表皮生长因子受体抑制剂对孕期感染仔鼠脑损伤的治疗作用及机制研究

Therapeutic effect and mechanism of EGFR inhibitor on brain injury in infected fetal rat during pregnancy

目的 探究表皮生长因子受体(EGFR)抑制剂C225对孕期感染的仔鼠脑损伤的治疗作用及机制。方法 通过腹腔注射LPS构建孕期感染仔鼠脑损伤模型,同时给予孕鼠C225(250 nm)治疗,采用试剂盒检测仔鼠脑组织中炎症因子及氧化应激标志物的含量,通过PCR检测M1及M2型小胶质细胞标志物含量,通过Western blot检测EGFR磷酸化及蛋白表达水平。结果 在LPS诱导的孕期感染仔鼠脑损伤中,仔鼠脑组织炎症因子含量增加,氧化应激水平升高,M1型小胶质细胞标志物含量升高,M2型小胶质细胞标志物含量降低。EGFR磷酸化及蛋白表达水平升高。C225能够降低LPS诱导的孕期感染仔鼠脑组织中炎症因子的含量和氧化应激水平,降低M1型小胶质细胞标志物的含量,增加M2型小胶质细胞标志物的含量,降低EGFR磷酸化及蛋白表达水平。结论 EGFR抑制剂C225通过抑制M2型小胶质细胞向M1型的转换,缓解LPS诱导的孕期感染仔鼠脑损伤。

Objective To explore the therapeutic effect and mechanism of C225,an EGFR inhibitor,on the brain injury of fetal rats infected during pregnancy.Methods The brain injury model of infected fetal rat during pregnancy was established by intraperitoneal injection of LPS.The pregnant rats were treated with C225(250 nm).The content of inflammatory factors and oxidative stress markers in brain tissue of fetal rats were detected by the kit.The content of M1 and M2 microglial markers was detected by PCR,The phosphorylation and protein expression of EGFR were detected by Western blot.Results In LPS-induced brain injury of the fetal of pregnant rats,the content of inflammatory factors in the brain tissue of the fetal rats increased,and the level of oxidative stress increased.The content of M1 microglia markers increased,while M2 microglia markers decreased.The level of EGFR phosphorylation and protein expression increased.C225 reduced the content of inflammatory factors and the level of oxidative stress in the brain tissue of LPS-induced fetal rat infected during pregnancy,C225 reduced the content of M1 microglial markers and increased the content of M2 microglial markers.C225 decreased the phosphorylation and protein expression of EGFR in the brain of fetal rats.Conclusion The EGFR inhibitor C225 alleviates LPS-induced brain injury in pregnant infected fetal rats by inhibiting the conversion of M2 microglia to M1.