Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various disea...Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.展开更多
本研究旨在探索DHRS7C基因外显子多态性及其与阳原驴体尺性状的相关性。基于课题组前期阳原驴的体尺性状全基因组关联分析(Genome-wide Association Study,GWAS)结果,选择DHRS7C(Dehydrogenase/Reductase Member 7C)为候选基因,通过PCR...本研究旨在探索DHRS7C基因外显子多态性及其与阳原驴体尺性状的相关性。基于课题组前期阳原驴的体尺性状全基因组关联分析(Genome-wide Association Study,GWAS)结果,选择DHRS7C(Dehydrogenase/Reductase Member 7C)为候选基因,通过PCR扩增其外显子区域、Sanger测序、基因分型以及关联分析等方法,寻找与阳原驴体尺性状显著相关的SNP位点。对显著位点突变前后的mRNA二级结构,蛋白质二、三级结构进行预测比对。结果表明:阳原驴DHRS7C基因外显子区域内存在g.12389830 G>A突变,产生GG、GA 2种基因型,不同基因型个体之间的体长、胸围、管围差异不显著,体高差异显著,GA基因型个体体高显著高于GG基因型;该突变造成蛋白质第63位精氨酸变为赖氨酸,形成错义突变,通过在线网站结构预测,突变前后mRNA二级结构,蛋白质二、三级结构均无明显变化;同时,研究发现该基因还存在g.12397240 G>A、g.12397287 G>A、g.12398389 G>A、g.12398466 G>A 4个突变,但在本研究驴群中尚未发现它们与体尺性状存在显著相关性。综上所述,DHRS7C基因外显子3区域中的SNP(g.12389830 G>A)位点可作为阳原驴体高性状的潜在分子标记。展开更多
基金supported by National Natural Science Foundation of China,No.32102745(to XL).
文摘Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.
