目的 研究大黄素通过调节环鸟苷单磷酸腺苷合成酶（cGAS）/干扰素基因刺激蛋白（STING）信号通路对细菌性脑膜炎大鼠神经炎症的影响。方法 将60只大鼠按照随机数字表法分为对照组、模型组、大黄素组、青霉素组、大黄素＋SR-717组，每组12只。除对照组外的4组大鼠采用立体定向仪向大脑中注射B族溶血性链球菌（GBS）菌液的方法构建细菌性脑膜炎大鼠模型，造模成功后，大黄素组ip 20 mg/kg大黄素，青霉素组ip 10 mL/kg青霉素，大黄素＋SR-717组大鼠ip 20 mg/kg大黄素及30 mg/kg SR-717，对照组和模型组大鼠注射等量生理盐水。给药3 d后，进行神经系统症状评分和脑脊液白细胞（WBC）计数；以苏木精–伊红（HE）染色检测脑组织病理学变化；以酶联免疫吸附（ELISA）法检测大鼠脑组织中白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）含量；以TUNEL染色法检测大鼠脑皮层神经细胞凋亡；以Western blotting检测大鼠脑组织cGAS、STING蛋白相对表达量。结果 与模型组比较，大黄素组大鼠神经系统症状评分、脑脊液WBC数量、脑组织中IL-6、TNF-α含量、TUNEL染色神经细胞数、cGAS及STING蛋白相对表达量均显著降低（P＜0.05），脑组织损伤明显减轻；与大黄素组比较，大黄素＋SR-717组大鼠神经系统症状评分、脑脊液WBC数量、脑组织中IL-6、TNF-α含量、TUNEL染色神经细胞数、cGAS及STING蛋白相对表达量显著增加（P＜0.05），脑组织损伤再次加重。结论 大黄素可能通过抑制cGAS/STING信号通路减轻细菌性脑膜炎大鼠的神经炎症。

Objective To investigate emodin affect the neuroinflammation of bacterial meningitis rats by regulating cGAS/STING signaling pathway. Methods According to random number table method, 60 rats were divided into control group, model group, emodin group, penicillin group, emodin + SR-717 group, with 12 rats in each group. The bacterial meningitis rat model was established by injecting B group hemolytic streptococcus (GBS) bacteria solution into the brain with stereotactic apparatus in 4 groups except control group. After the model was successfully made, rats in emodin group were ip with 20 mg/kg emodin, rats in penicillin group were ip with 10 mL/kg penicillin, rats in emodin + SR-717 group were ip with 20 mg/kg emodin and 30 mg/kg SR-717. The rats in control and model group were injected with the same amount of normal saline. The neurological symptoms score amd cerebrospinal fluid white blood cell (WBC) count were performed 3 d after administration. HE staining was applied to detect pathological changes in brain tissue, ELISA was applied to detect the content of IL-6 and TNF-α in brain tissue; the apoptosis of rat cortical neurons was detected by TUNEL staining. Western blotting was applied to detect the expression of cGAS and STING relative protein expression in brain tissue. Results Compared with the model group, the neurological symptom score, WBC count in cerebrospinal fluid, content of IL-6 and TNF-α in brain tissue, number of TUNEL stained nerve cells, protein expression of cGAS and STING relative protein expression in the emodin group were significantly decreased (P< 0.05), brain tissue damage wes obviously reduced. Compared with emodin group, the neurological symptom score, WBC count in cerebrospinal fluid, content of IL-6 and TNF-α in brain tissue, number of TUNEL stained nerve cells, protein expression of cGAS and STING relative protein expression in emodin + SR-717 group were significantly increased (P< 0.05), brain tissue damage worsened again. Conclusion Emodin may reduce neuroinflammation in bacterial meningitis rats by inhibiting the cGAS/STING signaling pathway.

R285;R286.1

开封市科技发展计划项目（2203060）