化湿润燥方调控Hippo-YAP/TAZ表达对干燥综合征小鼠颌下腺细胞凋亡和功能的影响

黄子玮; 陶庆文; 廖佳禾; 余新波; 贺倩; 唐博杰; 罗静

doi:10.3969/j.issn.1006-2157.2024.11.008

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化湿润燥方调控Hippo-YAP/TAZ表达对干燥综合征小鼠颌下腺细胞凋亡和功能的影响

实验研究 | 更新时间：2024-12-02

- 化湿润燥方调控Hippo-YAP/TAZ表达对干燥综合征小鼠颌下腺细胞凋亡和功能的影响
- Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sjögren′s syndrome model mice by regulating Hippo-YAP/TAZ expression
- 北京中医药大学学报 2024年47卷第11期页码：1527-1540
- 作者机构：
  
  1.北京中医药大学研究生院　北京　100029
  2.中日友好医院中医风湿病科免疫炎性疾病北京市重点实验室
- 作者简介：
  
  黄子玮，女，在读博士生
  #罗静，女，博士，副主任医师，主要研究方向：中医药治疗风湿病，E-mail：luojinggg@sina.com
- 基金信息：
  
  国家自然科学基金项目(81804042);首都卫生发展科研专项(2024-1-4065);中央高水平医院临床科研业务费专项成果转化项目(2023-NHLHCRF-YXHZ-ZRMS-07);北京中医药科技发展基金项目(BJZYQN-2023-04);中日友好医院“菁英计划”人才培育工程(ZRJY2024-GG08);中华中医药学会风湿病分会青年培英计划项目(202327-007)
- DOI：10.3969/j.issn.1006-2157.2024.11.008
  中图分类号： R285.5
- 收稿日期：2024-05-16，
  
  网络出版日期：2024-10-11，
  
  纸质出版日期：2024-11-30
- 稿件说明：
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黄子玮, 陶庆文, 廖佳禾, 等. 化湿润燥方调控Hippo-YAP/TAZ表达对干燥综合征小鼠颌下腺细胞凋亡和功能的影响[J]. 北京中医药大学学报, 2024,47(11):1527-1540.

HUANG Ziwei, TAO Qingwen, LIAO Jiahe, et al. Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sjögren′s syndrome model mice by regulating Hippo-YAP/TAZ expression[J]. Journal of beijing university of traditional chinese medicine, 2024, 47(11): 1527-1540.
黄子玮, 陶庆文, 廖佳禾, 等. 化湿润燥方调控Hippo-YAP/TAZ表达对干燥综合征小鼠颌下腺细胞凋亡和功能的影响[J]. 北京中医药大学学报, 2024,47(11):1527-1540. DOI： 10.3969/j.issn.1006-2157.2024.11.008.

HUANG Ziwei, TAO Qingwen, LIAO Jiahe, et al. Effects of Huashi Runzao Prescription on apoptosis and function of the submandibular gland in Sjögren′s syndrome model mice by regulating Hippo-YAP/TAZ expression[J]. Journal of beijing university of traditional chinese medicine, 2024, 47(11): 1527-1540. DOI： 10.3969/j.issn.1006-2157.2024.11.008.

摘要

目的

探索化湿润燥方调控Hippo-Yes相关蛋白(YAP)/具有PDZ结合基序的转录共激活因子(TAZ)通路对干燥综合征(SS)模型小鼠(NOD/Ltj)颌下腺细胞凋亡和唾液分泌功能的影响。

方法

选取8周龄雌性BALB/c小鼠为空白组，8周龄NOD/Ltj雌性小鼠简单随机抽样分为模型组、羟氯喹组和化湿润燥低、中、高剂量组，给药8周后测量各组小鼠饮水量、唾液流率，采用苏木素－伊红染色检测各组小鼠颌下腺组织病理损伤，免疫组织化学法及蛋白质印迹法检测颌下腺组织中水通道蛋白5(AQP5)、B细胞淋巴瘤/白血病－2蛋白(Bcl-2)、Bcl-2相关X蛋白(Bax)、苄氯素1蛋白(beclin-1)、YAP、磷酸化YAP(p-YAP)、TAZ蛋白表达，TUNEL染色检测各组颌下腺细胞凋亡率。

结果

与空白组比较，模型组小鼠颌下腺组织中Hippo-YAP/TAZ通路被抑制，淋巴细胞浸润增多、饮水量增加、唾液流率降低、AQP5蛋白表达减少、唾液腺细胞凋亡率增加(均

0.05)。与其他给药组比较，化湿润燥中剂量能够明显激活Hippo-YAP/TAZ通路，改善颌下腺组织淋巴细胞浸润、减少小鼠饮水量、升高唾液流率、增加AQP5蛋白表达、减少唾液腺细胞的凋亡率(均

0.05)。

结论

化湿润燥方能减轻SS模型小鼠颌下腺细胞病理损伤和凋亡，改善颌下腺组织的整体分泌功能，这可能与其激活Hippo通路、下调YAP/TAZ水平相关。

Abstract

Objective

To explore the effects of modulating the Hippo-YAP/TAZ pathway using

Huashi Runzao

Prescription (HRP) on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic (NOD/Ltj) mouse model of Sjögren′s syndrome (SS).

Methods

Eight-week-old female BALB/c mice were selected as the blank group. Eight-week-old female NOD/Ltj were randomly divided into the model

HRP-L

HRP-M

HRP-H

and hydroxychloroquine sulphate (HCQ) groups. After eight weeks of drug administration

the water consumption and salivary flow rate of each group were recorded. The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining

the apoptosis rate of the submandibular gland was determined using TUNEL staining

and AQP5

Bax

Bcl-2

beclin-1

YAP

p-YAP

and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.

Results

Compared with the blank group

the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group

lymphocyte infiltration increased

water consumption increased

salivary flow rate decreased

AQP5 expression decreased

and submandibular gland cells apoptosis rate increased (

0.05). Compared with all other administered groups

in the HRP-M group

the Hippo-YAZ/TAZ pathway was significantly activated

lymphocyte infiltration in submandibular gland tissues was reduced

water consumption was reduced

the salivary flow rate and AQP5 expression were increased

and the apoptosis rate of submandibular gland cells was reduced (

0.05).

Conclusion

HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice. It improved the overall secretory function of submandibular gland tissues

which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.

关键词

Keywords

references

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