Influences of theaflavins on neuronal apoptosis and blood-brain barrier in rats with cerebral hemorrhage by regulating CaMKK2/AMPK signaling pathway
10.12092/j.issn.1009-2501.2022.11.005
- Author:
Rongrong PAN
1
;
Yinghao ZHI
1
;
Yongxi JIN
1
;
Xiahui ZHOU
2
Author Information
1. Departmentof Rehabilitation, Wenzhou Hospital of Traditional Chinese Medicine
2. Office of Drug Clinical Trial Institution of Wenzhou Hospital of Traditional Chinese Medicine
- Publication Type:Journal Article
- Keywords:
blood-brain barrier;
calcium/calmodulin-dependent protein kinase kinase 2/5'-adenosine monophosphate-activated protein kinase signaling pathway;
cerebral hemorrhage;
neuronal apoptosis;
theaflavins
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2022;27(11):1240-1246
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate t h e impacts of theaflavins (TFs) on neuronal apoptosis and blood-brain barrier (BBB) by regulating the calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2)/5 '-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. METHODS: Ninety rats were randomly separated into sham operation group, model group, low-dose TFs group (20 mg/kg TFs), high-dose TFs group (40 mg/kg TFs), and high-dose TFs + STO-609 group (40 mg/kg TFs + 10 ΜL CaMKK2 inhibitor-STO-609), positive control group (2 mg/kg nimodipine injection), with 15 rats in each group. A rat model of intracerebral hemorrhage was induced by collagenase type VII. The behavior of rats and the water content of brain tissue were detected; the serum of rats was isolated, and the levels of inflammatory factors-vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) were detected; brain tissue around the hematoma was collected to detect neuronal apoptosis, BBB permeability parameter-EB level, and expressions of p-CaMKK2/CaMKK2, p-AMPK/AMPK and apoptosis-related protein Bax. RESULTS: Compared with the sham operation group, the mNSS score, ICAM-1, TNF-α, VCAM-1, brain tissue water content, apoptosis rate, EB level and Bax protein expression in the model group were all increased, both pCaMKK2/CaMKK2 and p-AMPK/AMPK were decreased (P < 0.05); compared with the model group, the mNSS score, ICAM-1, TNF-α, VCAM-1, brain water content, apoptosis rate, EB level and Bax expression in the low- and high-dose TFs groups and the positive control group were all lower than those in the model group, both pCaMKK2/CaMKK2 and p-AMPK/AMPK were increased (P < 0.05); compared with the high-dose TFs group, the mNSS score, ICAM-1, TNF-α, VCAM-1, brain tissue water content, apoptosis rate, EB level and Bax expression were all increased in the high dose TFs + STO-609 group, both p-CaMKK2/CaMKK2 and p-AMPK/AMPK were decreased (P < 0.05). CONCLUSION: TFs can reduce neuronal apoptosis, inflammatory response, BBB permeability, and play a protective role in rats with cerebral hemorrhage injury. Its mechanism is related to the activation of CaMKK2/AMPK signaling pathway.
