天津医药

天津医药 ›› 2025, Vol. 53 ›› Issue (10): 1027-1032.doi: 10.11958/20252146

• 实验研究 • 上一篇    下一篇

培哚普利对TAA诱导大鼠肝纤维化NOX4/NLRP3信号通路的影响

呼达古拉1(), 马振华2,△(), 卢艳3, 段春兰2, 李凯1   

  1. 1 内蒙古科技大学包头医学院研究生院（邮编014000）
    2 内蒙古科技大学包头医学院第一附属医院消化内科
    3 内蒙古科技大学包头医学院第一附属医院血液室
  • 收稿日期:2025-05-27 修回日期:2025-07-16 出版日期:2025-10-15 发布日期:2025-10-12
  • 通讯作者: △E-mail：mazhenhua912@sina.com
  • 作者简介:呼达古拉（1997），女，硕士在读，主要从事胃肠疾病及肝病方面研究。E-mail：15391024242@163.com

The effect of perindopril on the NOX4/NLRP3 signaling pathway in TAA-induced liver fibrosis in rats

Hudagula 1(), MA Zhenhua2,△(), LU Yan3, DUAN Chunlan2, LI Kai1   

  1. 1 Graduate School, Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014000, China
    2 Department of Gastroenterology, the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology
    3 Blood Room, the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology
  • Received:2025-05-27 Revised:2025-07-16 Published:2025-10-15 Online:2025-10-12
  • Contact: △E-mail：mazhenhua912@sina.com

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摘要：

目的 探讨培哚普利对硫代乙酰胺（TAA）诱导的大鼠肝纤维化烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶4（NOX4）/NOD样受体蛋白3（NLRP3）信号通路的影响。方法 32只SD大鼠随机分为空白组、模型组（TAA 200 mg/kg，2次/周×6周）、TAA+培哚普利低/高剂量组（2/8 mg/kg），每组8只。造模2周后，给药组予相应剂量培哚普利灌胃（4周）；6周末，肝脏病理切片观察肝组织病理变化以及纤维化和炎症程度；生化分析仪检测丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）；酶联免疫吸附试验检测NLRP3、白细胞介素（IL）-1β；免疫组化检测NOX4、NLRP3、胱天蛋白酶1（Caspase-1）、IL-1β蛋白和α-平滑肌激动蛋白（α-SMA）。结果 与空白组比较，模型组肝脏胶原纤维明显增生，大量炎性细胞浸润，大鼠血清ALT、AST水平及NLRP3、IL-1β水平明显升高，大鼠肝组织NOX4、NLRP3、Caspase-1、IL-1β、α-SMA阳性蛋白平均光密度值明显增加（P<0.05）；与模型组比较，低剂量、高剂量组中胶原纤维增生及炎性细胞浸润均明显减少，大鼠血清ALT，AST水平，NLRP3、IL-1β水平明显降低；大鼠肝组织NOX4、NLRP3、Caspase-1、IL-1β、α-SMA阳性蛋白平均光密度值均明显下降（P<0.05），且高剂量组大鼠肝纤维化程度减轻优于低剂量组。结论 培哚普利可能通过抑制NOX4表达进而调控NLRP3信号通路，减轻氧化应激损伤及炎症反应，从而延缓肝脏纤维化进程。

关键词: 肝纤维化, 培哚普利, NADPH氧化酶4, NLR家族, 热蛋白结构域包含蛋白3, 氧化性应激, 炎症

Abstract:

Objective To investigate the effect of perindopril on the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4)/NOD-like receptor protein 3 (NLRP3) signaling pathway in rat liver fibrosis induced by thioacetamide (TAA). Methods Thirty-two SD rats were randomly divided into the blank group, the model group (TAA 200 mg/kg, twice a week for 6 weeks) and the low/high dose group (TAA+ perindopril 2/8 mg/kg), with 8 rats in each group. Two weeks after modeling, the administration group was given the corresponding dose of perindopril by gavage (for 4 weeks). At the end of the 6th week, liver pathological sections were used to observe pathological changes of liver tissue and degrees of fibrosis and inflammation. The biochemical analyzer was used to detect alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Enzyme-linked immunosorbent assay (ELISA) was used to detect NLRP3 and IL-1β. Immunohistochemistry was used to detect NOX4, NLRP3, Caspase-1, IL-1β protein and α -smooth muscle agonist protein (α-SMA). Results Compared with the blank group, liver collagen fibers were significantly proliferated in the model group, a large number of inflammatory cells infiltrated, and serum levels of ALT and AST, as well as NLRP3 and IL-1β in rats were significantly increased. The average optical density values of positive proteins such as NOX4, NLRP3, Caspase-1, IL-1β and α-SMA in rat liver tissue increased significantly (P < 0.05). Compared with the model group, the proliferation of collagen fibers and inflammatory infiltration were significantly reduced in both the low-dose and high-dose groups, and serum levels of ALT and AST, NLRP3 and IL-1β in rats were significantly decreased. The average optical density values of positive proteins such as NOX4, NLRP3, Caspase-1, IL-1β and α-SMA in rat liver tissue decreased significantly (P < 0.05). Moreover, the degree of liver fibrosis reduction in rats was better in the high-dose group than that in the low-dose group. Conclusion Perindopril may regulate the NLRP3 signaling pathway by inhibiting the expression of NOX4, thereby reducing oxidative stress damage and inflammatory responses and thus delaying the process of liver fibrosis.

Key words: hepatic fibrosis, perindopril, NADPH oxidase 4, NLR family, pyrin domain-containing 3 protein, oxidative stress, inflammation

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