人参皂苷Rg1通过TNF-α/TNFR1/RIPKs通路调控急性肾损伤致急性肺损伤的保护机制研究

doi:10.13418/j.issn.1001-165x.2023.4.07

中国临床解剖学杂志 ›› 2023, Vol. 41 ›› Issue (4): 409-415.doi: 10.13418/j.issn.1001-165x.2023.4.07

人参皂苷Rg1通过TNF-α/TNFR1/RIPKs通路调控急性肾损伤致急性肺损伤的保护机制研究

曹瀛心^1,3，迟晓晨²，包翠芬²，李婷钰¹，刘霞¹*

锦州医科大学 1.组织胚胎学教研室； 2.基础医学实验教学中心； 3.附属第一医院重症医学科一病区，辽宁锦州 121001

收稿日期:2022-03-01 出版日期:2023-07-25 发布日期:2023-08-02
通讯作者: 刘霞，教授，E-mail：Luisliu0908@163.com
作者简介:曹瀛心（1989-），女，辽宁锦州人，硕士，研究方向为缺血再灌注损伤机制及防治，Email：yingxin_8904@163.com
基金资助:
国家自然科学基金资助项目（No. 81774116）；辽宁省教育厅项目（No.JYTJCZR2020083）

Study on the protective mechanism of Ginsenoside Rg1 through TNF-α/TNFR1/RIPKs pathway to regulate acute lung injury induced by acute kidney injury

Cao Yingxin ^1、3, Chi Xiaochen ², Bao Cuifen ², Li Tingyu¹, Liu Xia ¹*

1. Department of Histology and Embryology, Jinzhou Medical University, Jinzhou 121001, Liaoning Province, China; 2. Experimental Teaching Center of Basic Medicine, Jinzhou Medical University, Jinzhou 121001, Liaoning Province, China; 3.The First Ward of Department of Intensive Care Unit ,The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, Liaoning Province, China

Received:2022-03-01 Online:2023-07-25 Published:2023-08-02

摘要/Abstract

摘要： 目的探讨人参皂苷Rg1对急性肾损伤致急性肺损伤的保护作用及其调控机制。方法将60只雄性昆明小鼠随机分成4组，每组15只：A组（假手术组），B组（模型组），C组（人参皂苷Rg1组），D组（Nec-1对照组）。制备急性肾损伤模型，24 h后检测血清肌酐（serum creatinine，Scr）、尿素氮（blood urea nitrogen，BUN）含量，测量肺组织湿/干重比，应用HE染色观察肺组织病理改变，ELISA法检测血清肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6），白细胞介素-8（IL-8）等细胞因子表达，免疫组化和免疫印迹法检测肿瘤坏死因子受体1（tumor necrosis factor receptor 1，TNFR1）、肿瘤坏死因子受体蛋白激酶（receptor interacting protein kinase，RIPK）表达。结果与A组相比，B组Scr、BUN含量明显升高，C组、D组含量较B组均明显降低（P<0.01）；与A组相比，B组肺组织湿/干重比明显升高，C、D组较B组均明显降低（P<0.01）；A组为正常肺泡结构，B组部分肺泡腔塌陷，部分细胞变性坏死，可见明显的炎细胞浸润。与B组相比，C组、D组肺部损伤程度减轻；与A组比较，B组血清中细胞因子TNF-α、IL-1β、IL-6，IL-8水平显著增高，C、D组较B组均明显降低（P<0.01）；B组TNFR1、RIPK1、RIPK3蛋白含量明显高于A组，C、D组较B组均明显降低（P<0.01）。结论人参皂苷Rg1可改善急性肾损伤所诱导的急性肺损伤，其机制可能与抑制TNF-α/TNFR1/RIPKs信号通路有关。

关键词: 人参皂苷Rg1； , , TNF-α/TNFR1/RIPKs； , , 急性肾损伤； , , 急性肺损伤

Abstract: Objective To investigate the protective and regulative mechanism of Ginsenoside Rg1 on acute kidney injury (AKI) induced acute lung injury. Methods Sixty male Kunming mice were randomly divided into 4 groups with 15 mice per group: Group A (sham operation group), Group B (model group), Group C (Ginsenoside Rg1 group), and Group D (necrostatin-1 control group). AKI models were prepared，after 24h, the serum level of serum creatinine (Scr) and blood urea nitrogen (BUN) were detected. The wet/dry weight ratio of lung tissues were also measured. Pathological changes of lung tissues were evaluated by HE staining. Expression of tumor necrosis factor-α (TNF-α), IL-1β, IL-6 and IL-8 were detected by ELISA. Expressions of tumor necrosis factor receptor 1 (TNFR1) and receptor interacting protein kinase (RIPK) were observed by immunohistochemistry and western blotting. Results (1) Compared with Group A, the serum level of Scr and BUN in Group B were significantly increased, while compared with Group B, the serum level of Scr and BUN in Group C and Group D were significantly decreased (P<0.01). (2) Compared with Group A, the wet/dry ratio of lung tissues in Group B was significantly increased. Compared with Group B, the wet/dry ratio of lung tissues in Group C and Group D was significantly decreased (P<0.01). HE staining showed that the lung tissues structure of Group A was basically intact, while part of alveolar cavity was collapsed, cells were necrotic with the serious infiltration of inflammatory cells in Group B. Compared with Group B, the lung injury degree of Group C and Group D was alleviated. (3) ELISA showed that TNF-α, IL-1β, IL-6 and IL-8 in serum of Group B were significantly increased compared with Group A, while in Group C and Group D were significantly decreased compared with Group B (P<0.01). (4) Immunohistochemical and western blotting results showed that the protein content of TNFR1, RIPK1 and RIPK3 in Group B were significantly increased compared with Group A, while in Group C and Group D were significantly decreased compared with Group B (P<0.01). Conclusions Ginsenoside Rg1 can alleviate the acute lung injury induced by acute kidney injury, the mechanism may be related to the inhibition of TNF-α/TNFR1/RIPKs pathway.

Key words: Ginsenoside Rg1; , , TNF-α/TNFR1/RIPKs; , , AKI; , , ALI ,

中图分类号:

R329

曹瀛心, 迟晓晨, 包翠芬, 李婷钰, 刘霞. 人参皂苷Rg1通过TNF-α/TNFR1/RIPKs通路调控急性肾损伤致急性肺损伤的保护机制研究[J]. 中国临床解剖学杂志, 2023, 41(4): 409-415.

Cao Yingxin, Chi Xiaochen, Bao Cuifen, Li Tingyu, Liu Xia . Study on the protective mechanism of Ginsenoside Rg1 through TNF-α/TNFR1/RIPKs pathway to regulate acute lung injury induced by acute kidney injury[J]. Chinese Journal of Clinical Anatomy, 2023, 41(4): 409-415.

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人参皂苷Rg1通过TNF-α/TNFR1/RIPKs通路调控急性肾损伤致急性肺损伤的保护机制研究

Study on the protective mechanism of Ginsenoside Rg1 through TNF-α/TNFR1/RIPKs pathway to regulate acute lung injury induced by acute kidney injury

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