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目的探讨MK-801对梗阻性黄疸大鼠中枢神经抗氧化应激系统的影响。方法 20只大鼠随机均分为假手术组、对照组、MK-801低剂量组和MK-801高剂量组4组,后3组为梗阻性黄疸模型组。MK-801低剂量组和MK-801高剂量于梗阻性黄疸模型建模术后第2天起分别腹腔注射0.025 mg/(kg·d)和0.25 mg/(kg·d)的MK-801,共10 d;假手术组和对照组则以等容量生理盐水同时点注射。4组大鼠于术后3 d采尾部静脉血检查直接胆红素(DBIL)和总胆汁酸(TBA)以确定模型制作是否成功,术后10 d处死大鼠并取大脑皮质按试剂盒要求行丙二醛(MDA)、过氧化氢酶(CAT)、总超氧化物歧化酶(T-SOD)及总抗氧化能力(T-AOC)含量或活性测定。结果1建模术后3 d,对照组、MK-801低剂量组和MK-801高剂量组大鼠的DBIL和TBA水平明显升高,且出现全身皮肤黄染,提示梗阻性黄疸模型建模成功。2对照组、MK-801低剂量组和MK-801高剂量组的MDA含量均明显高于假手术组(P<0.05),MK-801低剂量组和MK-801高剂量组MDA含量则明显低于对照组(P<0.05),MK-801低剂量组和MK-801高剂量组间MDA含量的差异无统计学意义(P>0.05)。3对照组CAT活性低于假手术组(P<0.05),MK-801低剂量组和MK-801高剂量组的CAT活性明显高于假手术组及对照组(P<0.05),MK-801低剂量组和MK-801高剂量组之间CAT活性差异无统计学意义(P>0.05)。4对照组T-SOD活性明显低于假手术组(P<0.05),MK-801低剂量组T-SOD活性则明显高于对照组(P<0.05),MK-801高剂量组T-SOD活性高于对照组但低于MK-801低剂量组(P<0.05)。5对照组、MK-801低剂量组和MK-801高剂量组的T-AOC明显高于假手术组(P<0.05)。MK-801低剂量组和MK-801高剂量组的T-AOC又明显高于对照组(P<0.05),但MK-801低剂量组和MK-801高剂量组间T-AOC的差异无统计学意义(P>0.05)。结论梗阻性黄疸时机体中枢神经系统存在氧化应激反应,机体通过增加CAT等抗氧化应激损伤酶类的表达使抗氧化应激损伤能力增强。MK-801使梗阻性黄疸所致大鼠中枢神经系统氧化应激损伤过程中脂质过氧化程度降低,并可提高SOD及CAT的活性及机体总抗氧化应激能力;高剂量的MK-801与低剂量的MK-801相比其效果并未明显增加,反而使T-SOD活性比低剂量组降低。具体机理需要进一步研究。
Objective To investigate the effect of MK-801 on central nervous system anti-oxidative stress in rats with obstructive jaundice. Methods Twenty rats were randomly divided into 4 groups: sham operation group, control group, MK-801 low dose group and MK-801 high dose group. The latter 3 groups were obstructive jaundice model group. MK-801 low dose group and MK-801 high dose in obstructive jaundice model were intraperitoneal injection of 0.025 mg / (kg · d) and 0.25 mg / (kg · d) of MK-801, A total of 10 d; sham-operated group and control group with equal volume of saline at the same time point injection. The rats in 4 groups were sacrificed 3 days after operation to collect tail vein blood to check the direct bilirubin (DBIL) and total bile acid (TBA) to determine whether the model was successfully established. After 10 days, the rats were sacrificed and the cerebral cortex was taken as required by the kit The contents of malondialdehyde (MDA), catalase (CAT), total superoxide dismutase (T-SOD) and total antioxidant capacity (T-AOC) Results 3 days after modeling, the levels of DBIL and TBA in the control group, MK-801 low-dose group and MK-801 high-dose group were significantly increased, and the yellow skin of the body appeared, suggesting that obstructive jaundice model was modeled success. The content of MDA in the control group, MK-801 low dose group and MK-801 high dose group were significantly higher than those in the sham operation group (P <0.05). The MDA content in MK-801 low dose group and MK-801 high dose group were significantly (P <0.05). There was no significant difference in MDA content between MK-801 low dose group and MK-801 high dose group (P> 0.05). CAT activity in control group was lower than that in sham-operated group (P <0.05). CAT activity in MK-801 low dose group and MK-801 high dose group was significantly higher than that in sham operation group and control group There was no significant difference in CAT activity between the low-dose group and MK-801 high-dose group (P> 0.05). The activity of T-SOD in the control group was significantly lower than that in the sham operation group (P <0.05), while the activity of T-SOD in the low dose MK-801 group was significantly higher than that in the control group (P <0.05) Activity than the control group but lower than MK-801 low-dose group (P <0.05). 5 T-AOC in MK-801 low dose group and MK-801 high dose group were significantly higher than those in sham operation group (P <0.05). The T-AOC of MK-801 low dose group and MK-801 high dose group were significantly higher than that of the control group (P <0.05), but the differences of T-AOC between MK-801 low dose group and MK- Statistical significance (P> 0.05). Conclusion Obstructive jaundice may cause oxidative stress in the central nervous system. The body’s ability of anti-oxidative stress injury is enhanced by increasing the expression of enzymes such as CAT and other antioxidant stress-induced injury. MK-801 can reduce the degree of lipid peroxidation and increase the activity of SOD and CAT and the total anti-oxidative stress in rat central nervous system during oxidative stress injury induced by obstructive jaundice. High doses of MK-801 Compared with the low dose of MK-801 compared to its effect did not significantly increase, but to T-SOD activity lower than the low dose group. The specific mechanism needs further study.