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首页> 外文期刊>Apoptosis >Lentiviral shRNA silencing of CHOP inhibits apoptosis induced by cyclic stretch in rat annular cells and attenuates disc degeneration in the rats
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Lentiviral shRNA silencing of CHOP inhibits apoptosis induced by cyclic stretch in rat annular cells and attenuates disc degeneration in the rats

机译：CHOP的慢病毒shRNA沉默抑制大鼠环状细胞循环拉伸诱导的凋亡并减轻大鼠椎间盘退变

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摘要

The expression of CHOP (C/EBP homologous protein), an apoptosis regulated gene, increases during endoplasmic reticulum (ER) stress induced by cyclic stretch and leads to rat AF cells apoptosis. However, whether the suppression of CHOP can inhibit apoptosis and attenuates disc degeneration by cyclic stretch remains unclear. The aim of this study was to evaluate the suppressive effects of lentiviral CHOP shRNA on apoptosis induced by cyclic stretch in rat annulus fibrosus (AF) cells in vitro and disc degeneration of rat lumber spine in vivo. Lentiviral CHOP shRNA was constructed and introduced into AF cells. After stretched by the Flexcell Tension Plus system with 20% elongation for 36 h, silencing of the CHOP gene was identified by RT-PCR and Western blot. Inhibition of apoptosis was detected by flow cytometry, and nuclei morphologic changes were visualized by Hoechst 33258 staining. The effect of CHOP shRNA on disc degeneration was determined in vivo by using a rat model. At 7 weeks after intradiscal injection of the control or CHOP shRNA in the L4/L5 and L5/L6 discs, disc degeneration was assessed by X-ray examination, magnetic resonance imaging (MRI) assessment, and HE and TUNEL staining. A significant decrease in CHOP mRNA and protein expression was detected in AF cells with CHOP shRNA transfection after 36 h stretch. There was a significant decrease in apoptotic incidence in cells treated with CHOP shRNA, which was parallel to the expression of CHOP. Injection of CHOP shRNA in vivo resulted in the improvement in MRI and histologic score, and decrease in the apoptosis in the disc. No significant change in disc height was observed. In conclusion, a novel lentiviral vector expressing CHOP shRNA efficiently inhibits apoptosis in rat AF cells by silencing CHOP expression. In a rat model, intradiscal injection of CHOP shRNA induces the suppression of disc degeneration. The therapeutic effects of lentiviral CHOP shRNA should be further explored.
机译：CHOP（C / EBP同源蛋白）（一种凋亡调控基因）的表达在由循环拉伸引起的内质网（ER）应激期间增加，并导致大鼠AF细胞凋亡。但是，尚不清楚CHOP的抑制是否可以抑制细胞凋亡并通过周期性拉伸来减轻椎间盘退变。这项研究的目的是评估慢病毒CHOP shRNA对大鼠环状纤维（AF）细胞的循环拉伸诱导的细胞凋亡的抑制作用以及体内对大鼠腰椎椎间盘退变的抑制作用。构建慢病毒CHOP shRNA，并将其引入AF细胞。通过Flexcell Tension Plus系统以20％的伸长率拉伸36小时后，通过RT-PCR和Western印迹鉴定CHOP基因的沉默。通过流式细胞术检测凋亡的抑制作用，并通过Hoechst 33258染色观察细胞核形态变化。通过使用大鼠模型，在体内确定了CHOP shRNA对椎间盘变性的作用。在椎间盘内向L4 / L5和L5 / L6椎间盘中注射对照或CHOP shRNA后7周，通过X射线检查，磁共振成像（MRI）评估以及HE和TUNEL染色评估椎间盘退变。拉伸36 h后，CHOP shRNA转染的AF细胞中CHOP mRNA和蛋白表达显着降低。用CHOP shRNA处理的细胞凋亡率显着降低，这与CHOP的表达平行。体内注射CHOP shRNA可改善MRI和组织学评分，并减少椎间盘的凋亡。椎间盘高度未观察到明显变化。总之，表达CHOP shRNA的新型慢病毒载体可通过沉默CHOP表达来有效抑制大鼠AF细胞凋亡。在大鼠模型中，椎间盘内注射CHOP shRNA可抑制椎间盘退变。慢病毒CHOP shRNA的治疗作用应进一步探讨。

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