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Separate administration of ammonium pyrrolidinedithiocarbamate and phorbol myristate acetate at early and late stages decreases secondary brain injury following intracerebral haemorrhage in rats via the NF-κB pathway.
Folia Neuropathologica ( IF 1.5 ) Pub Date : 2020-06-30 , DOI: 10.5114/fn.2020.96801 Yan Song 1 , Qibing Huang 1 , Zeli Zhang 1 , Feng Li 2 , Zhenkuan Xu 3
Folia Neuropathologica ( IF 1.5 ) Pub Date : 2020-06-30 , DOI: 10.5114/fn.2020.96801 Yan Song 1 , Qibing Huang 1 , Zeli Zhang 1 , Feng Li 2 , Zhenkuan Xu 3
Affiliation
Introduction
Nuclear factor-kB (NF-kB) is a critical regulator of inflammatory responses following intracerebral haemorrhage (ICH). According to our previous study, inhibiting the p65 subunit at an early stage after ICH can reduce cell death, while inhibiting c-Rel at a late stage can lead to the opposite result. The aim of this study is to clarify whether patient prognosis can be improved by inhibiting p65 at the early stage and promoting c-Rel at the late stage.
Material and methods
Rats were divided into a sham group, ICH group, early NF-kB-inhibiting group using ammonium pyrrolidinedithiocarbamate (PDTC; group A, p65 subunit was dominant and inhibited at the early stage), late NF-kB-activating group using phorbol myristate acetate (PMA; group B, c-Rel was dominant and promoted at the late stage), and early NF-kB-inhibiting and late-activating group (group C, p65 subunit was inhibited at the early stage and c-Rel was promoted at the late stage). At preset time points after ICH, perihematomal tissue was obtained for detection of NF-kB activation, cell death, and expression of caspase-3, Bcl-2, and NF-kB subunits, to evaluate of the effect of PDTC and PMA.
Results
At four days after ICH, p65 expression (p < 0.01) and the number of TUNEL-positive cells (p < 0.01) in group AÂ were significantly lower than in the ICH group. At 10 days after ICH, c-Rel expression in groups B and C was significantly higher than in other groups (p < 0.01 for all). TUNEL-positive cell numbers in groups AÂ and B were significantly lower than in the ICH group, though more numerous than in group C (p < 0.01 for all).
Conclusions
Administration of both PDTC at the early stage and PMA at the late stage reduced perihematomal cell death after ICH, and using the two reagents together had a stronger anti-apoptotic effect than separate usage.
中文翻译：
在早期和晚期分别给予吡咯烷二硫代氨基甲酸铵和肉豆蔻酸乙酸佛波酯可减少大鼠脑内出血后通过NF-κB途径继发的脑损伤。
简介
核因子-kB（NF-kB）是脑出血（ICH）后炎症反应的关键调节剂。根据我们之前的研究，在ICH后早期抑制p65亚基可以减少细胞死亡，而在晚期抑制c-Rel可以导致相反的结果。这项研究的目的是阐明是否可以通过在早期抑制p65并在晚期抑制c-Rel来改善患者的预后。
材料与方法
将大鼠分为假手术组，ICH组，使用吡咯烷二硫代氨基甲酸铵的早期NF-kB抑制组（PDTC； A组，p65亚基占主导并在早期被抑制），晚期使用肉豆蔻酸佛波酯的NF-kB激活组（PMA； B组，c-Rel在晚期占优势并被促进），早期NF-kB抑制和后期激活组（C组，p65亚基在早期被抑制，c-Rel在早期被抑制。后期）。在ICH后的预设时间点，获取血肿周围组织以检测NF-kB活化，细胞死亡以及caspase-3，Bcl-2和NF-kB亚基的表达，以评估PDTC和PMA的作用。
结果
ICH后四天，A组的p65表达（p <0.01）和TUNEL阳性细胞数（p <0.01）明显低于ICH组。ICH后第10天，B组和C组的c-Rel表达明显高于其他组（所有P均<0.01）。A组和B组的TUNEL阳性细胞数显着低于ICH组，尽管比C组要多（所有p <0.01）。
结论
早期给予PDTC和晚期给予PMA均可减少ICH后血肿周围细胞的死亡，并且与单独使用相比，两种试剂一起使用具有更强的抗凋亡作用。
更新日期：2020-08-20
Nuclear factor-kB (NF-kB) is a critical regulator of inflammatory responses following intracerebral haemorrhage (ICH). According to our previous study, inhibiting the p65 subunit at an early stage after ICH can reduce cell death, while inhibiting c-Rel at a late stage can lead to the opposite result. The aim of this study is to clarify whether patient prognosis can be improved by inhibiting p65 at the early stage and promoting c-Rel at the late stage.
Material and methods
Rats were divided into a sham group, ICH group, early NF-kB-inhibiting group using ammonium pyrrolidinedithiocarbamate (PDTC; group A, p65 subunit was dominant and inhibited at the early stage), late NF-kB-activating group using phorbol myristate acetate (PMA; group B, c-Rel was dominant and promoted at the late stage), and early NF-kB-inhibiting and late-activating group (group C, p65 subunit was inhibited at the early stage and c-Rel was promoted at the late stage). At preset time points after ICH, perihematomal tissue was obtained for detection of NF-kB activation, cell death, and expression of caspase-3, Bcl-2, and NF-kB subunits, to evaluate of the effect of PDTC and PMA.
Results
At four days after ICH, p65 expression (p < 0.01) and the number of TUNEL-positive cells (p < 0.01) in group AÂ were significantly lower than in the ICH group. At 10 days after ICH, c-Rel expression in groups B and C was significantly higher than in other groups (p < 0.01 for all). TUNEL-positive cell numbers in groups AÂ and B were significantly lower than in the ICH group, though more numerous than in group C (p < 0.01 for all).
Conclusions
Administration of both PDTC at the early stage and PMA at the late stage reduced perihematomal cell death after ICH, and using the two reagents together had a stronger anti-apoptotic effect than separate usage.
中文翻译：
在早期和晚期分别给予吡咯烷二硫代氨基甲酸铵和肉豆蔻酸乙酸佛波酯可减少大鼠脑内出血后通过NF-κB途径继发的脑损伤。
简介
核因子-kB（NF-kB）是脑出血（ICH）后炎症反应的关键调节剂。根据我们之前的研究，在ICH后早期抑制p65亚基可以减少细胞死亡，而在晚期抑制c-Rel可以导致相反的结果。这项研究的目的是阐明是否可以通过在早期抑制p65并在晚期抑制c-Rel来改善患者的预后。
材料与方法
将大鼠分为假手术组，ICH组，使用吡咯烷二硫代氨基甲酸铵的早期NF-kB抑制组（PDTC； A组，p65亚基占主导并在早期被抑制），晚期使用肉豆蔻酸佛波酯的NF-kB激活组（PMA； B组，c-Rel在晚期占优势并被促进），早期NF-kB抑制和后期激活组（C组，p65亚基在早期被抑制，c-Rel在早期被抑制。后期）。在ICH后的预设时间点，获取血肿周围组织以检测NF-kB活化，细胞死亡以及caspase-3，Bcl-2和NF-kB亚基的表达，以评估PDTC和PMA的作用。
结果
ICH后四天，A组的p65表达（p <0.01）和TUNEL阳性细胞数（p <0.01）明显低于ICH组。ICH后第10天，B组和C组的c-Rel表达明显高于其他组（所有P均<0.01）。A组和B组的TUNEL阳性细胞数显着低于ICH组，尽管比C组要多（所有p <0.01）。
结论
早期给予PDTC和晚期给予PMA均可减少ICH后血肿周围细胞的死亡，并且与单独使用相比，两种试剂一起使用具有更强的抗凋亡作用。
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