[1]吴辉振,彭 坚,夏艳琼.瑞马唑仑通过调节Notch-1/Hes信号通路对烧伤脓毒症模型大鼠肠道损伤的作用机制研究[J].现代检验医学杂志,2025,40(02):150-155.[doi:10.3969/j.issn.1671-7414.2025.02.028]
　WU Huizhen,PENG Jian,XIA Yanqiong.Effect of Remazolam on Intestinal Injury in Burn Sepsis Model Rats by Regulating the Notch-1/Hes Signaling Pathway[J].Journal of Modern Laboratory Medicine,2025,40(02):150-155.[doi:10.3969/j.issn.1671-7414.2025.02.028]
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瑞马唑仑通过调节Notch-1/Hes信号通路对烧伤脓毒症模型大鼠肠道损伤的作用机制研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年02期
页码:
150-155
栏目:
论著
出版日期:
2025-03-15

文章信息/Info

Title:
Effect of Remazolam on Intestinal Injury in Burn Sepsis Model Rats by Regulating the Notch-1/Hes Signaling Pathway
文章编号:
1671-7414（2025）02-150-06
作者:
吴辉振; 彭 坚; 夏艳琼
（武汉市第三医院麻醉科，武汉 430070）
Author(s):
WU Huizhen; PENG Jian; XIA Yanqiong
(Department of Anesthesiology，Wuhan Third Hospital， Wuhan 430070，China)
关键词:
瑞马唑仑; Notch-1/ 发状分裂相关增强子信号通路; 烧伤脓毒症; 肠道损伤
分类号:
R-332
DOI:
10.3969/j.issn.1671-7414.2025.02.028
文献标志码:
A
摘要:
目的 探究瑞马唑仑（RZ）调节Notch-1/ 发状分裂相关增强子（Hes）信号通路对烧伤脓毒症大鼠肠道损伤的影响。方法 将60 只SD 大鼠随机分为正常组（Normal 组）、模型组（Model 组）、低剂量RZ 组（RZ-L 组，3mg/kg RZ）、高剂量RZ 组（RZ-H 组，6mg/kg RZ）和高剂量RZ+Notch-1 激活剂Jagged1 组（RZ-H+Jagged1 组，6mg/kg RZ+0.67mg/kg Jagged1），每组12 只。在大鼠背部建立20% 总体表面积（TBSA）Ⅲ度烫伤（烧伤）模型，之后注射铜绿假单胞菌制备烧伤脓毒症模型。HE 染色观察回肠组织病理变化，并进行肠黏膜损伤评分（Chiu’s 评分）。ELISA 法检测血清内毒素、D- 乳酸和二胺氧化酶（DAO）及回肠组织白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）、髓过氧化物酶（MPO）的水平。RT-qPCR 法检测回肠组织Notch-1，Hes mRNA 表达。Western Blot 检测回肠组织Notch-1/Hes 信号通路相关蛋白表达。结果 与Normal 组相比，Model 组大鼠肠黏膜损伤评分（5.30±0.48分vs 1.00±0.52 分）、血清内毒素（135.69±16.24 pg/ml vs 62.48±3.23 pg/ml），D- 乳酸（1 403.58±68.97 pg/ml vs752.06±25.29 pg/ml）和DAO 水平（137.55±12.37 pg/ml vs 58.52±4.43 pg/ml）、回肠组织IL-6（186.45±16.37 ng/mlvs 21.32±3.66 ng/ml），TNF-α（163.37±11.40 ng/ml vs 15.52±1.03 ng/ml）和MPO 水平（8.94±0.92 U/ml vs 2.35±0.33U/ml） 及Notch-1 mRNA（1.86±0.19 vs 1.00±0.10） 和蛋白（0.79±0.08 vs 0.21±0.02），Hes-1 mRNA（2.13±0.21vs 1.00±0.12）和蛋白（0.88±0.09 vs 0.32±0.03）表达水平均升高，差异具有统计学意义（t=14.294 ～ 47.368，均P＜ 0.05）。与Model 组相比，RZ-L 组和RZ-H 组相应指标变化与上述相反，差异具有统计学意义（tRZ-L=5.650 ～ 21.448，tRZ-H=4.435 ～ 42.403，均P ＜ 0.05）。Notch-1 激活剂Jagged1 减弱了RZ 对烧伤脓毒症大鼠肠道损伤的治疗作用。结论RZ 可能通过抑制Notch-1/Hes 信号通路减轻烧伤脓毒症模型大鼠的肠道损伤。
Abstract:
Objective To investigate the effect of Remazolam (RZ) on intestinal injury in burn sepsis rats by regulating the Notch-1/hairy and enhancer of split homolog(Hes) signaling pathway. Methods Sixty SPF grade SD male rats were randomly separated into Normal group, Model group, low-dose RZ group (RZ-L group, 3 mg/kg RZ), high-dose RZ group (RZ-H group, 6 mg/kg RZ) and high-dose RZ+Notch-1 activator Jagged1 group (RZ-H+Jagged1 group, 6 mg/kg RZ+0.67 mg/kg Jagged1), with 12 rats in each group. A burn sepsis model was prepared by establishing a 20% total surface area (TBSA) third-degree burn (burn) model on the back of rats, followed by injection of Pseudomonas aeruginosa. HE staining was applied to observe rat ileum tissue’s pathological changes and assess intestinal mucosal damage score (Chiu’s score). ELISA method was used to detect the levels of serum endotoxin, D-lactate, diamine oxidase (DAO), interleukin (IL-6), tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) in rats. RT-qPCR method was applied to detect the expression of Notch-1 and Hes mRNA in rat ileum tissue, and Western Blot was used to detect the expression of Notch-1/Hes signaling pathway-related proteins in rat ileum tissue. Results Compared with the Normal group, the intestinal mucosal injury score (5.30±0.48 vs 1.00±0.52), serum endotoxin (135.69±16.24 pg/ml vs 62.48±3.23 pg/ml), D-lactate (1403.58±68.97 pg/ml vs 752.06±25.29 pg/ml) and DAO levels (137.55±12.37 pg/ml vs 58.52±4.43 pg/ml) , ileal tissue IL-6 (186.45±16.37 ng/ml vs 21.32±3.66 ng/ml), TNF-α (163.37±11.40 ng/ml vs 15.52±1.03 ng/ml) and MPO levels (8.94±0.92 U/ml vs 2.35±0.33 U/ml), Notch-1 mRNA (1.86±0.19 vs 1.00±0.10) and protein ( 0.79±0.08 vs 0.21±0.02),Hes-1 mRNA(2.13±0.21 vs 1.00±0.12) and protein (0.88±0.09, 0.32±0.03) expression levels in the Model group were greatly increased, and the differences were statistically significant (t=14.294 ～ 47.368，all P<0.05). Compared with the Model group, the corresponding indicators of the RZ-L and RZ-H groups showed opposite changes, and the differences were statistically significant (tRZ-L=5.650 ～ 21.448, tRZ-H=4.435 ～ 42.403，all P<0.05). The Notch-1 activator Jagged1 weakened the therapeutic effect of RZ on intestinal injury in burn sepsis rats. Conclusion RZ may alleviate intestinal injury in burn sepsis model rats by inhibiting the Notch-1/Hes signaling pathway.

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备注/Memo

备注/Memo:
基金项目：武汉市科学技术局资助项目（No.2022020801020555）。
作者简介：吴辉振（1989-），男，住院医师，研究方向：麻醉相关疾病，E-mail：zg8db8@163.com。
通讯作者：彭坚（1968-），男，主任医师，研究方向：麻醉相关疾病，E-mail：wuhz1022@163.com。
更新日期/Last Update: 2025-03-15