孤束核Phox2b神经元参与呼吸调控的研究
发布时间：2020-12-12 19:23
睡眠呼吸障碍疾病是一组发生在睡眠状态下的呼吸异常疾病,包括阻塞性睡眠呼吸暂停、中枢性睡眠呼吸暂停和睡眠相关性肺泡低通气等。其中,先天性中枢性低通气综合征（congenital central hypoventilation syndrome,CCHS）是一种罕见的遗传性睡眠呼吸障碍综合征,其主要特征是新生儿在入睡后出现严重的肺泡低通气,需要借助呼吸机维持通气。机体发生肺泡低通气时,对高碳酸和低氧的敏感性降低甚至丧失,最终造成呼吸衰竭。基因测序结果显示,90%以上的CCHS病人有paired-like homeobox 2b（Phox2b）基因突变。Phox2b基因位于第4对常染色体上,其编码的蛋白质主要参与胚胎期自主神经系统的发育。Phox2b表达在呼吸反射的传入通路上,包括颈动脉体（carotid body,CB）、孤束核（nucleus tractus solitarii,NTS）、斜方体后核（retrotrapezoid nucleus,RTN）和蓝斑核（locus coeruleus）等。中枢呼吸化学感受器反射通过感受细胞外液中CO2/H+
【文章来源】：河北医科大学河北省
【文章页数】：131 页
【学位级别】：博士
【部分图文】：
Phox2b-Cre转基因小鼠的鉴定Fig.1ValidationofPhox2b-CremouselineA,gelimageshowinggenotypingofPhox2b-Cremice.300and700bpforheterozygousgeneand300bponlyforwildtype.B,immunofluorescence
图 3 CNO 激活表达 mCherry 的 Phox2b 神经元Fig.3 CNO activates mCherry-transduced Phox2b neuronsA-F, images showing activation of mCherry-transduced Phox2b neurons byCNO (D-F) rather than saline (A-C). Scale bar = 25 μm. G, the number ofCNO-stimulated cFos+mCherry+neurons were far greater compared with thatstimulated by saline. n = 5 mice,****P < 0.0001 by unpaired t test. H-I,whole-cell patch clamp recordings from Phox2b-Cre mice transfected withhM3Dq-mCherry showed that CNO (30 μM) produced a rapid reversibledepolarization of membrane potential. n = 9,***P < 0.001 by a two-tailedpaired t test.
图 4 激活 Phox2b 神经元对清醒小鼠呼吸功能的影响Fig.4 Effect of chemogenetic activation of Phox2b-expressing neurons on lungfunction in awake miceA-C, pulmonary function tests showing that compared with the Saline group,the respiratory frequency (A) and MV (C) increased significantly afteradministration of CNO, whereas the TV (B) remained unchanged in bothgroups. n = 32 mice,*P < 0.05,***P < 0.001,****P < 0.0001 vs. Saline group bytwo-way ANOVA with Bonferroni's post hoc test. D-F, application of neitherCNO nor saline caused significant changes in breathing parameters when micewere microinjected the control vector AAV-EF1α-DIO-mCherry. n = 10 micefor each group.
本文编号：2913141
【文章来源】：河北医科大学河北省
【文章页数】：131 页
【学位级别】：博士
【部分图文】：
Phox2b-Cre转基因小鼠的鉴定Fig.1ValidationofPhox2b-CremouselineA,gelimageshowinggenotypingofPhox2b-Cremice.300and700bpforheterozygousgeneand300bponlyforwildtype.B,immunofluorescence
图 3 CNO 激活表达 mCherry 的 Phox2b 神经元Fig.3 CNO activates mCherry-transduced Phox2b neuronsA-F, images showing activation of mCherry-transduced Phox2b neurons byCNO (D-F) rather than saline (A-C). Scale bar = 25 μm. G, the number ofCNO-stimulated cFos+mCherry+neurons were far greater compared with thatstimulated by saline. n = 5 mice,****P < 0.0001 by unpaired t test. H-I,whole-cell patch clamp recordings from Phox2b-Cre mice transfected withhM3Dq-mCherry showed that CNO (30 μM) produced a rapid reversibledepolarization of membrane potential. n = 9,***P < 0.001 by a two-tailedpaired t test.
图 4 激活 Phox2b 神经元对清醒小鼠呼吸功能的影响Fig.4 Effect of chemogenetic activation of Phox2b-expressing neurons on lungfunction in awake miceA-C, pulmonary function tests showing that compared with the Saline group,the respiratory frequency (A) and MV (C) increased significantly afteradministration of CNO, whereas the TV (B) remained unchanged in bothgroups. n = 32 mice,*P < 0.05,***P < 0.001,****P < 0.0001 vs. Saline group bytwo-way ANOVA with Bonferroni's post hoc test. D-F, application of neitherCNO nor saline caused significant changes in breathing parameters when micewere microinjected the control vector AAV-EF1α-DIO-mCherry. n = 10 micefor each group.
本文编号：2913141
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