目的 探討鴉膽子苦醇調(diào)節(jié)環(huán)磷酸鳥苷-腺苷酸合成酶（cGAS）-干擾素基因刺激因子（STING）信號通路對肝癌H22荷瘤小鼠腫瘤生長及免疫功能的影響。方法 通過左前肢腋窩sc接種H22細胞建立荷瘤小鼠模型，隨機分為模型組，鴉膽子苦醇低、中、高劑量（0.916、1.832、3.664 mg·kg^-1，ig給藥）組，鴉膽子苦醇（3.664 mg·kg^-1，ig給藥）＋RU.521（5 mg·kg^-1，ip給藥）組。干預(yù)結(jié)束后，取胸腺、脾臟、腫瘤稱質(zhì)量，測定小鼠胸腺和脾臟指數(shù)、抑瘤率；T淋巴細胞轉(zhuǎn)化實驗檢測T淋巴細胞增殖指數(shù)；檢測巨噬細胞吞噬雞紅細胞的能力；收集血清，試劑盒法檢測白細胞介素-2（IL-2）、腫瘤壞死因子-α（TNF-α）水平；Western blotting法檢測腫瘤組織中cGAS、STING蛋白表達水平。結(jié)果 與對照組相比，模型組小鼠胸腺和脾臟指數(shù)、吞噬指數(shù)、吞噬百分率、T淋巴細胞增殖指數(shù)、IL-2和TNF-α水平顯著下降（P<0.05）；與模型組相比，鴉膽子苦醇低、中、高劑量組小鼠胸腺和脾臟指數(shù)、吞噬指數(shù)、吞噬百分率、T淋巴細胞增殖指數(shù)、IL-2和TNF-α水平、cGAS和STING蛋白表達顯著增加（P<0.05），瘤質(zhì)量顯著降低（P<0.05），且作用均呈現(xiàn)劑量相關(guān)性；與鴉膽子苦醇高劑量組相比，鴉膽子苦醇＋RU.521組胸腺和脾臟指數(shù)、吞噬指數(shù)、吞噬百分率、T淋巴細胞增殖指數(shù)、IL-2和TNF-α水平、cGAS和STING蛋白表達顯著下降（P<0.05），瘤質(zhì)量顯著增加（P<0.05）。結(jié)論 鴉膽子苦醇通過激活cGAS-STING信號通路抑制肝癌H22荷瘤小鼠腫瘤生長，增強其免疫功能。

Objective To investigate the impacts of brusatol on tumor growth and immune function of H22 hepatoma bearing mice by regulating the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene (STING) signal pathway. Methods The H22 tumor-bearing mice model was established by subcutaneous inoculation of H22 in the left forearm armpit. They were randomly grouped into model group, brusatol low, medium, high dose (0.916, 1.832, and 3.664 mg·kg^-1) group, and brusatol (3.664 mg·kg^-1) + cGAS inhibitor RU. 521 (5 mg·kg^-1) group. After the intervention, the thymus, spleen, and tumor were weighed, and the thymus and spleen indices and tumor inhibition rate of the mice were measured. Detection of T lymphocyte proliferation index using T lymphocyte transformation assay. Detect the ability of macrophages to engulf chicken red blood cells. Collect serum and detect interleukin-2 (IL-2) and tumor necrosis factor-α (TNF- α) using a kit method. Western blotting method was used to detect the expression levels of cGAS and STING proteins in tumor tissue. Results Compared with the control group, the thymus index, spleen index, phagocytic index, phagocytic percentage, proliferative index, the levels of IL-2 and TNF-α in the model group were significantly decreased (P< 0.05). Compared with the model group, the thymus index, spleen index, phagocytic index, phagocytic percentage, proliferative index, the levels of IL-2 and TNF- α, the expression of cGAS and STING in brusatol low, medium, high dose groups were significantly increased, the tumor weight was significantly decreased, and showed a dose-dependent relationship between groups (P< 0.05). Compared with brusatol high dose group, the thymus index, spleen index, phagocytic index, phagocytic percentage, proliferative index, the levels of IL-2 and TNF-α, the expression of cGAS and STING in brusatol high dose group + RU. 521 group were significantly decreased, the tumor weight were significantly increased (P< 0.05). Conclusion Brusatol can inhibit tumor growth and enhance immune function of H22 hepatoma bearing mice by activating cGAS-STING signal pathway.

R285.5

2020年度五官醫(yī)學(xué)院專項科研基金項目（2020WG07）