VU0360172激活mGluR5对新生大鼠生发基质出血的保护作用  

Stimulation of mGluR5 by VU0360172 protected against germinal matrix hemorrhage in neonatal rats

作　　者：王筱雅 冯占辉 熊英 张晴 杨清 陈惠心 汪朝云 左丁 叶兰 WANG Xiao-ya;FENG Zhan-hui;XIONG Ying;ZHANG Qing;YANG Qing;CHEN Hui-xin;WANG Zhao-yun;ZUO Ding;YE Lan(Dept of Pharmacology, Basic Medical College, Guizhou Medical University;Dept of Neurology, Affiliated Hospital of Guizhou Medical University;The Functional Science Laboratory, Basic Medical College, Guizhou Medical University, Guiyang 550025, China)

机构地区：[1]贵州医科大学基础医学院药理学教研室,贵州贵阳550025 [2]贵州医科大学附属医院神经内科,贵州贵阳550025 [3]贵州医科大学基础医学院机能学实验室,贵州贵阳550025

出　　处：《中国药理学通报》2022年第7期1000-1004,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81960224)。

摘　　要：目的研究VU0360172激活代谢型谷氨酸受体5(metabotropic glutamate receptor 5,mGluR5)对新生大鼠生发基质出血(germinal matrix hemorrhage,GMH)产生的保护作用,并探讨其作用机制。方法7日龄SD大鼠随机分为假手术组、模型组、VU0360172低、中、高剂量组。颅内注射胶原酶Ⅶ-S建立乳鼠GMH模型,术后3 h腹腔注射不同剂量VU0360172,假手术组、模型组给予等容积溶剂;术后24 h对乳鼠进行神经行为学测试,测定脑含水量、脑血红蛋白含量,HE染色观察乳鼠脑部组织病理学,Western blot法检测Bcl-2、cleaved-caspase-3蛋白表达。结果与假手术组相比,模型组神经行为学测试消耗时间增加,评分升高(P<0.01),脑含水量、脑血红蛋白含量增加(P<0.01),患侧脑组织损伤显著,Bcl-2蛋白表达下调(P<0.05),cleaved-caspase-3蛋白表达上调(P<0.01);与模型组相比,VU0360172给药组神经测试时间缩短,评分降低(P<0.05),脑含水量、脑血红蛋白含量均降低(P<0.05),患侧脑组织损伤减轻,Bcl-2蛋白表达增加(P<0.05),cleaved-caspase-3蛋白表达减少(P<0.01)。结论VU0360172激动mGluR5对乳鼠生发基质出血具有保护作用。Aim To investigate the protective effect of mGluR5 activated by VU0360172 on germinal matrix hemorrhage in neonatal rats.Methods Seven day-old SD rats were randomly divided into Sham,GMH,and low-,medium-,and high-dose groups.The model was established by intracerebral injection of collagenaseⅦ-S.Then three doses of VU0360172 were injected intraperitoneally 3 h after surgery.Sham and GMH group were given the same amount of solvent.Neurobehavioral tests were performed 24 h after surgery.Then the brain tissues were collected for evaluation of brain water content,brain hemoglobin content and HE staining.The expressions of Bcl-2 and cleaved-caspase-3 were determined by Western blot.Results Compared with Sham,GMH group had pooler behaviors in neurofunctional tests with increased brain water content and brain hemoglobin content(P<0.01).And brain tissues were destroyed significantly.WB results showed the expression level of Bcl-2 decreased(P<0.05),while cleaved-caspase-3 being up-regulated(P<0.01).However,the administration of VU0360172 improved neurological function and ameliorated brain edema and hemorrhage(P<0.01).Brain pathological damage was reduced.Moreover,the stimulation of mGluR5 up-regulated Bcl-2 protein expression(P<0.05)and decreased the level of cleaved-caspase-3(P<0.01).Conclusion Activation of mGluR5 by VU0360172 protects against germinal matrix hemorrhage in neonatal rats.

关 键 词：MGLUR5 生发基质出血 VU0360172 细胞凋亡 Bcl-2 CASPASE-3 

分 类 号：R-332[医药卫生] R322.81R329.25R392.11R722