土槿皮乙酸通过DNA损伤反应诱导细胞自噬来抑制凋亡

Pseudolaric acid B induced autophagy through DNA damage response to inhibit apoptosis

目的本课题在人肺成纤维细胞MRC5中研究土槿皮乙酸(PAB)诱导的DNA损伤反应、自噬及其与凋亡的关系。方法以4 mmol/L PAB分别处理12、24、36、48 h后,Western blot分析DNA损伤反应标志蛋白g-H2AX表达;通过酰尸胺染色法、Western blot法确定PAB是否诱导细胞自噬;通过抑制DNA损伤反应的发生确定DNA损伤反应对自噬和凋亡的影响。结果 PAB诱导DNA损伤反应;PAB诱导细胞自噬;抑制DNA损伤反应抑制细胞自噬并促进细胞凋亡。结论 PAB通过诱导DNA损伤反应诱导细胞自噬,抑制自噬促进细胞凋亡并增加PAB的抑制率。

Objective To investigate the relationship of pseudolaric acid B （PAB）-inducing DNA damage response, autophagy and apoptosis in human fibroblasts MRC5. Methods After 4 mmol/L PAB treatment of 12,24,36,48 h, expression of g-H2AX that was the marker of DNA damage response was analysed by Western blot; MDC staining and Western blot was used to determine whether PAB could induce autophagy; To determine the effects of DNA damage on autophagy and apoptosis by inhibiting the occurrence of DNA damage. Results PAB activated DNA damage response; PAB induced autophagy; Inhibits DNA damage inhibits autophagy and promotes apoptosis. Conclusion PAB induced autophagy through DNA damage response, inhibited autophagy and promoted cell apoptosis, and increased the inhibitory ratio of PAB.