NF-κB抑制剂对脑出血大鼠神经损伤的影响

发布时间：2018-02-09 08:06

本文关键词： 核因子κB抑制剂细胞凋亡脑出血氧化应激　出处：《中国病理生理杂志》2017年12期 　论文类型：期刊论文

【摘要】：目的:探讨核因子κB(NF-κB)抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)对脑出血(ICH)大鼠神经功能及神经细胞凋亡的调节作用。方法:取SPF级SD大鼠随机分假手术组(sham组)、ICH组、PDTC低浓度组(Plow组)和PDTC高浓度组(P_(high)组),每组6只。采用自体血注入法建立大鼠ICH模型,Plow组和P_(high)组在缺血后2h分别给予100 mg/kg和200 mg/kg的PDTC腹腔注射,sham组和ICH组给予等体积的生理盐水;24 h后,采用改良的Longa分级法进行神经功能评分;TUNEL法测定神经细胞凋亡情况;并检测脑组织中丙二醛(MDA)的含量和超氧化物歧化酶(SOD)的活性。此外,采用Western blot法检测脑组织中p-P65及cleaved caspase-3的蛋白水平。结果:与sham组相比,ICH组大鼠的神经功能评分显著升高(P0.05);应用PDTC后,Plow组和P_(high)组动物的神经功能评分都有所降低,但2组间差异无统计学意义。与sham组相比,ICH组大鼠神经细胞凋亡明显增多(P0.05);应用PDTC后,2组动物神经细胞凋亡数目显著降低,且P_(high)组的细胞凋亡数目显著低于Plow组(P0.05)。与sham组相比,ICH组大鼠脑组织的MDA含量升高,SOD活性降低(P0.05);应用PDTC后,2组动物脑组织中的MDA含量显著降低,而SOD活性升高,且这一趋势在P_(high)组表现更为明显。与sham组相比,ICH组大鼠脑组织中p-P65和cleaved caspase-3的蛋白水平显著增加(P0.05);应用PDTC后,2组动物脑组织中p-P65和cleaved caspase-3的蛋白水平显著降低,且P_(high)组中p-P65和cleaved caspase-3的蛋白水平显著低于Plow组。结论:NF-κB抑制剂PDTC能减轻脑出血后继发性脑损伤,且大剂量作用效果较好;其作用机制可能与降低MDA含量、提高SOD活性进而抑制神经细胞凋亡有关。
[Abstract]:Objective: to investigate the effects of pyrrolidine dithiocarbamate (PDT), a inhibitor of nuclear factor 魏 B (NF- 魏 B) NF- 魏 B, on nerve function and neuronal apoptosis in rats with intracerebral hemorrhage. Methods: SD rats of grade SPF were randomly divided into sham group and sham group. The ICH model of rats was established by autologous blood injection. The rats in the two groups were given 100 mg/kg and 200 mg/kg PDTC intraperitoneal injection of #number0# mg/kg and 200 mg/kg, respectively, and the ICH group were given the same volume at 2 hours after ischemia. After 24 hours of normal saline, The neuronal apoptosis was determined by modified Longa grading and Tunel method, and the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in brain tissue were detected. The protein levels of p-P65 and cleaved caspase-3 in brain tissue were detected by Western blot method. Results: compared with sham group, the neurological function scores of rats in ICH group were significantly increased (P 0.05), and those in low group and high group were decreased after PDTC. However, there was no significant difference between the two groups. Compared with the sham group, the apoptosis of nerve cells in the ICH group was significantly increased (P 0.05), and the number of neuronal apoptosis in the PDTC group was significantly lower than that in the control group. Compared with the sham group, the MDA content in the brain tissue increased and the activity of sod decreased. After the application of PDTC, the content of MDA in the brain tissue of the two groups decreased significantly, but the activity of SOD increased. Compared with the sham group, the protein levels of p-P65 and cleaved caspase-3 in the brain tissue of the sham group were significantly increased, and the protein levels of p-P65 and cleaved caspase-3 in the brain tissue of the two groups were significantly decreased after the application of PDTC. The protein levels of p-P65 and cleaved caspase-3 were significantly lower than those in Plow group. Conclusion PDTC can reduce the secondary brain injury after intracerebral hemorrhage, and the effect of high dose treatment is better, and the mechanism may be related to the decrease of MDA content. It is related to the increase of SOD activity and the inhibition of neuronal apoptosis.
【作者单位】：台州市中心医院神经外科;
【分类号】：R743.34

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