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目的研究MK-801对锰中毒大鼠脑纹状体NMDA受体亚单位mRNA和蛋白表达的影响。方法Wistar大鼠40只,按体重随机分成5组,每组8只。第1组为对照组,皮下注射0.9%氯化钠;第2~4组为锰染毒组,分别皮下注射8、40、200μmol/kg的氯化锰溶液;第5组为MK-801预处理组,隔日腹腔注射0.3μmol/kg MK-801,2 h后皮下注射200μmol/kg的氯化锰溶液;注射容量均为5 ml/kg,染锰4周,每周5次。通过电镜观察神经细胞损伤情况,同时测定脑纹状体锰和谷氨酸(Glu)含量,NR1、NR2A、NR2B mRNA和蛋白表达。结果染锰4周后,随着染锰剂量的增加,纹状体Mn和Glu含量均逐渐升高;NR1、NR2A、NR2B的mRNA和蛋白表达均有不同程度的下降,其中NR2A灰度值下降最明显。电镜观察发现染锰后神经细胞出现不同程度的空泡变性和染色质边集。MK-801预处理组与高剂量染锰组比较,NR2A的mRNA和蛋白表达均有所增加(P<0.05)。结论锰能够破坏纹状体Glu平衡,并且抑制NMDA受体亚单位的表达产生神经毒性,促使细胞凋亡。MK-801可以影响NR2A的mRNA和蛋白表达。
Objective To investigate the effect of MK-801 on NMDA receptor subunit mRNA and protein expression in brain of rats with manganese poisoning. Methods Forty Wistar rats were randomly divided into 5 groups according to body weight, with 8 rats in each group. The first group was control group, subcutaneous injection of 0.9% sodium chloride; the second to the fourth group for the manganese exposure group were subcutaneous injection of 8,40,200μmol / kg of manganese chloride solution; the fifth group of MK-801 pre The rats in the treatment group were injected intraperitoneally with 0.3μmol / kg MK-801 every other day for 2 hours and then subcutaneously injected with 200μmol / kg manganese chloride solution. The injection volume was 5 ml / kg, and manganese was dyed for 4 weeks for 5 times a week. The damage of nerve cells was observed by electron microscope. The contents of Mn and Glu in brain striatum and the expressions of NR1, NR2A and NR2B mRNA and protein were determined. Results After 4 weeks of manganese exposure, the content of Mn and Glu in striatum increased gradually with the increase of manganese dose. The mRNA and protein expressions of NR1, NR2A and NR2B all decreased to different extents. The grayscale value of NR2A decreased The most obvious. Electron microscopy showed different degrees of vacuolar degeneration and chromatin margination in the post-Mn-dyed nerve cells. The mRNA and protein expressions of NR2A in MK-801 pretreatment group were significantly increased compared with those in high-dose manganese group (P <0.05). Conclusion Manganese can destroy the striatum Glu balance and inhibit the expression of NMDA receptor subunits to produce neurotoxicity and promote apoptosis. MK-801 can affect NR2A mRNA and protein expression.