中文摘要：

目的观察氯化镧（lanthanum chloride,LaCl_3）对大鼠大脑皮质细胞凋亡、葡萄糖调节蛋白（glucose regulated protein,GRP）表达、PKR样内质网激酶（PKR-like endoplasmic reticulum kinase,PERK）和肌醇需求酶1（inositol requiring enzyme 1,IRE1）磷酸化的影响,研究LaCl_3对大脑皮质产生损害效应的机制。方法 32只成年雌性Wistar大鼠随机分为对照组、2.5、5和10 g/L LaCl_3组,2.5、5和10 g/L LaCl_3组妊娠大鼠从受孕起分别饮用2.5、5和10 g/L LaCl_3蒸馏水溶液,对照组妊娠大鼠从受孕起饮用蒸馏水。LaCl_3组子代大鼠断乳前经母鼠胎盘和母乳染镧,断乳后饮用2.5、5和10 g/L LaCl_3蒸馏水溶液1个月。取子代大鼠大脑皮质,以尼氏染色法检测大脑皮质神经细胞尼氏体表达水平,以流式细胞仪法测定大脑皮质神经细胞凋亡率,采用Western blot法检测大脑皮质GRP78、GRP94、PERK、IRE1、磷酸化的PERK（pPERK）和IRE1（pIRE1）及分别受PERK和IRE1调控的生长迟滞和DNA损伤诱导蛋白（growth arrest and DNA damage inducible protein,GADD）153和JUN氨基端激酶（JUN NH2-terminal kinase,JNK）的表达水平。结果各LaCl_3组子代大鼠大脑皮质神经细胞尼氏体表达水平低于对照组（P〈0.05）,而细胞凋亡率高于对照组（P〈0.05）,且均具有一定的剂量-效应关系。2.5 g/L LaCl_3组子代大鼠大脑皮质GRP78、GRP94、pPERK、pIRE1、GADD153和pJNK表达水平高于对照组（P〈0.05）,5 g/L LaCl_3组子代大鼠大脑皮质GRP78、GRP94、pPERK、pIRE1、和GADD153表达水平高于对照和2.5 g/L LaCl_3组（P〈0.05）,10g/L LaCl_3组子代大鼠大脑皮质GRP78、GRP94、pPERK、pIRE1、GADD153和pJNK表达水平高于对照、2.5 g/L和5 g/L LaCl_3组（P〈0.05）。结论 LaCl_3对大鼠大脑皮质的毒性效应机制可能涉及GRP78和GRP94表达上调、PERK和IRE1磷酸化水平升高所致凋亡增多。

英文摘要：

Objective To observe the effects of lanthanum chloride（LaCl_3） on apoptosis, glucose regulated protein（GRP）expression, PKR-like endoplasmic reticulum kinase（PERK） and inositol requiring enzyme 1（IRE1） phosphorylation in the cerebral cortex of rats, and explore the mechanism about LaCl_3-induced damage in the cerebral cortex. Methods A total of 32 adult female Wistar rats were divided into four groups： control, 2.5 g/L, 5 g/L and 10 g/L LaCl_3 groups. The pregnant rats in the 2.5 g/L, 5 g/L and 10 g/L LaCl_3 groups drank 2.5 g/L, 5 g/L and 10 g/L LaCl_3 in distilled water, and control pregnant rats drank distilled water. Pups of LaCl_3 groups were exposed to LaCl_3 by parental placenta and lactation and then drank 2.5 g/L, 5 g/L and 10 g/L LaCl_3 in distilled water for one month. The cerebral cortex samples of pups were used for all detections. The cellular Nissl body levels in the cerebral cortex were detected via Nissl staining. Apoptosis in the cerebral cortex was detected via flow cytometry. The expression levels of GRP78, PERK, phosphorylated PERK（pPERK）, IRE1, phosphorylated IRE1（pIRE1）,growth arrest and DNA damage inducible protein（GADD） 153 and JUN NH2-terminal kinase（JNK） regulated by PERK and IRE1 in the cerebral cortex were analyzed via Western blot. Results The cellular Nissl body levels in the cerebral cortex of three LaCl_3 groups were significantly lower than that of control, but apoptotic rates in the cerebral cortex of three LaCl_3 groups were significantly higher than that of control, and both showed the dose-effect relation. GRP78, GRP94, pPERK, pIRE1,GADD153 and pJNK expression levels in the cerebral cortex of 2.5 g/L LaCl_3 group were significantly higher than those of control（P〈0.05）. GRP78, GRP94, pPERK, pIRE1, GADD153 and pJNK expression levels in the cerebral cortex of 5 g/L LaCl_3 group were significantly higher than those of control and 2.5 g/L LaCl_3 groups（P〈0.05）, and GRP78, GRP94, pPERK, pIRE1,GADD153 and pJNK expression levels in the cer