Fu Guanglei, Wang Hua, Cai Youli, Zhao Hui, Fu Wenjun
Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, People's Republic of China.
School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.
Drug Des Devel Ther. 2018 Jun 12;12:1609-1619. doi: 10.2147/DDDT.S164324. eCollection 2018.
Intracerebral hemorrhage (ICH) is one of the most common acute cerebrovascular diseases with high mortality. Numerous studies have shown that inflammatory response played an important role in ICH-induced brain injury. Theaflavin (TF) extracted from black tea has various biological functions including anti-inflammatory activity. In this study, we investigated whether TF could inhibit ICH-induced inflammatory response in rats and explored its mechanism.
ICH rat models were induced with type VII collagenase and pretreated with TF by gavage in different doses (25 mg/kg-100 mg/kg). Twenty-four hours after ICH attack, we evaluated the rats' behavioral performance, the blood-brain barrier (BBB) integrity, and the formation of cerebral edema. The levels of reactive oxygen species (ROS) and inflammatory cytokines were examined by 2',7'-dichlorofluorescin diacetate and enzyme-linked immunosorbent assay. Nissl staining and transferase dUTP nick end labeling (TUNEL) were aimed to detect the neuron loss and apoptosis, the mechanism of which was explored by Western blot.
It was found that in the pretreated ICH rats TF significantly alleviated the behavioral defects, protected BBB integrity, and decreased the formation of cerebral edema and the levels of ROS as well as inflammatory cytokines (including interleukin-1 beta [IL-1β], IL-18, tumor nectosis factor-alpha, interferon-γ, transforming growth factor beta, and (C-X-C motif) ligand 1 [CXCL1]). Nissl staining and TUNEL displayed TF could protect against the neuron loss and apoptosis via inhibiting the activation of nuclear transcription factor kappa-β-p65 (NF-κβ-p65), caspase-1, and IL-1β. We also found that phorbol 12-myristate 13-acetate, a nonspecific activator of NF-κβ-p65, weakened the positive effect of TF on ICH-induced neural defects and neuron apoptosis by upregulating NF-κβ-related signaling pathway.
TF could alleviate ICH-induced inflammatory responses and brain injury in rats via inhibiting NF-κβ-related pathway, which may provide a new way for the therapy of ICH.
脑出血（ICH）是最常见的急性脑血管疾病之一，死亡率很高。大量研究表明，炎症反应在脑出血所致脑损伤中起重要作用。从红茶中提取的茶黄素（TF）具有多种生物学功能，包括抗炎活性。在本研究中，我们调查了TF是否能抑制大鼠脑出血诱导的炎症反应并探讨其机制。
用VII型胶原酶诱导建立ICH大鼠模型，并通过灌胃给予不同剂量（25mg/kg - 100mg/kg）的TF进行预处理。脑出血发作24小时后，我们评估大鼠的行为表现、血脑屏障（BBB）完整性以及脑水肿的形成。采用二氯二氢荧光素二乙酸酯和酶联免疫吸附测定法检测活性氧（ROS）和炎性细胞因子水平。尼氏染色和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）旨在检测神经元丢失和凋亡，并通过蛋白质免疫印迹法探讨其机制。
发现在预处理的ICH大鼠中，TF显著减轻行为缺陷，保护BBB完整性，减少脑水肿形成以及ROS和炎性细胞因子（包括白细胞介素-1β[IL-1β]、IL-18、肿瘤坏死因子-α、干扰素-γ、转化生长因子-β和（C-X-C基序）配体1[CXCL1]）水平。尼氏染色和TUNEL显示TF可通过抑制核转录因子κ-β-p65（NF-κβ-p65）、半胱天冬酶-1和IL-1β的激活来防止神经元丢失和凋亡。我们还发现，佛波酯，一种NF-κβ-p65的非特异性激活剂，通过上调NF-κβ相关信号通路削弱了TF对脑出血诱导的神经缺陷和神经元凋亡的积极作用。
TF可通过抑制NF-κβ相关通路减轻大鼠脑出血诱导的炎症反应和脑损伤，这可能为脑出血的治疗提供新途径。
