Page 41 - 南京医科大学学报自然科学版

第43卷第7期 南京医科大学学报（自然科学版）
2023年7月 Journal of Nanjing Medical University（Natural Sciences） ·927 ·

·基础研究·

脑膜淋巴管转运功能障碍加重脂多糖诱导的小鼠中枢炎症

谢 雯，董洪权，侍崇龙，金文杰 *
南京医科大学第一附属医院麻醉科，江苏 南京 210029

［摘 要］ 目的：探讨脑膜淋巴管（meningeal lymphatic vessel，mLV）转运功能障碍对脂多糖（lipopolysaccharide，LPS）诱导的小
鼠中枢神经系统炎症的影响。方法：①16只C57BL/6雄性小鼠随机分为4组，Control组腹腔注射生理盐水，LPS组分别腹腔注
射LPS（2 mg/kg）12、24、72 h，而后观察小鼠mLV转运功能、海马区小胶质细胞（microglial，MG）活化、白介素（interleukin，IL）⁃6
和IL⁃1β水平。②将8只小鼠随机分为2组，分别为Control组和VEGFR3抑制剂MAZ51组，观察MAZ51对mLV转运功能的影
响。③将24只小鼠分为4组，分别为Control组、MAZ51组、LPS组、LPS+MAZ51组，对MAZ51组和LPS+MAZ51组预先腹腔注射
MAZ51（10 mg/kg），每周5 d，共30 d，6周后对LPS组和LPS+MAZ51组注射LPS，1 d后行为学实验评估小鼠的逃避恐惧能力；免
疫组化检测 MG 活化情况；ELISA 法检测 IL⁃6、IL⁃1β的表达量。结果：小鼠腹腔注射 LPS 24 h 后脑膜 LYVE⁃1 面积和颈深淋
巴结内 OVA⁃647 面积明显减少（P < 0.01），72 h 内均低于基础水平（P < 0.01），24 h 后海马 MG 活化、IL⁃6 和 IL⁃1β均明显增加
（P < 0.01）。与Control组相比，MAZ51组OVA⁃647荧光面积显著减少（P < 0.01）。LPS组小鼠海马区MG活化和IL⁃6、IL⁃1β的
表达相对Control组均明显增加（P < 0.01）且小鼠僵直时间明显降低（P < 0.01）；与LPS组相比，LPS+MAZ51组小鼠海马区MG
活化和炎症因子的表达均增加（P < 0.01）且僵直时间明显减少（P < 0.01）。结论：mLV转运障碍通过增加炎性介质聚积，活化
MG，加重LPS诱导的小鼠中枢炎症和认知功能障碍。
［关键词］ 脑膜淋巴管；小胶质细胞；白介素⁃6；白介素⁃1β；MAZ51；脂多糖
［中图分类号］ R512.3 ［文献标志码］ A ［文章编号］ 1007⁃4368（2023）07⁃927⁃07
doi：10.7655/NYDXBNS20230705

Meningeal lymphatic vessel transport dysfunction exacerbates LPS⁃induced central inflam⁃
mation in mice

XIE Wen，DONG Hongquan，SHI Chonglong，JIN Wenjie *
Department of Anesthesiology，the First Affiliated Hospital of Nanjing Medical University，Nanjing 210029，China

［Abstract］ Objective：To explore the effects of meningeal lymphatic vessel transport dysfunction on lipopolysaccharide（LPS）⁃induced
central nervous system inflammation in mice. Methods：Firstly，sixteen C57BL/6 mice were randomly divided into four groups，
normal saline was injected intraperitoneally in the Control group. The LPS groups were injected intraperitoneally with LPS（2 mg/kg），
and then the transport function of meningeal lymphatic vessels，activation of microglia and levels of interleukin⁃6（IL⁃6）and interleukin⁃1β
（IL⁃1β）in the hippocampus were observed after 12 h，24 h and 72 h. Secondly，eight mice were randomly assigned to two groups：
Control group and VEGFR3 inhibitor MAZ51 group，to observe the effects of MAZ51 on the transport function of meningeal lymphatic
vessels. Finally，twenty⁃four mice were divided into four groups as follows：control group，MAZ51 group，LPS group，and LPS+MAZ51
group. MAZ51（10 mg/kg）was preinjected intraperitoneally into MAZ51 group and LPS+MAZ51 group for five days per week with a
total of 30 days. After six weeks，LPS was injected into LPS group and LPS+MAZ51 group. A day later，behavioral experiments that
assess the ability of mice to escape from fear were conducted；the activation of microglia in the hippocampus was measured by
immunohistochemistry；the expression of IL⁃6 and IL⁃1β was evaluated by ELISA method. Results：The area of LYVE⁃1 in meninges
and the area of OVA⁃647 in the deep cervical lymph nodes were significantly decreased 24 h after intraperitoneal injection of LPS（P <
0.01），and were lower than the basal level for 72 h（P < 0.01）. The activation of microglia and levels of IL⁃ 6 and IL⁃1β in the
hippocampus were significantly increased after 24 h（P < 0.01）. Compared with the control group，the area of OVA⁃647 fluorescence in
the MAZ51 group was significantly reduced（P < 0.01）. The activation of microglia and the expression of inflammatory factors in the

［基金项目］ 江苏省自然科学基金青年基金（BK20171088）
∗
通信作者（Corresponding author），E⁃mail：kinwj210@126.com