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Paeoniflorin inhibits nucleus pulposus cell apoptosis by regulating the expression of Bcl-2 family proteins and caspase-9 in a rabbit model of intervertebral disc degeneration

机译:eon药苷通过调节兔椎间盘退变模型中Bcl-2家族蛋白和caspase-9的表达来抑制髓核细胞凋亡

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Apoptosis plays a key role in the pathogenesis of internal disc disruption (IDD); therefore, the inhibition of apoptosis may offer a novel approach for treating IDD diseases. The aim of the present study was to investigate the effects and the underlying mechanisms of paeoniflorin through the detection of relevant indicators in a rabbit model of IDD. In total, 144 rabbits were used in the study and divided into four groups (n=36 per group). Rabbits successfully modeled with IDD received an intragastric injection of 120 mg/kgday paeoniflorin (high-dose group), 30 mg/kgday paeoniflorin (low-dose group) or saline (model saline group), while rabbits without IDD were used as a normal control group. The apoptosis rate of disc nucleus pulposus cells was detected using flow cytometry. In addition, the expression levels of Bcl-2, Bax and caspase-9 in the disc tissues were detected using immunohistochemistry and western blot analysis prior to and following the treatment. The results indicated that the expression levels of Bax in the low- and high-dose paeoniflorin groups were significantly reduced, while the Bcl-2 expression levels were significantly increased when compared with the model saline group (P<0.01). In addition, the expression levels of cleaved caspase-3 and cleaved caspase-9 were reduced in the low- and high-dose paeoniflorin groups, as compared with the model saline group (P<0.05). Furthermore, the average apoptotic index of the high- and low-dose paeoniflorin groups was decreased when compared with the model saline group (P<0.05). In conclusion, paeoniflorin was demonstrated to inhibit the apoptosis of nucleus pulposus cells and the activation of caspase-3 and caspase-9 through the regulation of Bcl-2 family protein expression. These results provide an experimental basis for the future treatment of IDD with paeoniflorin.
机译:凋亡在内部椎间盘破裂(IDD)的发病机理中起着关键作用。因此,抑制细胞凋亡可能为治疗IDD疾病提供一种新方法。本研究的目的是通过检测IDD兔模型中的相关指标来研究pa药苷的作用及其潜在机制。该研究总共使用了144只兔子,分为四组(每组n = 36)。成功使用IDD建模的兔子接受了120 mg / kgday eon药苷(高剂量组),30 mg / kgday eon药苷(低剂量组)或生理盐水(模型盐水组)的胃内注射,而未使用IDD的兔则作为正常控制组。流式细胞仪检测椎间盘髓核细胞的凋亡率。另外,在治疗之前和之后,使用免疫组织化学和蛋白质印迹分析检测椎间盘组织中Bcl-2,Bax和caspase-9的表达水平。结果表明,与模型盐水组相比,低剂量和大剂量pa药苷组中Bax的表达水平显着降低,而Bcl-2表达水平显着升高(P <0.01)。此外,与模型盐水组相比,低剂量和高剂量pa药苷组中裂解的caspase-3和裂解的caspase-9的表达水平降低(P <0.05)。此外,与模型盐水组相比,高剂量和低剂量pa药苷组的平均凋亡指数降低(P <0.05)。总之,pa药苷被证明通过调节Bcl-2家族蛋白的表达来抑制髓核细胞的凋亡以及caspase-3和caspase-9的活化。这些结果为将来用flor药苷治疗IDD提供了实验依据。

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