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目的:研究三七皂苷(PnS)对顺铂肾毒性的防护作用。方法:采用小鼠和原代兔肾近端小管细胞培养(FTC)建立体内外顺铂肾毒性模型。用双乙酰、苦味酸、溴乙锭、台酚蓝、~(125)碘标记和Fura 2-AM方法分别测血尿素氮、血清肌酐、细胞存活率、DNA链间交联、DNA-蛋白交联和细胞内游离钙离子。结果:预先2d给PnS(100,200mg·kg~(-1)·d~(-1))使顺铂导致的小鼠血尿素氮下降到83％和31％,血清肌酐下降到86％和42％(P<0.01)。提前24h PnS(10,100mg/L)与PTC孵育,细胞存活率从顺铂组的78％提高到81％和89％,DNA链间交联下降到47％和40％,DNA-蛋白交联下降到77％和42％,细胞内游离钙下降到70％和63％(P<0.01)。结论:PnS可预防顺铂的肾毒性,其机制是降低顺铂导致的DNA链间交联、DNA-蛋白交联和钙离子超载。
Objective: To study the protective effect of notoginsenoside (PNS) on nephrotoxicity of cisplatin. Methods: Mouse and primary rabbit renal proximal tubular cell culture (FTC) was used to establish cisplatin nephrotoxicity model in vitro and in vivo. Blood urea nitrogen, serum creatinine, cell survival rate, DNA strand cross-link, DNA-protein cross-linking were measured with diacetyl, picric acid, ethidium bromide, Combined with intracellular free calcium. Results: PnS (100, 200 mg · kg -1 · d -1) preconditioned for 2 days decreased the blood urea nitrogen of mice induced by cisplatin to 83% and 31%, and the serum creatinine dropped to 86% and 42% respectively % (P <0.01). PnS (10, 100 mg / L) was incubated with PTC 24 h earlier, and the cell viability increased from 78% to 81% and 89% in the cisplatin group. The DNA cross-linking decreased to 47% and 40% To 77% and 42%, intracellular free calcium dropped to 70% and 63% (P <0.01). CONCLUSION: PnS can prevent the nephrotoxicity of cisplatin by decreasing the cisplatin-induced DNA interchain cross-linking, DNA-protein cross-linking and calcium overload.