【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(5×10⁴ cfu/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。更多还原

【Abstract】 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（5×10⁴ 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 of α-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 the spleen. The load of Salmonella enterica subsp. enterica serovar Typhimurium in the spleen of mice in the model group was significantly increased compared with that of the blank control group（P<0.05）, while the load of Salmonella enterica subsp. enterica serovar Typhimurium in the spleen of mice in the high, medium and low dose groups of Persicaria hydropiper was significantly lower than that of the model group（P<0.05）. The relative expression of interferon（IFN-α, IFN-β, IFN-γ）, IRF3, p-IRF3, p-TBK1 and STING proteins in the spleen of mice in the model group were significantly decreased compared with the blank control group（P<0.05）, while the relative expression of interferon（IFN-α, IFN-β, IFN-γ）, TBK1, p-TBK1, p-IRF3, cGAS and STING proteins were significantly higher（P<0.05）. The results suggested that Persicaria hydropiper had the effect of ameliorating immune damage in the spleen of Salmonella enterica subsp. enterica serovar Typhimurium-infected mice, and the mechanism of action might be achieved by upregulating the cGAS-STING pathway and thus inducing interferon production.更多还原