IL-1β，ASC，Caspase-1 mRNA及蛋白的表达（P < 0.01）。免疫组化显示，与正常组比较，模型组NLRP3，IL-1β，ASC，Caspase-1表达阳性表达量显著升高，而与模型组比较，秋水仙碱组、栀黄止痛颗粒中、高剂量组显著降低阳性表达率（P < 0.01），具有剂量依赖性。结论：栀黄止痛颗粒能够缓解痛风性关节炎大鼠关节肿胀，其机制可能与抑制NALP3炎性体信号通路有关。

Abstract

Objective: To investigate the application of Zhihuang Zhitong granule in the treatment of gouty arthritis in rats and its effects on NACHT-LRR-PYD-containing proteins-3 inflammasome (NALP3) signaling pathway. Method: The SD rats were divided into six groups

normal group

model group (preparation by sodium urate injection into ankle joint cavity)

Zhihuang Zhitong granule low dose group (1.0 g · kg-1)

middle dose group (2.5 g · kg-1)

high dose group (5 g · kg-1) and positive group (colchicine

3.0 g · kg-1). The levels of serum tumor necrosis factor-α (TNF-α)

interleukin-6 (IL-6) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA); the gait and joint inflammation index at 24 h after modeling were evaluated; and the swelling degree of the naked joint was assessed before modeling

48 h after modeling. Hematoxylin eosin staining (HE) was used to observe the histopathological changes of ankle joint in each group; reverse transcription polymerase chain reaction (RT-PCR)

Western blot and immunohistochemistry were used to detect the expression of NLRP3

IL-1β

apoptosis-associated speck-like protein (ASC) and Caspase-1 in the joint tissue. Result: Serum levels of TNF-α

IL-6 and IL-1β in model group were significantly increased in the model group as compared with the normal group (P<0.01). As compared with the model group

the levels of TNF-α

IL-6 and IL-1β were decreased in positive group

medium and high dose Zhihuang Zhitong granule groups (P<0.01). As compared with the normal group

the rats in the model group had poor gait and swelling joint (P<0.01); as compared with the model group

the poor gait and joint swelling got improved in the positive group and drug treatment groups

and the gait and joint swelling grades decreased gradually with the increase of drug concentration (P<0.05

P<0.01). As compared with the normal group

the NLRP3

IL-1β

ASC

and Caspase-1 mRNA

protein expression levels in the ankle joint tissue were increased in model group (P<0.01)

and these levels were significantly decreased in positive group

middle dose and high dose Zhihuang Zhitong granule groups as compared with the model group (P<0.01). Immunohistochemistry showed that

as compared with the normal group

the positive expression rate of NLRP3

IL-1β

ASC and Caspase-1 was increased in model group; and as compared with the model group

the positive expression rate was decreased in positive group

low dose

middle dose and high dose Zhihuang Zhitong granule groups (P<0.01) in a dose-dependent manner. Conclusion: Zhihuang Zhitong granule can alleviate the swelling of joint in rats with gouty arthritis

and its mechanism may be related to the inhibition of NALP3 inflammatory signaling pathway.

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Related Institution

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