探讨人脐带间充质干细胞来源外泌体（hUC-MSCs-EXOs）对脑出血（ICH）后炎症反应和神经损伤的影响及其作用机制。

（1）选取健康雄性C57BL/6J小鼠108只，按照随机数字表法分为假手术组（Sham组）、ICH模型组（Model组）和外泌体治疗组（EXO组），每组36只。构建小鼠ICH模型，EXO组在ICH术后4 h经尾静脉注射含100 μg hUC-MSCs-EXOs的磷酸盐缓冲液（PBS）。术后3、7、14 d采用改良神经功能缺损评分（mNSS）评估3组小鼠的神经功能损伤程度。术后7 d，通过HE染色观察病理形态学变化，并检测脑水肿程度及氧化应激指标[丙二醛（MDA）含量、总超氧化物歧化酶（SOD）活性]。（2）建立BV2细胞ICH体外模型，分为对照组（Control组）、ICH+PBS组（PBS组）和ICH+外泌体治疗组（EXO组），其中EXO组采用10 μg/mL hUC-MSCs-EXOs预处理2 h后，再利用160 μmol/L的氯高铁血红素刺激处理12 h。随后检测各组细胞炎症因子[肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6]的mRNA相对表达量、细胞活力、细胞凋亡程度，以及高迁移率族蛋白B1（HMGB1）核因子κB抑制蛋白α（IκBα）、核因子κB（NF-κB）等蛋白的相对表达量。

（1）hUC-MSCs-EXOs对ICH小鼠的作用：hUC-MSCs-EXOs显著减轻了ICH后小鼠脑组织的病理损伤和炎症细胞浸润。相较于Model组，EXO组小鼠术后3、7、14 d的mNSS评分及术后7 d的脑组织含水量、MDA含量均显著降低，SOD活性显著升高，差异均有统计学意义（P<0.05）。（2）hUC-MSCs-EXOs对ICH后BV2细胞的作用：相较于PBS组，EXO组TNF-α、IL-1β、IL-6的mRNA相对表达量、细胞早期凋亡水平、细胞内HMGB1和NF-κB的蛋白水平均显著降低，细胞活力、IκBα的蛋白水平均显著上升，差异均有统计学意义（P<0.05）。

hUC-MSCs-EXOs通过抑制HMGB1-NF-κB信号通路，减轻了ICH后的炎症反应和神经损伤，为ICH的治疗提供了新的潜在策略。

To investigate the effects and mechanisms of human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSCs EXOs) on inflammatory response and nerve damage after intracerebral hemorrhage (ICH).

(1) A total of 108 healthy male C57BL/6J mice were randomly divided into three groups: Sham group, Model group, and EXO group, with 36 mice in each group. The ICH model was established by stereotactic injection. The EXO group received a tail vein injection of 100 μg hUC-MSCs-EXOs in PBS solution 4 h after ICH surgery. Neurological function was evaluated using the modified neurological severity score (mNSS) on post-operative days 3, 7, and 14. On day 7 post-surgery, pathological morphological changes were observed via HE staining, and brain edema and oxidative stress indicators [malondialdehyde (MDA) content, total superoxide dismutase (SOD) activity] were detected. (2) An in vitro ICH model using BV2 cells was established and divided into three groups: Control group, PBS group, and EXO group. The EXO group was pre-treated with 10 μg/mL hUC-MSCs-EXOs for 2 h, followed by stimulation with 160 μmol/L hemin for 12 h. Subsequently, the relative mRNA expression level of inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6], cell viability, apoptosis rate, and relative protein expression level of high mobility group protein B1 (HMGB1), nuclear factor kappa B inhibitory protein alpha (IκBα), nuclear factor kappa B (NF-κB) were detected in each group.

(1) The effect of hUC-MSCs-EXOs on ICH mice: hUC-MSCs-EXOs significantly alleviated the pathological damage and inflammatory cell infiltration in the brain tissue of mice after ICH. Compared with the Model group, the mNSS scores of mice in the EXO group at 3, 7, and 14 d after surgery, as well as the brain tissue water content and MDA content at 7 d after surgery, were significantly reduced, while SOD activity was significantly increased, and the differences were statistically significant (P<0.05). (2) The effect of hUC-MSCs-EXOs on BV2 cells after ICH: Compared with the PBS group, the mRNA relative expression levels of TNF-α, IL-1β, and IL-6, early cell apoptosis levels, and protein levels of HMGB1 and NF-κB in the EXO group were significantly reduced. Cell viability and protein levels of IκBα were significantly increased, and the differences were statistically significant (P<0.05).

hUC-MSCs-EXOs alleviate inflammatory responses and neuronal damage after ICH by inhibiting the HMGB1-NF-κB signaling pathway, providing a new potential strategy for the treatment of ICH.