DHA对人肝癌细胞增殖与凋亡的影响及其机制的研究

目的：探讨二十二碳六烯酸（DHA）对人肝癌细胞株Bel-7402增殖和凋亡的影响及其机制。方法：用不同浓度的DHA（0,25,50,100,200 μmol/L）分别作用人肝癌Bel-7402细胞24,48,72 h后,用MTT法检测细胞的增殖情况、Western blot检测Bcl-2和Bax蛋白的表达,并分别用流式细胞仪、real-time PCR和caspase-3活性检测试剂盒检测上述梯度浓度的DHA作用 Bel-7402细胞48 h后的凋亡情况、Bim基因表达和caspase-3活性。结果：不同浓度、不同时间DHA作用后,Bel-7402细胞增殖明显抑制,呈浓度和时间依赖性（均P<0.05）;细胞Bax蛋白表达增加、Bcl-2蛋白表达降低,呈明显浓度依赖性（均P<0.05）,但无明显时间依赖性（均P>0.05）。不同浓度DHA作用48 h后,Bel-7402细胞凋亡率、Bim基因表达和caspase-3的活性均明显增加,且均呈浓度依赖性（均P<0.05）。结论：DHA可抑制人肝癌Bel-7402细胞的增殖并诱导细胞凋亡,其机制可能与激活线粒体凋亡通路有关。     

完全性葡萄胎绒毛凋亡与基因表达的相关研究

目的 :探讨完全性葡萄胎绒毛凋亡、增殖活性与 Bcl-2、Bax、Fas、Fas-L及增殖细胞核抗原 ( PCNA)基因表达的相关性。方法 :收集正常早孕绒毛标本及近一年归档的完全性葡萄胎绒毛蜡块 ,原位末端标记法 ( TUNEL)进行细胞凋亡的组织学检测 ,免疫组织化学法测定 Bcl-2、Bax、Fas、Fas-L、PCNA的分布与含量 ,原位杂交法测定 Fas、Fas-Lm RNA的分布与含量。结果 :正常早孕绒毛有少量凋亡细胞 ,主要分布于合体滋养细胞 ,Bcl-2、PCNA蛋白仅在细胞滋养细胞表达且含量丰富 ,Bax、Fas、Fas-L蛋白在合体滋养细胞表达且含量低下。完全性葡萄胎绒毛合体滋养细胞凋亡较正常早孕明显增多 ,Fas、Fas-L 蛋白及其 m RNA不仅在合体滋养细胞而且在细胞滋养细胞表达均明显增强 ,Bcl-2、Bax蛋白在两种细胞中表达也增强 ;PCNA蛋白仅见于细胞滋养细胞 ,含量丰富。结论 :完全性葡萄胎绒毛凋亡细胞增多 ,主要经 Fas/ Fas-L 转录与翻译水平介导 ,表现为高凋亡与高增殖共存现象 ,可能与其无控生长的特性相关。     

过表达Tg737基因对肝癌细胞周期和凋亡的影响

目的:探讨Tg737基因过表达对人肝癌细胞株细胞周期和凋亡的影响及可能的机制。方法:将肝癌HepG2和MHCC97-H细胞分别用脂质体法转染pcDNA3.1-Tg737质粒(Tg737过表达组)或pcDNA3.1空载体(空载体组),或单纯脂质体孵育(脂质体组),以各自未处理的细胞为空白对照。48h后分别用流式细胞仪检测细胞周期与凋亡,Hoechst33342染料法检测细胞核形态,Westernblot法检测cyclinA、Bax、Bcl-2表达。结果:与各自的空白对照组比较,Tg737过表达组HepG2和MHCC97-H细胞的S期细胞数量与细胞凋亡率均明显增加(均P0.05),且细胞核均出现明显凋亡形态学改变,同时伴随cyclinA、Bax的表达上调和Bcl-2的下调(均P0.05);空载体组、脂质体组HepG2和MHCC97-H细胞镜下未见明显的凋亡形态学变化,且上述指标差异均无统计学意义(均P0.05)。结论:Tg737基因过表达可以抑制肝癌细胞周期进程、促进其凋亡,机制可能与Tg737参与调节cyclinA、Bax、Bcl-2有关的信号通路有关。     

表达人端粒酶逆转录酶小干扰RNA的增殖腺病毒对肝癌细胞的抑制作用

目的 观察表达人端粒酶逆转录酶小干扰RNA(hTERT-siRNA)的增殖腺病毒(ZD-hTERT)对人肝癌Bel-7402细胞增殖及凋亡影响.方法 ZD-hTERT、增殖腺病毒ZD-EGFP、表达hTERT-siRNA的增殖缺陷腺病毒Ad-hTERT、增殖缺陷腺病毒Ad-EGFP分别感染人肝癌Bel-7402细胞.Western blot法检测ElA表达;逆转录-聚合酶链反应(RT-PCR)、Western blot法检测hTERT表达;噻唑蓝(MTT)比色法检测细胞存活;结晶紫染色法检测细胞毒作用;原位末端标记法(TUNEL)检测凋亡.结果 感染ZD-hTERT、ZD-EGFP的Bel-7402细胞表达ElA;抑制hTERT表达作用依次为ZD-hTERT>Ad-hTERT>ZD-EGFP>Ad-EGFP;抑制Bel-7402细胞生长及细胞毒作用依次为ZD-hTERT>ZD-EGFP=Ad-hTERT>Ad-EGFP.感染ZD-hTERT、ZD-EGFP、Ad-hTERT、Ad-EGFP的Bel-7402细胞凋亡率(%)分别为(88.1±2.2)、(39.2±2.1)、(42.1±5.1)、(7.5±2.1),ZD-hTERT诱导凋亡作用最高(P<0.01).结论 表达hTERT-siRNA的增殖腺病毒能显著抑制人肝癌Bel-7402细胞hTERT基因表达,进而抑制其增殖,促进其凋亡.     

异丙酚对急性肺栓塞大鼠肺细胞凋亡的影响

目的 评价异丙酚对急性肺栓塞大鼠肺细胞凋亡的影响.方法 健康雄性SD大鼠40只,体重280～300 g,随机分为5组(n=8):假手术组(S组)、急性肺栓塞组(APTE组)、异丙酚4 mg·kg-1 ·h-1 组(P1组)、异丙酚8 mg·kg-1 ·h- 1组(P2组)和异丙酚16 mg·kg-1 ·h-1 组(P3组).取尾静脉血样0.2 ml,37℃水浴箱内过夜,分割成直径1 mm ,长5 mm的栓子,颈静脉注射混有15个栓子的2 ml生理盐水制备大鼠肺栓塞模型.S组静脉输注生理盐水2 ml/h 4 h;APTE组、P1组、P2组和P3组制备肺栓塞模型,然后APTE组静脉输注5%葡萄糖2 ml/h4 h,P1 组、P2组和P3组分别静脉输注异丙酚4、8、16 mg·kg-1 ·h-1 (用5%葡萄糖稀释至2 m1)4 h.给药结束后,处死大鼠,取肺组织,采用流式细胞仪检测细胞凋亡情况,计算细胞凋亡率,采用RT-PCR法检测caspase-3、Bcl-2、Box、Fas和FasL的mRNA表达水平,采用Western blot法检测caspase-3、Bcl-2、Bax、Fas和FasL的蛋白表达水平,计算Bcl-2/Bax的mRNA和蛋白表达比值.结果 与S组比较,AVIE组、P1组、P2组和P3 组肺组织细胞凋亡率升高,caspase-3、Bax、Fas、FasL的mRNA和蛋白表达上调,Bcl-2的mRNA和蛋白表达下调,Bcl-2/Bax的mRNA和蛋白表达比值降低(P＜0.05或0.01);与APTE组比较,P1组、P2组和P3 组肺组织细胞凋亡率降低,caspase-3、Bax、Fas、FasL的mRNA和蛋白表达下调,Bcl-2的mRNA和蛋白表达上调,Bcl-2/Bax的mRNA和蛋白表达比值升高(P＜0.05或0.01);P.组、P2组和P3组间肺组织细胞凋亡率、caspase-3、Bcl-2、Bax、Fas、 FasL的mRNA和蛋白表达、Bcl-2/Bax的mRNA和蛋白表达比值差异无统计学意义(P＞0.05).结论 异丙酚可抑制急性肺栓塞大鼠肺细胞凋亡,其机制与下调肺组织caspase-3、Fas和FasL的表达,调节Bcl-2/Bax的平衡有关.     

小剂量阿司匹林协同干扰素-α诱导肝癌BEL-7402细胞凋亡的实验研究

目的 探讨小剂量阿司匹林协同干扰素-α(IFN-α)诱导肝癌BEL-7402细胞凋亡的作用及机制.方法 体外培养的人肝癌BEL-7402细胞经IFN-α单独或联合小剂量阿司匹林处理后,采用MTT法测定细胞的增殖情况;流式细胞术分析不同组药物对BEL-7402细胞凋亡的影响,Western blot检测BEL-7402细胞凋亡相关蛋白表达的变化.结果 MTT法检测显示,与对照组相比,作用48 h时IFN-α组和阿司匹林组的肝癌细胞增殖率分别为82.45％±1.71％和83.22％±2.26％,联合用药组为69.84％±1.18％,联合用药组细胞增殖抑制率明显低于单独用药组(P＜0.05);流式细胞术检测结果显示,IFN-α组和阿司匹林组细胞凋亡率分别为14.78％±1.93％和14.00％±0.61％,联合用药组为21.68％±1.28％,明显高于单独用药组(P＜0.05).Western blot检测发现IFN-α及小剂量阿司匹林可促进caspase-3及caspase-9的表达,而二者联合应用时caspase-3及caspase-9亦被明显激活.进一步检测显示,IFN-α单独或联合阿司匹林可促进肝癌细胞促凋亡蛋白Bax的表达(P＜0.05),而抗凋亡蛋白Bcl-2和Bcl-xl表达未见明显变化(P＞0.05).结论 小剂量阿司匹林可协同IFN-α抑制BEL-7402细胞的增殖,通过激活caspase-3及caspase-9诱导肿瘤细胞凋亡,该作用可能与促凋亡蛋白Bax表达的增高有关.     

HIF-1α通过MMP-2/9途径介导缺氧环境下肝癌细胞侵袭的实验研究

目的:探讨缺氧环境下缺氧诱导因子-1α(HIF-1α)对肝癌细胞侵袭的影响及机制。方法:选取肝癌SMMC-7721/Bel-7402细胞,Western blot检测HIF-1α蛋白在缺氧环境下的表达;将肝癌SMMC-7721细胞分为常氧组、缺氧组、缺氧+con sh RNA组、缺氧+HIF-1αsh RNA组,将慢病毒介导的HIF-1αsh RNA转染细胞,继续培养36 h,Transwell侵袭实验检测细胞侵袭能力,Western blot检测HIF-1α、MMP-1、MMP-2、MMP-9表达。结果:缺氧增强了肝癌细胞HIF-1α表达(缺氧组vs常氧组,均P0.01);缺氧条件下,侵袭细胞数目明显增多(缺氧组vs常氧组:218.33±5.51 vs 105.66±7.02,P0.01);HIF-1α降低后,细胞侵袭能力显著降低(缺氧+Con sh RNA组vs缺氧+HIF-1αsh RNA组:217.33±4.51 vs 127.66±3.06,P0.01);缺氧条件下,HIF-1α上调了MMP-2、MMP-9表达。结论:HIF-1α通过调控MMP-2/9表达增强了缺氧条件下肝癌细胞的侵袭能力。     

西罗莫司诱导人肝癌细胞株BEL-7402凋亡及其机制

目的探讨西罗莫司（SRL）在体外诱导人肝癌细胞株BEL-7402的凋亡作用及其机制。方法以不同浓度的SRL（5、10、20、30、40和50nmol／L）作用于体外培养的人肝癌细胞株BEL-7402，应用流式细胞仪检测培养24、48和72h时的细胞凋亡情况；Hoechst 33258荧光染色法观察细胞凋亡时的形态学变化；Western Blot法观察BEL-7402细胞中Caspase-3、Bcl-2、Bcl-xl和Bax基因的表达变化；采用Caspase-3试剂盒检测Caspase-3酶的活性；JCl染色法检测细胞线粒体膜电位（△ψbm）。结果SRL可诱导BEL-7402细胞凋亡，并与药物浓度和作用时间呈正相关。SRL作用BEL-7402细胞后48h，在Hoechst33258荧光染色图片上可见核浓缩及核碎裂等典型的细胞凋亡特征，凋亡过程中线粒体膜电位下降及Caspase-3酶原蛋白激活，伴有Bcl-2、Bcl-xl蛋白表达的降低和Bax蛋白上调。结论SRL能使抗凋亡蛋白Bcl-2、gcl-xl表达降低，促凋亡蛋白Bax表达上调，线粒体膜电位下降，激活Caspase-3酶原蛋白，从而诱导细胞凋亡。     

金属硫蛋白对供心细胞凋亡的影响

目的探讨金属硫蛋白(MT)对供心细胞凋亡和凋亡蛋白表达的影响.方法 Wistar大鼠16只,按腹腔注射的药物不同分为2组,每组各8只.对照组:腹腔注射蒸馏水0.5ml,24小时后取离体心脏,灌注HTK心脏停搏液,4℃保存3小时后建立Langendorff灌注模型,灌注重碳酸盐缓冲液(KH)2小时;实验组:腹腔注射3.6% ZnSO4(1.5ml/kg),其余处理同对照组.测定心肌MT含量、心肌细胞凋亡率、琼脂糖凝胶电泳检测DNA片段梯、B淋巴细胞瘤/白血病2蛋白(Bcl-2)、Bcl-2家族Bax蛋白和Fas蛋白的表达.结果实验组与对照组比较,MT含量明显增高(P＜0.01),心肌细胞凋亡率明显降低(P<0.01),琼脂糖凝胶电泳检测DNA片段梯光密度明显减弱(P<0.01),Bcl-2表达明显增高,Bax和Fas表达明显减弱(P＜0.01).结论心肌MT可通过调节Bcl-2、Bax和Fas蛋白的表达降低供心心肌细胞凋亡率.     

BDNF|TrkB在原发性肝癌中的表达及BDNF对肝癌细胞株Bel-7402的作用

目的探讨脑源性神经营养因子(BDNF)及其受体TrkB在原发性肝癌中的表达及BDNF对肝癌细胞株Bel-7402的作用。方法 (1)检测肝癌组织、癌旁组织及正常肝组织中BDNF和TrkB的表达,分析BDNF和TrkB的表达与临床病理因素之间的关系。(2)检测BDNF,TrkB,Bcl-2在肝癌细胞株Bel-7402及正常肝细胞株L-02的表达及其对Bel-7402细胞增殖、失巢凋亡、黏附、浸润转移能力的影响。结果 (1)肝癌组织中BDNF呈高表达(60.4%,29/48),与Edmondson分级、有无包膜有关(P0.05);TrkB表达率为52.1%(25/48),与Edmondson分级及肿瘤结节数有关(P0.05);BDNF与TrkB在肝癌中的表达呈正相关(r=0.332,P0.05)。BDNF和TrkB在正常肝组织中均无表达。两者在肝癌组织中表达远高于癌旁组织中的表达(P0.01)。肝癌组织中BDNF和TrkB呈高表达者,其2年内复发率增高(P0.05)及生存率下降(P0.01)。(2)外源性BDNF均能增强Bel-7402细胞的增殖、黏附、体外迁移、侵袭能力及抵抗失巢凋亡的能力(P0.01);(3)各浓度的BDNF均可上调Bel-7402细胞Bcl-2 mRNA及其蛋白的表达(P0.05)。结论 (1)BDNF及TrkB在肝癌中高表达,可能与复发、生存率有关;(2)BDNF可调节肝癌细胞的生长、黏附、迁移和侵袭;(3)BDNF可上调Bcl-2的表达,抑制肿瘤细胞的失巢凋亡。     

Involved intrinsic apoptotic pathway of testicular tissues in varicocele-induced rats

Introduction  Increased testicular germ cell apoptosis has been reported in varicocele-induced rats. We studied intrinsic or extrinsic pathway of apoptosis by detecting Bcl-2, caspase-9, caspase-8, and activated caspase-3 expressions in the bilateral testes of experimental varicocele-induced rats. Materials and methods  Experimental left varicocele (ELV) was created by partial ligation of left renal vein in a study group of 24 adult male Sprague–Dawley rats. The other 24 rats were as control group. Eight rats from each group were killed at 4, 8, and 12 weeks following varicocele creation. Testicular tissues of both groups were sampled for TUNEL assay and immunoblotting. Results  Increased apoptotic germ cell was found in the ipsilateral testis of varicocele group at 8 and 12 weeks after operation (P < 0.05). Increased activated caspase-3 expression in the contralateral (right) testis was noted at 12 weeks following varicocele creation (P < 0.05). Conclusions  Our study demonstrates down-regulation of Bcl-2 expression and increased expressions of caspase-9 and activated caspase-3 in the ipsilateral testis of ELV rats at 8 and 12 weeks, indicating gradually increased testicular tissues apoptosis through the intrinsic pathway in varicocele-induced rats. Simultaneously, increased apoptosis in the contralateral testis was observed at 12 weeks (P < 0.05) following varicocele creation also.     

Serenoa repens extract targets mitochondria and activates the intrinsic apoptotic pathway in human prostate cancer cells

OBJECTIVE

To investigate the effects of Serenoa repens extract (Sr) in human PC3 and LNCaP prostate cancer and MCF7 breast cancer cells, with specific emphasis on the role of the mitochondrial apoptotic pathway, as the molecular pathway through which Sr, a natural product of plant origin, induces death of prostate cancer cells in culture is still unknown.

MATERIAL AND METHODS

Cellular and mitochondrial structure and function, and the cell cycle, were analysed using light, electron and fluorescence microscopy, spectrophotometry and flow cytometry. Apoptosis was evaluated using biochemical and cytohistochemical methods.

RESULTS

Cells treated with Sr underwent massive vacuolization and cytosolic condensation, followed by cell death only in the prostate lines. Within minutes of adding Sr to prostate cells, it caused opening of the permeability transition pore (PTP), which led to complete mitochondrial depolarization within 2 h, and to the appearance of small, pycnotic mitochondria. Release of cytochrome c and SMAC/Diablo to the cytosol was detectable after 4 h of treatment, while caspase 9 activation and poly(ADP‐ribose) polymerase 1 cleavage occurred at 16 h, followed by appearance of a sub‐G1 peak and apoptosis at 24 h.

CONCLUSION

Sr selectively induces apoptotic cell death of prostate cancer cells through the intrinsic pathway, and activation of the mitochondrial PTP might play a central role in this process.     

Activation of a Ca2+-Mg2+-dependent endonuclease as an early event in castration-induced prostatic cell death

Previous studies have demonstrated that castration-induced androgen withdrawal results in the fragmentation of prostatic DNA into nucleosomal oligomers, and this process comprises an early event in the activation of programed cell death in the rat ventral prostate. This DNA fragmentation could be due to changes in the chromatin conformation increasing its sensitivity to preexisting nucleases and/or to increases in the activity of the nucleases themselves. However, comparative kinetic analysis of in vitro DNA fragmentation induced by exogenous nucleases did not reveal any differences in the sensitivity of prostatic chromatin between intact and castrated rats. In contrast to these negative findings, using [3H] DNA as an exogenous substrate, it was shown that within the first day following castration there was a twofold increase in a Ca2+-Mg2+-dependent nuclease activity without a concomitant increase in other nuclear nucleases. This Ca2+-Mg2+-dependent nuclease activation occurred coincidental with the initial increase in nuclear DNA fragmentation following castration and preceded the enhanced appearance of morphological changes characteristic of dying cells (i.e., apoptosis), as well as the major increase in prostatic DNA loss. These results suggest that castration-induced androgen deprivation leads to a sequential activation of a Ca2+-Mg2+-dependent nuclease leading to the fragmentation of the genome into discrete nucleosomal-sized fragments of DNA, subsequently followed by the fragmentation of the nucleus itself (i.e., apoptosis) and eventually with the complete digestion of the nucleosomal oligomers into component nucleotides (i.e., DNA loss). Since the castration-induced nuclease is dependent upon calcium ions for maximal activity, a potential role of intracellular calcium in the early events activating prostatic cell death was investigated. Acute disturbances in intracellular calcium homeostasis within the ventral prostate by means of a potent calcium influx blocker, nifedipine, simultaneous with castration, resulted in a significant delay in the biochemical and morphological changes associated with prostatic cell death (i.e., prostatic weight loss, prostatic DNA loss, and DNA fragmentation). These results point to a potential role of intracellular calcium levels in the mechanism of activation of castration-induced death of the androgen-dependent epithelial cells in the ventral prostate.     

CBA/N、nude和SCID小鼠肝癌模型的建立及凋亡相关基因的表达

目的 研究CBA/N，nude和SCID小鼠人肝癌模型制作，凋亡相关基因的表达和意义。方法 将人肝癌细胞系HHCC-9724-P种于动物不同部位，观察肿瘤的生长特点，免疫组织化学SP法研究肝内肿瘤组织中的Bcl-2,Bax,VEGF和P53的表达。结果 除CBA/N小鼠皮下接种无法成活外其它小鼠在各部位均可成活，在同时间的肿瘤组织体积和重量SCID小鼠最大，3种小鼠肝内肿瘤组织从第一周开始4种基因的表达明显增强，三周时阳性细胞率达最高水平，而Bcl-2和VEGF的阳性细胞率高于Bax和P53。结论 由于较高的肿瘤成活率和凋亡相关基因表达的敏感性，SCID小鼠在人肝癌模制作中是较好的实验动物。     

Intravenous Infusion of Apoptotic Cells Simultaneously with Allogeneic Hematopoietic Grafts Alters Anti-Donor Humoral Immune Responses

Intravenous infusion of apoptotic donor or third-party leukocytes simultaneously with an allogeneic donor bone marrow (BM) graft favors engraftment across major histocompatibility barriers. While verifying that such apoptotic cell infusion might not also be associated with antibody (Ab)-mediated allo-immune responses, we found, rather strikingly, that apoptotic cell infusion could in fact successfully prevent a humoral allo-immunization against a BM graft in mice. Indeed, among recipients having rejected their BM graft, prior apoptotic cell infusion was associated with a near absence of Ab-mediated allo-responses, while such an immunization was frequently observed in the absence of apoptotic cell infusion. This was also observed when infusing host apoptotic cells, thus showing that the prevention of immunization was linked to the apoptotic state of the cells rather than mediated by residual anti-recipient activity. In vivo anti-transforming growth factor-beta (TGF-beta) treatment resulted in the loss of this apoptotic cell infusion-associated protective effect on humoral allo-responses. Further studies will determine whether apoptotic cell infusion, in addition to hematopoietic graft facilitation might also contribute to preventing deleterious Ab-mediated allo-responses in various transplantation settings.     

The role of clinical care pathways: an experience with distal pancreatectomy

Background

Previous studies have indicated that clinical pathways may shorten hospital length of stay (HLOS) among patients undergoing distal pancreatectomy (DP). Here, we evaluate an institutional standardized care pathway (SCP) for patients undergoing DP.

Materials and methods

A retrospective review of patients undergoing DP from November 2006 to November 2012 was completed. Patients treated before and after implementation of the SCP were compared. Multivariable linear regression was then performed to identify independent predictors of HLOS.

Results

There were no differences in patient characteristics between SCP (n = 50) and pre-SCP patients (n = 100). Laparoscopic technique (62% versus 13%, P < 0.001), splenectomy (52% versus 38%, P = 0.117), and concomitant major organ resection (24% versus 13%, P = 0.106) were more common among SCP patients. Overall, important complication rates were similar (24% versus 26%, P = 0.842). SCP patients resumed a normal diet earlier (4 versus 5 d, P = 0.025) and had shorter HLOS (6 versus 7 d, P = 0.026). There was no increase in 30-d resurgery or readmission. In univariate comparison, SCP, cancer diagnoses, intraductal papillary mucinous neoplasm diagnoses, neoadjuvant therapy, operative technique, major organ resection, and feeding tube placement were associated with HLOS; however, after multivariable adjustment, only laparoscopic technique (−33%, P = 0.001), concomitant major organ resection (+38%, P < 0.001), and feeding tube placement (+68%, P < 0.001) were independent predictors of HLOS.

Conclusions

Implementation of a clinical pathway did not improve HLOS at our institution. The increasing use of laparoscopy likely accounts for shorter HLOS in the SCP cohort. In the future, it will be important to identify clinical scenarios most likely to benefit from implementation of a clinical pathway.     

线粒体途径相关信号通路对成骨细胞凋亡的作用

骨质疏松症是由于多种原因导致的骨质量和骨密度下降,骨微结构遭到破坏,造成骨脆性增加,从而容易发生骨折的一种全身性代谢性骨病变。其中,成骨细胞是促进骨形成的主要功能细胞,是骨质疏松发生的关键细胞,其功能退变和异常凋亡将会引起骨量丢失,诱导骨质疏松发生。因此,探究成骨细胞的凋亡机制对预防和治疗骨质疏松症具有重要意义。其中,线粒体途径是成骨细胞凋亡的主要途径,是由多基因参与、多通路相互作用而形成的复杂过程。因此,本文综述了线粒体途径的凋亡过程及其众多相关信号通路:PI3k/Akt信号通路、MAPK信号通路、Ca~(2+)/CaM信号通路以及其他信号通路和因子(Keap1/Nrf2信号通路、PHB、FoxO家族、cAMP/CREB),同时还归纳了这些信号通路在成骨细胞经线粒体途径凋亡的过程中发挥的促进或者抑制作用,以及他们在成骨细胞凋亡中的一些相互作用。这为进一步探究成骨细胞的凋亡机制和骨质疏松的发病机制提供了可靠依据,也为更深入研究安全、有效的抗骨质疏松药物提供了一些可能的作用靶点(如:Akt、ERK、JNK、p38、Ca~(2+)、PHB、FoxO3a、CREB、Keap1/Nrf2等)。