神经调节素1对铅中毒小鼠脑前额叶皮层细胞凋亡的影响

Effects of neuregulin1 on apoptosis in prefrontal cortex of lead poisoning mice

目的研究神经调节素1(neuregulin1,NRG1)对铅中毒小鼠脑内细胞凋亡的影响。方法选择60只健康4月龄SPF级C57bl/6雄性小鼠采用腹腔注射方式染毒乙酸铅(30 mg/kg),隔日注射1次,共注射7次。铅中毒模型建立后,将小鼠随机分成6组,分别为对照组和低(20 ng/kg)、中(50 ng/kg)、高(100 ng/kg)剂量NRG1处理组及NRG1(50 ng/kg)+Wortmannin(PI3K抑制剂,0.01 nmol)组、NRG1(50 ng/kg)+Wortmannin(0.05 nmol)组,其中,NRG1采用腹腔注射方式染毒,连续染毒14 d;Wortmannin在NRG1处理的第1天采用右侧脑室一次性注射染毒。检测小鼠前额叶皮层ErbB4和Bax的表达变化、DNA凋亡情况及p-Akt蛋白的表达情况。结果与对照组相比,NRG1处理组的ErbB4阳性细胞计数和荧光强度、p-Akt表达水平增高,而Bax细胞数和DNA碎片表达减少,差异有统计学意义(P<0.05)。与50 ng/kg NRG1处理组相比,NRG1+Wortmannin组小鼠前额叶皮层ErbB4细胞数和荧光强度、p-Akt蛋白表达明显减少,Bax细胞数和DNA碎片增加,差异有统计学意义(P<0.05)。结论 NRG1可通过上调ErbB4和p-Akt的表达,拮抗铅中毒引起的小鼠前额叶皮层细胞凋亡。

Objective To investigate the effects of neuregulin1（NRG1） on the apoptosis in PbAc-exposed mice and relevant mechanism. Methods PbAc-exposed mice were divided into six groups randomly：control group,low-dose NRG1-treated group（20 ng/kg）,median-dose NRG1-treated group（50 ng/kg）,hige-dose NRG1-treated group（100 ng/kg）,NRG1（50 ng/kg）＋Wortmannin（PI3K inhibitor, 0.01 nmol） group,NRG1（50 ng/kg）＋Wortmannin（0.05 nmol）group. NRG1 was given by peritoneal injection for 14 days. Wortmannin was administrated through the right lateral ventricle injection for once of 10 μl. The expression of ErbB4 and Bax, the levels of apoptosis and Akt and p-Akt protein were tested. Results Compared with control group, the expression of ErbB4 and p-Akt increased,the levels of Bax and DNA fragmentation decreased in NRG1-treated group（P〈0.05）. Compared with 50 ng/kg NRG1-treated group, the expression of ErbB4 and p-Akt protein decreased,the levels of Bax and DNA fragmentation increased in NRG1＋Wortmannin-treated group（P〈0.05）. Conclusion Conclusion NRG1 may exert anti-apoptosis effects induced by PbAc through the upregulation of the level of ErbB4 and p-Akt.