砷对仔代大鼠脑组织氧化损伤及超微病理结构的影响  

Arsenic-induced Oxidative Damage and Histopathological Changes in Brain of Rat Offspring

作　　者：席淑华[1] 孙贵范[1] 孙文娟[2] 王凤芝[2] 金亚平[1] 

机构地区：[1]中国医科大学公共卫生学院,辽宁沈阳110001 [2]沈阳医学院,辽宁沈阳110034

出　　处：《工业卫生与职业病》2008年第2期89-93,共5页Industrial Health and Occupational Diseases

基　　金：国家自然科学基金(30571590)

摘　　要：目的观察砷对仔代大鼠生长发育不同时期脑组织氧化应激状态影响和脑组织病理学变化,探讨砷致脑损伤的机制。方法雌性大鼠于受孕后第6天开始以自由饮水方式分别暴露10、50和100 mg/L的NaAsO2水溶液,连续染毒直到仔鼠出生后第42天,分别于仔鼠出生后第12小时、第28天、第42天处死仔鼠,取大脑皮质、海马结构进行氧化性指标测定,并在第42天观察仔鼠大脑皮质病理形态学变化。结果仔鼠出生后第12小时,100 mg/L砷染毒组脑组织中丙二醛(MDA)含量〔(7.23±2.32)nmol/(mg.Pr)〕明显高于对照组〔(4.58±0.95)nmol/(mg.Pr)〕,出生后第28天、第42天,100 mg/L砷染毒组大脑皮质MDA含量明显升高,而海马结构中MDA在各组间比较,差异无显著性。脑中抗氧化物质谷胱甘肽(GSH)含量在仔鼠出生后第12小时、第28天,各砷染毒组均未发生显著改变,但在出生后第42天100 mg/L砷染毒组仔鼠大脑皮质〔(21.57±12.55)mg/(g.Pr)〕、海马结构〔(21.55±10.59)mg/(g.Pr)〕中GSH含量均明显低于对照组〔(36.20±4.59)mg/(g.Pr)〕、〔(39.38±20.65)mg/(g.Pr)〕,并且抗氧化酶谷胱甘肽过氧化酶(GSH-Px)活力也呈明显降低趋势。脑组织的透射电镜观察显示50 mg/L砷染毒组仔鼠脑组织神经元呈空泡变,核染色质聚积于核膜下,核肿胀,呈水样变性。100 mg/L砷染毒组仔鼠脑组织神经元内质网极度扩张,游离核糖体消失。结论砷可以通过胎盘屏障进入仔鼠体内,并可透过血脑屏障引起脑组织脂质过氧化,从而破坏脑组织生物膜结构引起一系列生理病理改变。Objective To observe the oxidative damage and histopathological changes in the brain of rat offspring in different development period induced by inorganic arsenic exposure via drinking water. Methods Wistar rats were exposed to 10, 50, 100 mg/L NaAsO2 respectively in drinking water from gestation day 6 until F1 pups 42 days old. Arsenic-induced alteration in oxidative and antioxidant defense system, malondialdehyde （ MDA）, glutathione （GSH） level and activity of enzymes-glutathione peroxidase （GSH-Px）in rat brain regions such as cortex and hippocampus were separately examined when F1 pups were 12 hours, 28, 42 days old. Histopathological changes of rat brain were observed in F1 pups 42 days old. Results MDA level（7.2342.32）nmol/ （mg · Pr） 100 mg/L group F1 pups brain was higher than that of control rats（4. 5840. 95）nmol/ （mg · Pr） the postnatal 12 hours. On the postnatal day 28 and 42, MDA levels in 100 mg/L group F1 pups cortex were also higher than that of control rats, but the difference in hippocampus was not observed. 42 day exposure to arsenic caused significant reduction of GSH on cortex （21. 57±12. 55）mg/ （g· Pr） andhippocampus（21.55410.59）mg/ （g·Pr） and GSH-Pxon hippocampus （5. 5444.59）U/ml in 100 mg/L arsenic group compared to control rats（36. 20±4. 59）mg/ （g · Pr）, （39.38 420. 65）mg/ （g · Pr）, （10. 06±7.05）U/ml. However, the changes of GSH level and GSH-Px activities in pups＇ rat brain had not been seen on the postnatal 12 hours, the postnatal day 28. Ultrastructural pathological changes of cortex showed vacuolar degeneration of neurons, karyotin aggregating the side of karyotheca, nuclear swell and hydropic change hydropic degeneration in 50 mg/L NaAsO2 rats, and neurons endoplasmic reticulum extremely dilated, free-ribosome disappeared in 100 mg/L rats. Conclusions Inorganic arsenic could penetrate placental barrier and hematoencephalic barrier to induce deficits in antioxidant enzyme activities and increase in lipid perox

关 键 词：大鼠 氧化性损伤 病理改变 亚砷酸钠 

分 类 号：R114[医药卫生—卫生毒理学]