mGluR5拮抗剂MPEP调控MAPK信号通路缓解大鼠子痫前期脑损伤  

m Glu R5 antagonist MPEP alleviates preeclampsia brain damage via MAPK signaling pathway in rat

作　　者：葛静 单莉莉 宋平平 赵红艳 张金环 GE Jing;SHAN Li-li;SONG Ping-ping;ZHAO Hong-yan;ZHANG Jin-huan(Department of Gynecology and Obstetrics,The Second Affiliated Hospital of Shenyang Medical CollegeLiaoning Veterans General Hospital,Shenyang 110002;Department of Gynecology and Obstetrics,General Hospital of Northern Theater Command,Shenyang 110016)

机构地区：[1]沈阳医学院附属第二医院·辽宁省退役军人总医院妇产科,辽宁沈阳110002 [2]北部战区总医院妇产科,辽宁沈阳110016

出　　处：《解剖科学进展》2021年第2期186-190,共5页Progress of Anatomical Sciences

基　　金：国家重点研发计划(2018YFC1002700,2018YFC1002703);辽宁省自然科学基金(2019-ZD-1059)。

摘　　要：目的探讨mGluR5拮抗剂MPEP缓解大鼠子痫前期脑损伤的作用。方法 SPF级妊娠大鼠被随机分为6组,妊娠对照组(PN)、妊娠同型半胱氨酸组(PH)、PH+神经递质mGluR5受体拮抗剂MPEP组(PHM)、PHM+U0126组、PHM+SB202190组及PHM+SP600125组,于妊娠第10天,PH组每日腹腔内注射同型半胱氨酸200 mg/kg以制备子痫前期模型;PHM组每日腹腔皮下注射神经递质mGluR5受体拮抗剂MPEP(1.5mg/kg);PHM+U0126组,PHM+SB202190组,PHM+SP600125组,在MPEP注射前1 h,分别腹腔注射U0126(4mg/kg),SB202190(20 mg/kg)和SP600125(30 mg/kg)共计10天。检测各组大鼠血压、尿蛋白;氧化应激水平;炎症因子释放量;并检测了MAPK信号通路相关蛋白ERK1/2,p38 MAPK,JNK,p-ERK1/2,p-p38 MAPK及p-JNK蛋白表达。结果 MPEP降低大鼠血压及尿蛋白含量,增加NO、NOS、SOD及GSH-Px活性,并抑制炎症因子IL-1、IL-6及TNF-α的水平;同时,MPEP能够抑制ERK1/2,p38 MAPK,JNK蛋白的磷酸化;但MPEP的上述作用被U0126,SB202190及SP600125所阻断。结论 mGluR5拮抗剂MPEP对子痫前期导致的大鼠脑损伤与调控MAPK信号通路相关。Objective To investigate the effect of mGluR5 antagonist MPEP in alleviating preeclampsia brain injury in rats. Methods Pregnant rats of SPF grade were randomly divided into 6 groups: pregnancy control group(PN), pregnancy homocysteine group(PH), PH+ neurotransmitter mGluR5 receptor antagonist MPEP group(PHM), PHM+U0126 group, PHM+ SB202190 group and PHM+SP600125 group. On the 10 th day of pregnancy, homocysteine 200 mg/kg was injected into the abdominal cavity of PH group daily.PHM group received intraperitoneal subcutaneous injection of neurotransmitter mGluR5 receptor antagonist MPEP(1.5 mg/kg). The blood pressure, urinary protein, oxidative stress level, inflammatory factor release, and the expression of ERK1/2, p38 MAPK, JNK, p-ERK1/2, p-p38 MAPK and p-JNK proteins were detected. Results MPEP decreased blood pressure and urinary protein content, increased NO, NOS, SOD and GSHPx activity, and inhibited the levels of inflammatory factors IL-1, IL-6 and TNF-alpha, inhibited phosphorylation of ERK1/2, p38 MAPK and JNK proteins. However, the above effects of MPEP were blocked by U0126, SB202190 and SP600125. Conclusion The effect of mGluR5 antagonist MPEP on the brain injury induced by preeclampsia via MAPK signaling pathway in rats.

关 键 词：妊娠期高血压疾病 子痫前期 MGLUR5 MPEP MAPK信号通路 大鼠 

分 类 号：R776.1[医药卫生—眼科]