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目的:探讨白藜芦醇(RES)在阿霉素(DOX)所致淋巴瘤裸鼠动脉内皮细胞凋亡中的拮抗作用及相关机制。方法:给30只雄性Balb/c裸鼠经皮下接种Raji细胞建立淋巴瘤模型并随机分成3组,即对照组、DOX组和DOX+RES组,每组10只(n=10)。用分光光度法测定颈动脉组织中半胱氨酸蛋白酶3(Caspase 3)的活性。用免疫组化染色法检测颈动脉组织中诱导型一氧化氮合酶(iNOS)、Bcl-2和Bax的表达。应用TUNEL方法检测颈动脉内皮细胞的凋亡。分别予以Western blot和硝酸还原酶方法检测淋巴瘤裸鼠颈动脉组织中iNOS蛋白的表达和血清中NO的含量。结果:与DOX组相比较,DOX+RES组颈动脉组织中iNOS的表达下调(P<0.05),血清NO的含量减少(P<0.01),Bcl-2的表达升高(P<0.01),Bax的表达降低(P<0.01),Caspase 3的活性明显降低(P<0.01),颈动脉内皮细胞凋亡的数量明显减少(P<0.01)。DOX+RES组和DOX组的移植肿瘤的体积无明显差异。结论:RES对于DOX所致淋巴瘤裸鼠动脉内皮细胞凋亡具有拮抗作用,其作用机制可能涉及抑制iNOS/NO途径。
AIM: To investigate the antagonistic effect of resveratrol (ADR) on the apoptosis of arterial endothelial cells (AECs) induced by doxorubicin (DOX) in nude mice and its related mechanisms. Methods: Thirty male Balb / c nude mice were inoculated subcutaneously with Raji cells to establish a lymphoma model and randomly divided into three groups: control group, DOX group and DOX + RES group, with 10 in each group (n = 10). The activity of Caspase 3 in carotid artery was measured by spectrophotometry. The expression of inducible nitric oxide synthase (iNOS), Bcl-2 and Bax in carotid artery was detected by immunohistochemistry. TUNEL method was used to detect the apoptosis of carotid artery endothelial cells. Western blot and nitrate reductase method were used to detect the expression of iNOS protein and NO in serum of carotid artery of nude mice. Results: Compared with DOX group, the expression of iNOS in the carotid artery of DOX + RES group was down-regulated (P <0.05), the content of NO was decreased (P <0.01) and the expression of Bcl-2 was increased Bax decreased (P <0.01), Caspase 3 activity decreased significantly (P <0.01), and the number of carotid artery endothelial cells decreased significantly (P <0.01). There was no significant difference in the volume of tumor transplanted between DOX + RES group and DOX group. Conclusion: RES can antagonize the apoptosis of arterial endothelial cells in nude mice with DOX. The mechanism may be related to the inhibition of iNOS / NO pathway.