MK-801对锰中毒大鼠脑纹状体NMDA受体亚单位表达的影响  

Effect of MK-801 on Expression of NMDA Receptors Subunit in Manganism Rat Striatum

作　　者：徐斌[1] 徐兆发[1] 邓宇[1] 辛辛[1] 邓小强[1] 高健[1] 

机构地区：[1]中国医科大学公共卫生学院环境卫生学教研室,辽宁沈阳110001

出　　处：《实用预防医学》2009年第3期635-638,共4页Practical Preventive Medicine

基　　金：国家自然科学基金项目(编号:30771834)

摘　　要：目的研究MK801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／kgMK-801，2h后皮下注射200μmol／kg的氯化锰溶液；注射容量均为5ml/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、NR2BmRNA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 study the effect of MK - 801 on expression of NMDA receptors subunit mRNAs and proteins in manganism rat striatum. Methods The 40 Wistar rats were divided into five groups by weight at random （each n= 5）. The first group was the control group which was given subcutaneous （s. c. ） injection of 0.9 % NaCI. The second to fourth groups were respectively given s.c. injection of 8, 40, 200 μmol/kg MnCI2. The fifth group was MK - 801 pre - treatment group which was given intraperitoneal injection of 0.3 μmol/kg every two - day, two hour before the s.c. administration with 200 μmol/kg MnCl2. The capacity of injection was all 5 ml/kg. 4 weeks after administration, the rats were anatomized to get the tissue samples of the striatum. The levels of Glu, Mn, and expression of NRI, NR2A and NR2B mRNAs and proteins in rat stri- atum were determined. Neurocytes apoptosis in rat striatum was examined by electron microscopy. Results The results showed that with the increase of administered- MnCI2 dosage, Glu concentration and Mn concentration in striatum were increased. The RT - PCR and Western Blotting results showed that the levels of NR1, NR2A and NR2B mRNA and proteins were reduced in different extent compared with those of control group. Expression of NR2A mRNA and protein were much more sen- sitive to Mn than those of NR1 and NR2B. Under transmission electron microscopy, neurocytes showed features of apoptosis; characterized by nucleus shrinkage, dense aggregation of chromatin and chromatin margination. Compared with 200 lamol/kg MnCl2 group, MK- 801 pre- treatment could increase expression of NR2A mRNAs and proteins （P〈 0.05）. Conclusions Exposure to Mn could induce neurocytes apoptesis by influencing the glutamate metabolism and inhibiting expression of NR1, NR2A and NR2B mRNAs and proteins in rat striatum. MK - 801 pre - treatment could increase expression of NR2A mRNAs and proteins.

关 键 词：锰 NMDA受体 神经细胞凋亡 纹状体 

分 类 号：R994.6[医药卫生—毒理学]