目的 研究大黃素通過調(diào)節(jié)環(huán)鳥苷單磷酸腺苷合成酶（cGAS）/干擾素基因刺激蛋白（STING）信號通路對細(xì)菌性腦膜炎大鼠神經(jīng)炎癥的影響。方法 將60只大鼠按照隨機(jī)數(shù)字表法分為對照組、模型組、大黃素組、青霉素組、大黃素＋SR-717組，每組12只。除對照組外的4組大鼠采用立體定向儀向大腦中注射B族溶血性鏈球菌（GBS）菌液的方法構(gòu)建細(xì)菌性腦膜炎大鼠模型，造模成功后，大黃素組ip 20 mg/kg大黃素，青霉素組ip 10 mL/kg青霉素，大黃素＋SR-717組大鼠ip 20 mg/kg大黃素及30 mg/kg SR-717，對照組和模型組大鼠注射等量生理鹽水。給藥3 d后，進(jìn)行神經(jīng)系統(tǒng)癥狀評分和腦脊液白細(xì)胞（WBC）計(jì)數(shù)；以蘇木精–伊紅（HE）染色檢測腦組織病理學(xué)變化；以酶聯(lián)免疫吸附（ELISA）法檢測大鼠腦組織中白細(xì)胞介素-6（IL-6）、腫瘤壞死因子-α（TNF-α）含量；以TUNEL染色法檢測大鼠腦皮層神經(jīng)細(xì)胞凋亡；以Western blotting檢測大鼠腦組織cGAS、STING蛋白相對表達(dá)量。結(jié)果 與模型組比較，大黃素組大鼠神經(jīng)系統(tǒng)癥狀評分、腦脊液WBC數(shù)量、腦組織中IL-6、TNF-α含量、TUNEL染色神經(jīng)細(xì)胞數(shù)、cGAS及STING蛋白相對表達(dá)量均顯著降低（P＜0.05），腦組織損傷明顯減輕；與大黃素組比較，大黃素＋SR-717組大鼠神經(jīng)系統(tǒng)癥狀評分、腦脊液WBC數(shù)量、腦組織中IL-6、TNF-α含量、TUNEL染色神經(jīng)細(xì)胞數(shù)、cGAS及STING蛋白相對表達(dá)量顯著增加（P＜0.05），腦組織損傷再次加重。結(jié)論 大黃素可能通過抑制cGAS/STING信號通路減輕細(xì)菌性腦膜炎大鼠的神經(jīng)炎癥。

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

開封市科技發(fā)展計(jì)劃項(xiàng)目（2203060）