孤束核Phox2b神經(jīng)元參與呼吸調(diào)控的研究
發(fā)布時間：2020-12-12 19:23
睡眠呼吸障礙疾病是一組發(fā)生在睡眠狀態(tài)下的呼吸異常疾病,包括阻塞性睡眠呼吸暫停、中樞性睡眠呼吸暫停和睡眠相關(guān)性肺泡低通氣等。其中,先天性中樞性低通氣綜合征（congenital central hypoventilation syndrome,CCHS）是一種罕見的遺傳性睡眠呼吸障礙綜合征,其主要特征是新生兒在入睡后出現(xiàn)嚴(yán)重的肺泡低通氣,需要借助呼吸機維持通氣。機體發(fā)生肺泡低通氣時,對高碳酸和低氧的敏感性降低甚至喪失,最終造成呼吸衰竭。基因測序結(jié)果顯示,90%以上的CCHS病人有paired-like homeobox 2b（Phox2b）基因突變。Phox2b基因位于第4對常染色體上,其編碼的蛋白質(zhì)主要參與胚胎期自主神經(jīng)系統(tǒng)的發(fā)育。Phox2b表達(dá)在呼吸反射的傳入通路上,包括頸動脈體（carotid body,CB）、孤束核（nucleus tractus solitarii,NTS）、斜方體后核（retrotrapezoid nucleus,RTN）和藍(lán)斑核（locus coeruleus）等。中樞呼吸化學(xué)感受器反射通過感受細(xì)胞外液中CO2/H+
【文章來源】：河北醫(yī)科大學(xué)河北省
【文章頁數(shù)】：131 頁
【學(xué)位級別】：博士
【部分圖文】：
Phox2b-Cre轉(zhuǎn)基因小鼠的鑒定Fig.1ValidationofPhox2b-CremouselineA,gelimageshowinggenotypingofPhox2b-Cremice.300and700bpforheterozygousgeneand300bponlyforwildtype.B,immunofluorescence
圖 3 CNO 激活表達(dá) mCherry 的 Phox2b 神經(jīng)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.
圖 4 激活 Phox2b 神經(jīng)元對清醒小鼠呼吸功能的影響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.
本文編號：2913141
【文章來源】：河北醫(yī)科大學(xué)河北省
【文章頁數(shù)】：131 頁
【學(xué)位級別】：博士
【部分圖文】：
Phox2b-Cre轉(zhuǎn)基因小鼠的鑒定Fig.1ValidationofPhox2b-CremouselineA,gelimageshowinggenotypingofPhox2b-Cremice.300and700bpforheterozygousgeneand300bponlyforwildtype.B,immunofluorescence
圖 3 CNO 激活表達(dá) mCherry 的 Phox2b 神經(jīng)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.
圖 4 激活 Phox2b 神經(jīng)元對清醒小鼠呼吸功能的影響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.
本文編號：2913141
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