【作者】 敬海明； 刘建中； 高文晖； 赵超英； 马玲； 李国君；

【Author】 JING Hai-ming~(1,2),LIU Jiang-zhong~2,GAO Wen-hui~2,ZHAO Chao-ying~2,MA Ling~2,LI Guo-jun~(1,2*) 1.School of Public Health and Family Medicine,Capital Medical University, Beijing,100069 2.Beijing Centers for Disease Control and Prevention/Beijing Research Center for Preventive Medicine,Beijing 100013,China

【机构】 首都医科大学公共卫生与家族医学学院； 北京市疾病预防控制中心/北京市预防医学研究中心；

【摘要】 锰是机体所必需的一种微量元素,但过量暴露时又会引起症状上类似于帕金森氏病的神经毒性,对于其机制的探讨,一直以来都是人们研究的热点。尤其是近年来,甲基环戊二烯三羰基锰(Methyl-cyclopentadienyl-Manganese-Tricarbonyl,MMT)作为汽油添加剂的使用而引起的大气锰污染日益严重,逐渐引起国内外学者对长期低剂量锰暴露研究的重视。本研究即探讨锰对大鼠中枢神经系统血-脑脊液屏障(blood-cerebrospinal fluid barrier,BCB)的毒性损伤作用。通过无水氯化锰腹腔注射((6mg Mn/kg B·W)建立不同病程(30天、90天及90天后无处理观察30天)的锰中毒动物模型,各时间点染毒结束后采集血清与CSF样本及提取侧脑室的脉络丛(choroid plexus,CP)组织,溴甲酚绿法和ELISA法检测各组大鼠血清与CSF中白蛋白水平,计算出CSF白蛋白指数,并与相应对照组进行比较,光学显微镜与电子显微镜下检测大鼠CP组织的病理形态学改变。结果表明:30天染毒组、90天染毒组及有30天恢复期的90天染毒组CSF白蛋白、CSF白蛋白指数均明显高于其相应的对照组(P<0.05),并且30天染毒组CSF白蛋白、CSF自蛋白指数低于90大染毒组与有30天恢复期的90天染毒组(P<0.05),90天染毒组CSF白蛋白、CSF白蛋白指数低于有30天恢复期的90染毒组,但无统计学意义(P>0.05)。光镜和电镜观察发现,染锰导致CP上皮细胞形状不规则,微绒毛结构紊乱、缩短;胞浆内出现空泡、核质凝聚,线粒体结构破坏,细胞间连接部分断裂或消失等,随染锰时间的延长有加重的趋势,并且脱离锰接触30天后仍表现为进行性加重。由研究结果可推论得出,锰可以引起脉络丛组织病理形态学改变,具有时效性与不可逆性的特征;CSF白蛋白及CSF白蛋白指数与CP的损伤程度呈正相关,可以作为判断BCB损伤程度的参考指标。更多还原

【Abstract】 Long-term exposure to high levels of manganese(Mn) results in a neurological disorder, named manganism,by mechanisms not completely understood.To investingate the effect and degree of the toxicity damage on rat’s choroid plexus(CP,i.e.,blood-cerebrospinal fluid barrier,BCB) after giving anhydrous manganese chloride(i.p.6 mg Mn/kg B·W) for 30 days,90 days and 90 days followed by 30 days recovery.The samples of serum,cerebrospinal fluid(CSF),CP of lateral ventricles were collected at each time point.The level of albumin in serum and CSF were determined by using the methods of bromcresol green(BCG) and ELISA,respectively.Pathomorphological changes of CP cells were observed in light microscopy and electron microscopy.The results showed that the levels of CSF albumin and CSF albumin index in the three manganese-treated groups were obviously higher than those of their related control groups(P<0.05).The CSF albumin and CSF albumin index of the 30 days manganese- treated group was lower than the other manganese-treated groups(P<0.05),and those of 90 days manganese-treated group was slightly lower than the 90 days manganese-treated followed by 30 days recovery group(P>0.05).Light microscopy and transmission electron microscopy revealed that Mn exposure resulted in flattened and shrunken cell layer,cytoplasmic vacuolation,nuclei and chromosome condensation,mitochondrion destruction microvilli shortening and partia disconnection in intracellular junctions between two adjacent epithelial cells The structural alteration was mild after day treated and moderate in day treate Noticeably the intracellular damage after day convalescence was even worse than that at days suggesting a long lasting pathological damage even after Mn exposure was ceased In conclusion manganese could induce the pathological changes of CP,and the changes degree is positively time variation and irreversibility.The levels of CSF albumin and CSF albumin index correlate with the extent of injury,and potentially have an important value in judgement of BCB impairment after manganese exposure.更多还原