Tang Xiao-Fang, Liu Hai-Yan, Wu Ling, Li Min-Hui, Li Shu-Ping, Xu Hong-Bin
Obstetrics and Gynecology Department, Changzhou Second People's Hospital, Changzhou, China.
Obstetrics and Gynecology Department, Maternal and Child Health Care Hospital of Yancheng City, Yancheng, China.
Oncotarget. 2017 Nov 11;8(62):105703-105713. doi: 10.18632/oncotarget.22390. eCollection 2017 Dec 1.
In this study, oxygen glucose deprivation/re-oxygenation (OGDR) was applied to cultured endometrial cells to mimic ischemic-reperfusion injuries. We also tested the potential effect of Ginseng Rh2 (GRh2) against the process. In established T-HESC human endometrial cells and primary murine endometrial cells, GRh2 largely inhibited OGDR-induced viability reduction and cell death. Remarkably, OGDR induced programmed necrosis in the endometrial cells, evidenced by cyclophilin D-p53-adenine nucleotide translocator 1 (ANT-1) mitochondrial association, mitochondrial depolarization, reactive oxygen species production, and lactate dehydrogenase release. Notably, such effects by OGDR were largely attenuated with co-treatment of GRh2. Further, cyclophilin D inhibition or knockdown also protected endometrial cells from OGDR. On the other hand, forced over-expression of cyclophilin D facilitated OGDR-induced T-HESC cell necrosis, which was dramatically inhibited by GRh2. Together, GRh2 protects endometrial cells from OGDR possibly via inhibiting CypD-dependent programmed necrosis pathway.
在本研究中,采用氧糖剥夺/复氧(OGDR)处理培养的子宫内膜细胞,以模拟缺血再灌注损伤。我们还测试了人参皂苷Rh2(GRh2)对该过程的潜在作用。在已建立的T-HESC人子宫内膜细胞和原代小鼠子宫内膜细胞中,GRh2在很大程度上抑制了OGDR诱导的活力降低和细胞死亡。值得注意的是,OGDR诱导子宫内膜细胞发生程序性坏死,这通过亲环素D-p53-腺嘌呤核苷酸转位酶1(ANT-1)与线粒体的结合、线粒体去极化、活性氧产生以及乳酸脱氢酶释放得以证实。值得注意的是,GRh2的共同处理在很大程度上减弱了OGDR的这些作用。此外,亲环素D的抑制或敲低也保护子宫内膜细胞免受OGDR的影响。另一方面,亲环素D的强制过表达促进了OGDR诱导的T-HESC细胞坏死,而GRh2可显著抑制这种坏死。总之,GRh2可能通过抑制依赖亲环素D的程序性坏死途径来保护子宫内膜细胞免受OGDR的损伤。