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目的研究坏死性凋亡特异性抑制剂(Nec-1)抗环孢素A致坏死性凋亡的机制。方法将30只C57/BL6雄性小鼠随机分为对照组、环孢素A组、Nec-1组,对照组给予橄榄油口服,环孢素A组以100 mg/(kg·d)灌胃给予环孢素A,Nec-1组在给予环孢素A前0.5 h采取腹腔注射方式给予Nec-1 2.5 mg/kg。14 d后测定小鼠血液肌酐(SCr)、尿素氮(BUN)含量变化,皮质中还原型谷胱甘肽(GSH)活性变化,丙二醛(MDA)含量变化;检测皮质中受体连接蛋白(RIP3)表达。结果处理后14 d,与对照组比较,环孢素A组能使血清中SCr及BUN水平明显升高,皮质中GSH活性下降,丙二醛(MDA)水平升高;与环孢素A组比较,Nec-1组SCr及BUN水平明显下降,GSH活性增加,丙二醛含量下降(P<0.05),但3组小鼠皮质中RIP3表达无明显差异。结论 Nec-1对环孢素A肾毒性具有保护作用,表明环孢素A肾毒性可能与坏死性凋亡有关。
Aim To study the mechanism of necrotizing apoptosis-specific inhibitor (Nec-1) against necrotic apoptosis of cyclosporine. Methods Thirty C57 / BL6 male mice were randomly divided into control group, cyclosporin A group and Nec-1 group. The control group was orally administered with olive oil. The cyclosporin A group was given orally at 100 mg / (kg · d) For cyclosporin A and Nec-1 groups, Nec-1 2.5 mg / kg was intraperitoneally injected 0.5 h before cyclosporine A administration. The levels of blood creatinine (SCr) and blood urea nitrogen (BUN), catalase (GSH) and cortisol (MDA) (RIP3) expression. Results Serum levels of SCr and BUN were significantly increased in ciclosporin A group and GSH activity in cortex were decreased and malondialdehyde (MDA) level was increased on the 14th day after treatment compared with the control group. Compared with the Nec-1 group, the levels of SCr and BUN were significantly decreased, the activity of GSH was increased and the content of malondialdehyde was decreased (P <0.05). However, the expression of RIP3 in Nec-1 group was not significantly different. Conclusion Nec-1 has a protective effect against cyclosporin A nephrotoxicity, indicating that cyclosporin A nephrotoxicity may be related to necrotic apoptosis.