Effect and Mechanism of Niuhuang Qingxinwan in Protecting Blood-brain Barrier of Intracerebral Hemorrhage Mice with Tanre Fushi Syndrome
10.13422/j.cnki.syfjx.20251204
- VernacularTitle:牛黄清心丸改善痰热腑实型脑出血小鼠血脑屏障损伤的作用机制
- Author:
Xueyu LING
1
;
Miling ZHANG
2
;
Yuanhao XU
2
;
Liangying BAO
2
;
Shuaishuai GONG
2
;
Junping KOU
2
Author Information
1. Harbin Pharmaceutical Group Shiyitang Pharmaceutical Factory，Harbin 150078，China
2. Department of Pharmacology of Chinese Materia Medica，School of Traditional Chinese Pharmacy，China Pharmaceutical University，Jiangsu Key Laboratory of Traditional Chinese Medicine Evaluation and Translational Research，Nanjing 211100，China
- Publication Type:Journal Article
- Keywords:
Niuhuang Qingxinwan;
Tanre Fushi syndrome;
intracerebral hemorrhage;
blood-brain barrier;
signal transducer and activator of transcription 3 （STAT3）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(24):39-49
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect of Niuhuang Qingxinwan （NHQXW） in improving intracerebral hemorrhage （ICH） with Tanre Fushi （phlegm-heat and fu-organ excess） syndrome by maintaining blood-brain barrier （BBB） integrity， and to explore its potential mechanism. MethodsMale mice were administered with 15% autologous feces for 3 consecutive days to simulate spontaneous Tanre Fushi syndrome， followed by surgical induction of collagenase-induced ICH on the fourth day. Mice were randomly assigned to seven groups： Sham， Sham+NHQXW-H， collagenase， collagenase+feces， and NHQXW intervention groups at low （NHQXW-L， 0.225 g·kg-1）， medium （NHQXW-M， 0.45 g·kg-1）， and high （NHQXW-H， 0.9 g·kg-1） doses. Treatments were administered for 3 days after surgery. NHQXW effects on Tanre Fushi syndrome were assessed via fecal water content and small intestinal carbon propulsion rate. Protective effects of NHQXW against ICH with Tanre Fushi syndrome were evaluated by measuring hematoma volume， neurological deficits， and brain water content. BBB integrity was further assessed using Evans blue staining， hematoxylin-eosin （HE） staining， immunofluorescence， and Western blot for Claudin-5， plasmalemma vesicle-associated protein （PLVAP）， matrix metalloproteinase （MMP）-2， and MMP-9. The potential mechanism of NHQXW was investigated by detecting protein expression of protein kinase B （Akt）， extracellular signal-regulated kinase 1/2 （ERK1/2）， signal transducer and activator of transcription 3 （STAT3）， Yes-associated protein （YAP）， and their phosphorylated forms. ResultsCompared with the collagenase+feces group， NHQXW-M and NHQXW-H significantly reduced fecal water content （P<0.05， P<0.01） and intestinal propulsion rate （P<0.01）， alleviated neurological deficits （P<0.01）， decreased hematoma volume （P<0.01） and Evans blue extravasation （P<0.01）， increased Claudin-5 protein expression （P<0.05， P<0.01） and fluorescence intensity （P<0.01）， and decreased PLVAP protein expression （P<0.01） and fluorescence intensity （P<0.05， P<0.01）， as well as MMP-2 （P<0.05， P<0.01） and MMP-9 （P<0.01） expression. NHQXW-H downregulated p-Akt （P<0.05）， p-ERK1/2 （P<0.05）， p-STAT3 （P<0.01）， and p-YAP （P<0.05）， with the most significant effect observed on STAT3 phosphorylation. ConclusionNHQXW effectively alleviates neurological deficits and BBB injury in ICH mice with Tanre Fushi syndrome， primarily by inhibiting STAT3 activation.
