【摘要】：目的研究新型一氧化氮(NO)供體O~2-(2,4-二硝基苯基)1-[(4-乙氧羰基)哌嗪-1-yl]偶氮-1-摀-1,2-二醇(JS-K)對H22荷瘤小鼠腫瘤能量代謝的調節(jié)作用。方法 BALB/c小鼠皮下接種H22細胞建立荷瘤小鼠模型,并隨機分為模型組、氟尿嘧啶(5-FU)組、JS-K 0.75和1.50 mg·kg~(-1)組。JS-K組和模型組小鼠每3 d尾靜脈注射不同劑量JS-K或生理鹽水,連續(xù)14 d(共給藥5次);5-FU組每天1次ip給予5-FU 20 mg·kg~(-1),給藥后第15天將小鼠處死,分離胸腺、脾和完整瘤體,并稱取其質量,計算抑瘤率和臟器系數、比色法檢測瘤組織中已糖激酶(HK)、丙酮酸激酶(PK)、磷酸果糖激酶(PFK)、琥珀酸脫氫酶(SDH)和腺苷三磷酸酶(ATPase)活性,以及乳酸和ATP水平;Western蛋白印跡法檢測各組瘤組織中缺氧誘導因子-1α(HIF-1α)和己糖激酶Ⅱ(HKⅡ)蛋白表達。結果與模型組比較,JS-K0.75和1.50mg·kg~(-1)組瘤質量顯著下降(P0.01),抑瘤率分別為23.9%和50.3%JS-K 0.75和1.50 mg·kg~(-1)組小鼠胸腺系數和脾系數與模型組無明顯差異比色法檢測結果顯示,JS-K 1.50 mg·kg~(-1)組瘤組織中HK,PFK,SDH,PK和ATPase活性較模型組的[22.6±3.7,14.4±2.6,(10.5±2.6)U·g~(-1)蛋白,(12.9±3.2)kU·g~(-1)蛋白和(0.70±0.10)mmolPi·g~(-1)蛋白·h~(-1)]分別下降了42.0%,26.6%,23.3%,22.7%和21.7%(P0.01,P0.05);JS-K 1.50 mg·kg~(-1)組瘤組織中ATP水平較模型組下降16.6%(P0.01);JS-K0.75和1.50mg·kg~(-1)組瘤組織中乳酸水平較模型組分別下降38.7%和59.4%(P0.01)。Western蛋白印跡檢測結果顯示,與模型組比較,JS-K 1.50 mg·kg~(-1)組瘤組織中HIF-1α(蛋白表達顯著降低(P0.01);JS-K 0.75和1.50 mg·kg~(-1)組HKⅡ蛋白表達均顯著降低(P0.05,P0.01)。結論 JS-K能抑制H22荷瘤小鼠腫瘤生長,其機制可能與抑制糖酵解和有氧氧化途徑從而調節(jié)腫瘤能量代謝有關。
[Abstract]:Objective to study the effect of a new nitric oxide (NO) donor, Of2- (2H2-dinitrophenyl) 1- [(4-ethoxycarbonyl) piperazine-1-yl] azo-1-fu-1- 2-diol (JS-K) on tumor energy of H22 tumor-bearing mice. The regulation of metabolism. Methods BALB/c mice were inoculated subcutaneously with H22 cells to establish tumor-bearing mice model, and were randomly divided into model group, fluorouracil (5-FU) group. JS-K 0.75 and 1.50 mg kg~ (-1) groups. Mice in JS-K group and model group were injected with different doses of JS-K or normal saline every 3 days for 14 days (5 times). 5-FU group was given 5-FU 20 mg kg~ (-1) once a day. The mice were killed on the 15th day, thymus, spleen and complete tumor were separated, and the tumor inhibition rate and organ coefficient were calculated. The activities of hexokinase (HK), pyruvate kinase (competitive), phosphofructokinase (PFK), succinate dehydrogenase (SDH) and adenosine triphosphatase (ATPase), as well as the levels of lactic acid and ATP were detected by colorimetric method. The expression of hypoxia inducible factor-1 偽 (HIF-1 偽) and hexokinase 鈪，

本文編號：2314001