矢车菊-3-O-葡萄糖苷及其代谢物原儿茶酸对杂环胺诱导细胞损伤的修复机制

目的：研究矢车菊-3-O-葡萄糖苷（cyanidin-3-O-glucoside，C3G）及其主要代谢物原儿茶酸（protocatechuic acid，PCA）对杂环胺诱导细胞损伤的修复机制。方法：分别采用2-氨基-3-甲基咪唑并4,5-f]喹啉（2-amino-3-methylimidazo4,5-f]quinoline，IQ）和2-氨基-1-甲基-6-苯基-咪唑4,5-b]吡啶（2-amino-1-methyl-6-phenylimidazo4,5-b]pyridine，PhIP）诱导HepG2细胞损伤，利用细胞毒性实验（cell counting kit-8，CCK-8）、Hoechst33258染色法、流式细胞术和实时荧光定量聚合酶链式反应（quantitative polymerase chain reaction，qPCR）技术，评价C3G和PCA对杂环胺诱导损伤细胞的存活情况、细胞周期以及凋亡和DNA损伤关键基因表达的影响。结果：C3G和PCA能够显著提高杂环胺损伤细胞的存活率（P＜0.05），并使细胞发生S期阻滞。与IQ单独损伤组相比，C3G和PCA均可显著降低GADD45α和促凋亡基因Bim的mRNA水平，并显著提高抑凋亡基因Bcl-2和Bcl-xl的mRNA水平（P＜0.05）；与PhIP单独损伤组相比，C3G和PCA能够促进大多数促凋亡基因表达。结论：C3G和PCA能够通过减少DNA损伤和细胞凋亡修复IQ和PhIP诱导的细胞损伤，当细胞损伤严重至无法逆转时，可促进细胞凋亡，减少癌变。

Mechanism by Which Cyanidin-3-O-glucoside and Its Metabolite Protocatechuic Acid Repair Heterocyclic Aromatic Amines-induced Cell Damage

Objective: To study the potential mechanism of action of cyanidin-3-O-glucoside (C3G) and its main metabolite protocatechuic acid (PCA) in repairing heterocyclic aromatic amine-induced cell damage. Methods: 2-Amino-3-methylimidazolidine4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenyl-imidazole4,5-b]pyridine (PhIP) were used separately to induce cell damage to HepG2 cells. The cell counting kit-8 (CCK-8) assay, Hoechst33258 staining, flow cytometry and fluorescence quantitative polymerase chain reaction (qPCR) were used to evaluate the effects of C3G and PCA on the cell survival and cell cycle as well as the expression of key genes associated with cell apoptosis and DNA damage in heterocyclic aromatic amine-damaged cells. Results: C3G and PCA significantly increased the cell viability of heterocyclic aromatic amine-damaged HepG2 cells and induced S phase arrest. Compared with the IQ group, C3G and PCA significantly reduced the mRNA expression of GADD45α and the pro-apoptotic gene Bim, and increased the mRNA expression of the anti-apoptotic genes Bcl-2 and Bcl-xl (P < 0.05). Compared with the PhIP group, C3G and PCA could promote the expression of most pro-apoptotic genes. Conclusion: C3G and PCA can repair cell damage induced by IQ and PhIP through reducing DNA damage and cell apoptosis. However, when cell damage is too severe to be reversed, they can instead promote cell apoptosis, thus reducing canceration.