辣蓼上调cGAS-STING信号通路改善鼠伤寒沙门氏菌感染小鼠的脾脏免疫损伤  

Upregulation of cGAS-STING signaling pathway mediated by Persicaria hydropiper improved spleen immune damage in mice infected with Salmonella enterica subsp.enterica serovar Typhimurium

作　　者：刘涵笑 张易安 郭琰娜 梁少姗 丁康宁 卢梦涵 唐陆平[1] 何永明[1] LIU Hanxiao;ZHANG Yian;GUO Yanna;LIANG Shaoshan;DING Kangning;LU Menghan;TANG Luping;HE Yongming(Department of Veterinary Medicine,Foshan University,Foshan 528225,China)

机构地区：[1]佛山科学技术学院动物医学系,广东佛山528225

出　　处：《黑龙江畜牧兽医》2023年第4期110-116,133,共8页Heilongjiang Animal Science And veterinary Medicine

基　　金：广东省科技计划项目(2015A040404048);广东省农业农村厅项目(2023KJ119);广东省教育厅项目(2017GCZX006)。

摘　　要：为了探究辣蓼水提液对鼠伤寒沙门氏菌感染小鼠脾脏免疫损伤的保护作用及其潜在机制,试验将48只健康、体重接近的SPF级雌性Balb/c小鼠随机分为6组,分别为空白对照组、模型组、阳性药物组及辣蓼高、中、低剂量组,每组8只。空白对照组和模型组灌胃PBS,阳性药物组每天按体重灌胃给予庆大霉素20 mg/kg,辣蓼高、中、低剂量组分别灌胃给予20,10,5 g/kg的辣蓼水提液,小鼠给药体积为按体重0.2 mL/10 g,连续给药8 d。给药2 d后,除空白对照组外其余组小鼠均灌胃LD50(5×104cfu/mL)鼠伤寒沙门氏菌0.2 mL,末次给药后禁食不禁水12 h,麻醉小鼠安乐死后取脾脏组织进行组织病理学检查、鼠伤寒沙门氏菌负荷量测定,以及α-干扰素(IFN-α)、β-干扰素(IFN-β)、γ-干扰素(IFN-γ)、干扰素调节因子3(IRF3)、磷酸化干扰素调节因子3(p-IRF3)、TANK结合激酶1(TBK1)、磷酸化TANK结合激酶1(p-TBK1)、干扰素刺激基因(STING)与环腺苷酸鸟苷酸合成酶(cGAS)蛋白相对表达量的检测。结果表明:模型组小鼠脾脏结构不清晰,红髓、白髓分辨不清,增生明显,有炎性细胞浸润,出血、渗出物明显;而辣蓼高、中、低剂量组小鼠脾脏均无明显病理变化,减轻了脾脏组织病理学损伤。模型组小鼠脾脏中鼠伤寒沙门氏菌负荷量较空白对照组显著增加(P<0.05),而辣蓼高、中、低剂量组小鼠脾脏中鼠伤寒沙门氏菌负荷量显著低于模型组(P<0.05)。模型组小鼠脾脏干扰素(IFN-α、IFN-β、IFN-γ)、IRF3、p-IRF3、p-TBK1与STING蛋白相对表达量较空白对照组均显著下降(P<0.05);而与模型组比较,辣蓼高、中剂量组干扰素(IFN-α、IFN-β、IFN-γ)、TBK1、p-TBK1、p-IRF3、cGAS和STING蛋白相对表达量均显著升高(P<0.05)。说明辣蓼具有改善鼠伤寒沙门氏菌感染小鼠脾脏免疫损伤的作用,作用机理可能是通过上调cGAS-STING通路从而诱导干扰素产生而得以实现。In order to explore the protective effects and its potential mechanism of aqueous extracts of Persicaria hydropiper against spleen immune damage in mice infected with Salmonella enterica subsp.enterica serovar Typhimurium,in the experiment,48 healthy,SPF-grade female Balb/c mice of close body weights were randomly divided into six groups:blank control group,model group,positive drug group and Persicaria hydropiper high,medium and low dose groups;there were eight mice in each group.The blank control group and model group were given PBS by gavage,the positive drug group was given gentamicin 20 mg/kg per day by gavage according to body weight,and Persicaria hydropiper high,medium and low dose groups were given 20,10 and 5 g/kg of Persicaria hydropiper aqueous extracts by gavage respectively;the mice were given 0.2 mL/10 g according the body weight in a continuous volume for 8 d.After 2 d of administration,mice in all groups except the blank control group were gavaged with 0.2 mL of LD50(5×10~4 cfu/mL)of Salmonella enterica subsp.enterica serovar Typhimurium.After the last administration,mice were fasted and water was free for 12 h;after euthanasia of anesthetized mice,spleen tissue was taken for histopathological examination,Salmonella enterica subsp.enterica serovar Typhimurium load examination,and the determination of the relative expression ofα-interferon(IFN-α),β-interferon(IFN-β),γ-interferon(IFN-γ),interferon regulator 3(IRF3),phosphorylated interferon regulator 3(p-IRF3),TANK-binding kinase 1(TBK1),phosphorylated TANK-binding kinase 1(P-TBK1),interferon-stimulating gene(STING)and cyclic adenylate guanylate synthetase(cGAS)protein.The results showed that the mice in the model group had indistinct spleen structure,indistinguishable red and white marrow,obvious hyperplasia,inflammatory cell infiltration and obvious hemorrhagic exudate.No significant pathological changes in the spleen of mice in the high,medium and low dose groups of Persicaria hydropiper,which attenuated the histopathological damage to th

关 键 词：辣蓼 鼠伤寒沙门氏菌 脾脏 干扰素 TANK结合激酶1 

分 类 号：S853.7[农业科学—临床兽医学]