白果内酯对早产仔鼠WMI的改善作用及其机制  

Improvement effect of ginkgo lactone on WMI in preterm neonatal rats

作　　者：姚娟 赵旸[1] 李娜 秦霞 赵剡[3] YAO Juan;ZHAO Yang;LI Na;QIN Xia;ZHAO Yan(Department of Neonatology;Department of Pediatrics,Shiyan Municipal People′s Hospital,Hubei Medical College,Shiyan,Hubei 442000,China;Department of Emergency,Zhongnan Hospital of Wuhan University,Wuhan,Hubei 430071,China)

机构地区：[1]湖北医药学院附属十堰市人民医院新生儿科,湖北十堰442000 [2]湖北医药学院附属十堰市人民医院儿科,湖北十堰442000 [3]武汉大学中南医院急诊科,武汉430071

出　　处：《重庆医学》2022年第2期204-208,共5页Chongqing medicine

基　　金：湖北省卫生健康委2019年度第一批联合基金立项项目(WJ2019H010)。

摘　　要：目的探讨白果内酯对早产仔鼠脑室周围白质损伤(WMI)的改善作用及其机制。方法对Wistar孕鼠腹腔注射脂多糖致子宫炎症建造早产仔鼠WMI模型,建模仔鼠分为模型组、白果内酯组、激动剂组,另取腹腔注射生理盐水孕鼠作为对照组。白果内酯组、激动剂组分别腹腔注射白果内酯、Ras同源基因(Rho)/Rho相关卷曲螺旋形成蛋白激酶(ROCK)通路激动剂+白果内酯干预,模型组、对照组腹腔注射等体积生理盐水,连续干预2周。采用悬吊实验、斜坡实验、旷场实验检测仔鼠神经行为学,HE染色观察仔鼠侧脑室与脑白质病理学,免疫组化法检测仔鼠少突胶质细胞凋亡情况,Western blot检测仔鼠脑组织Rho/ROCK通路相关蛋白表达。结果模型组、激动剂组、白果内酯组、对照组仔鼠悬吊实验评分逐渐增加、斜坡实验时间逐渐减少、旷场实验评分逐渐增加(P<0.05),侧脑室指数逐渐下降(P<0.05)。模型组脑白质染色淡,结构稀疏,细胞排列紊乱,核固缩;激动剂组、白果内酯组脑白质染色、结构、细胞排列等均明显改善。模型组、激动剂组、白果内酯组、对照组,仔鼠脑白质O4阳性细胞数逐渐增加,p-RhoA、ROCK2、p-MLC2蛋白表达逐渐下降(P<0.05)。结论白果内酯可能通过下调Rho/ROCK通路抑制少突胶质细胞凋亡,减轻早产仔鼠WMI。Objective To investigate the improvement effect of ginkgo lactone on the periventricular white matter injury(WMI)in preterm neonatal rats and its mechanism.Methods The pregnant Wistar rat was intraperitoneally injected by lipopolysaccharide(LPS)to establish the preterm neonatal rat WMI model.The modelled neonatal rats were divided into the model group,ginkgo lactone group and agonist group.The pregnant rats injected by normal saline served as the control group.The ginkgo lactone group and agonist group were intraperitoneally injected by ginkgo lactone and Ras homologous gene(Rho)/Rho associated coiled coil forming protein kinase(ROCK)pathway agonist+ginkgo lactone intervention,the model group and control group were intraperitoneally injected by equal volume of normal saline for consecutive 2 weeks intervention.The suspension test,slope test and open field test were used to detect the neuroethology in the neonatal rats.The HE staining was used to observe the pathological changes of lateral ventricle and cerebral white matter.The apoptosis of oligodendrocytes was detected by immunohistochemistry.Western blot was used to detect the expression of Rho/ROCK pathway related proteins.Results The score of suspension test in the model group,agonist group,ginkgo lactone group and control group was gradually increased,the slope test time was gradually decreased,the open field test score was gradually increased(P<0.05),and the lateral ventricle index was gradually decreased(P<0.05).In the model group,the cerebral white matter staining was light,the structure was sparse,the cell arrangement was disordered,and the nuclear had pyknosis;in the agonist group and ginkgo lactone group,the white matter staining,structure and cell arrangement were significantly improved.The number of O4 positive cells in the white matter of the model group,agonist group,ginkgo lactone group and control group was gradually increased,and the expression levels of p-RhoA,ROCK2 and p-MLC2 proteins were gradually decreased(P<0.05).Conclusion Ginkgo lactone

关 键 词：白果内酯 Ras同源基因/Rho激酶通路 少突胶质细胞 早产 脑白质损伤 

分 类 号：R285.5[医药卫生—中药学]