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Pharmacy Information 2024
阻断SP/NK1R信号轴可抑制小鼠黑色素瘤增殖
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Abstract:
目的：探讨阻断SP/NK1R信号轴对小鼠黑色素瘤生长的影响及可能作用途径。方法：建立瞬时接种B16F10细胞形成原位黑色素瘤的小鼠模型，腹腔注射给予NK1R拮抗剂阿瑞匹坦(5 mg/kg)进行干预。给药5次后取小鼠胸腺、脾脏和皮肤黑色素瘤组织，计算各组小鼠体重变化、肿瘤增长变化、胸腺指数和脾脏指数；采用免疫荧光染色考察黑色素瘤组织中细胞增殖和凋亡情况；并观察肿瘤组织中浸润效应CD8 T细胞的表达情况。结果：给予阿瑞匹坦拮抗NK1R对各组小鼠体重没有明显影响，但能显著抑制原位黑色素瘤的增殖；阻断SP/NK1R信号轴能够引起小鼠胸腺指数显著升高，但对脾脏指数没有明显影响；免疫荧光染色结果显示给予阿瑞匹坦能够显著抑制黑色素瘤细胞在体内的增殖，并显著促进其凋亡；同时，拮抗NK1R能够显著增加肿瘤浸润效应CD8 T细胞的数目。结论：阻断SP/NK1R信号轴可以显著抑制小鼠中黑色素瘤细胞的增殖，并促进肿瘤细胞凋亡，这一作用可能是通过促进CD8 T细胞浸润，增强抗肿瘤免疫来实现的。
Object: Investigate the effect of blocking the SP/NK1R signal axis on the growth of melanoma in mice and its possible pathway. Methods: A mouse model of in situ melanoma formation by transient inoculation of B16F10 was established, and the NK1R antagonist aprepitant (5 mg/kg) was given intraperitoneally for intervention. Thymus, spleen, and skin melanoma tissues were taken from mice after 5 administrations, and body weight changes, tumor growth changes, thymus index, and spleen index were calculated for each group. Cell proliferation and apoptosis in melanoma tissues were examined by immunofluorescence staining. The expression of infiltrating CD8 T cells in tumor tissues was observed. Results: Administration of aprepitant to antagonize NK1R had no significant effect on the body weight of mice in all groups, but significantly inhibited the proliferation of in situ melanoma. Blocking the SP/NK1R signal axis can significantly increase the thymus index, but has no significant effect on the spleen index. Immunofluorescence staining showed that aprepitant could significantly inhibit the proliferation of melanoma cells in vivo and promote their apoptosis. At the same time, antagonizing NK1R can significantly increase the number of CD8 T cells with a tumor invasion effect. Conclusion: Blocking the SP/NK1R signaling axis can significantly inhibit the proliferation of melanoma cells in tumor-bearing mice and promote tumor cell apoptosis, which may be achieved by promoting CD8 T cell infiltration and enhancing anti-tumor immunity.
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