Effect of Xuanfu Daizhe Tang on NLRP3/Caspase-1 Pathway of RE Model Rats

Yuan LIU; Ju LIU; Ya-ting LIU; Jia-meng MIAO; Hong-xia YUAN; Pan-pan YU

doi:10.13422/j.cnki.syfjx.20191906

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Effect of Xuanfu Daizhe Tang on NLRP3/Caspase-1 Pathway of RE Model Rats

Classic Prescriptions | 更新时间：2021-02-09

- Effect of Xuanfu Daizhe Tang on NLRP3/Caspase-1 Pathway of RE Model Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 20, Pages: 13-18(2019)
- 作者机构：
  
  1.天津中医药大学，天津　 300193；
  2.昆山市中医医院，江苏　昆山　 215300；
  3.天津市中西医结合医院　南开医院，天津　 300100
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191906
  CLC： R2-0; R22; R285.5; R289
- Received：19 April 2019，
  
  Published Online：19 June 2019，
  
  Published：20 October 2019
- 稿件说明：
移动端阅览
Yuan LIU, Ju LIU, Ya-ting LIU, et al. Effect of Xuanfu Daizhe Tang on NLRP3/Caspase-1 Pathway of RE Model Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(20): 13-18.
DOI：

Yuan LIU, Ju LIU, Ya-ting LIU, et al. Effect of Xuanfu Daizhe Tang on NLRP3/Caspase-1 Pathway of RE Model Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(20): 13-18. DOI： 10.13422/j.cnki.syfjx.20191906.

摘要

目的：

通过观察旋覆代赭汤对反流性食管炎(RE)模型大鼠炎症小体组成成分及相关炎症因子表达的影响，探究NOD样受体热蛋白结构域相关蛋白3(NLRP3)/半胱氨酸蛋白酶(Caspase)-1信号通路与食管炎症的相关性，阐明旋覆代赭汤治疗RE的作用机制。

方法：

将60只健康雄性Wistar大鼠，随机分为4组，分别为正常组，模型组，旋覆代赭汤组(9.89 g·kg

－1

)，阳性药组(奥美拉唑镁肠溶片＋枸橼酸莫沙必利片，2.58 mg·kg

－1

)，每组15只。除正常组外，其余各组大鼠行“4.2 mm 幽门夹＋2/3胃底结扎术”方法造模。从术后第8天开始，给予相应的药物进行灌胃干预，每日2次，共14 d，第15天处死取动脉血及食管组织。肉眼及光镜下观察食管组织病理学形态，应用酶联免疫吸附测定(ELISA)检测血清中Caspase-1，白细胞介素-1

(IL-1

)的分泌情况，采用蛋白免疫印迹法(Western blot)检测食管组织中NLRP3，Caspase-1，IL-1

的蛋白表达情况。

结果：

食管黏膜肉眼及镜下观察，与正常组比较，模型组损伤最为严重，积分最高。与正常组比较，模型组大鼠血清中Caspase-1，IL-1

的含量和食管组织中NLRP3，Caspase-1，IL-1

的蛋白表达明显升高(

0.05，

0.01)；与模型组比较，旋覆代赭汤可明显降低大鼠血清中Caspase-1，IL-1

的含量，下调食管组织中NLRP3，Caspase-1，IL-1

的蛋白表达水平(

0.05，

0.01)。

结论：

旋覆代赭汤可以下调炎症小体蛋白组分NLRP3，Caspase-1的表达，降低炎症因子IL-1

的含量，表明此方可能通过抑制NLRP3/Caspase-1信号通路的激活，拮抗食管炎症反应，减少食管炎症损伤，治疗RE。

Abstract

Objective:

To investigate the relationship between NOD-like receptor pyrin domain containing 3(NLRP3)/cysteine aspartate-specific protease(Caspase)-1 signaling pathway and esophageal inflammation by observing the effect of Xuanfu Daizhe Tang on the composition of inflammatory body and the expression of relevant inflammatory factors in rats with reflux esophagitis (RE)

so as to explain the mechanism of Xuanfu Daizhe Tang in treating RE.

Method:

Sixty healthy male Wistar rats were randomly divided into four groups: the normal control group

the model control group

the Xuanfu Daizhe Tang group (9.89 g·kg

-1

) and the positive control group (omeprazole enteric-coated tablets+ mosapride

2.58 mg·kg

-1

)

with 15 rats in each group. Except for the blank control group

the remaining rats were operated by " 4.2 mm pyloric clip+ 2/3 gastric fundus ligation" to establish models. Since the 8

day after the operation

the rats were given corresponding drugs twice a day for 14 days. The arterial blood and esophageal tissues were taken out at the 15

day after the intervention. The pathological morphology of esophagus was observed by naked eyes and under light microscopy. The secretion of cytokines Caspase-1 and interleukin(IL)-1

in serum was detected by enzyme linked immunosorbent assay(ELISA). The expressions of NLRP3

Caspase-1 and IL-1

in esophagus were detected by Western blot.

Result:

Compared with the normal group

the injury of esophageal mucosa in the model group was the most serious. Compared with the normal group

the levels of Caspase-1 and IL-1

in serum and the expression of NLRP3 protein in esophageal tissue of the model group were significantly increased (

0.05

0.01). Compared with the model group

Xuanfu Daizhe Tang could significantly reduce the contents of Caspase-1 and IL-1

in serum of rats

and down-regulate the expressions of NLRP3

Caspase-1 and IL-1

protein in esophageal tissue (

0.05

0.01).

Conclusion:

Xuanfu Daizhe Tang can regulate the expressions of NLRP3 and Caspase-1

and reduce the content of IL-1

suggesting that it may antagonize esophageal inflammatory response

reduce esophageal inflammatory injury and treat RE by inhibiting the activation of NLRP3/Caspase-1 signaling pathway.

关键词

Keywords

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