No abstract

Hypoglossal motoneurons innervate genioglossus muscle, the contraction of which is critical in the maintenance of upper airway patency in patients with obstructive sleep apnea. As a potassium channel distributed in hypoglossal motoneurons, TWIK‐related acid‐sensitive K+ channel‐1 (TASK‐1) could be inhibited by 5‐HT. This study aimed to investigate if TASK‐1 expression in hypoglossal nucleus could be influenced by chronic intermittent hypoxia (CIH) and 5‐HT2A receptors antagonist. Two hundred twenty‐eight rats were exposed to CIH or normoxia (NO) in the presence and absence of 5‐HT 2A receptor antagonist (MDL‐100907) microinjected into the hypoglossal nucleus. The expression of 5‐HT and TASK‐1 in the hypoglossal nucleus were detected by immunohistochemistry and reverse transcription quantitative polymerase chain reaction on the 1st, 3rd, 7th, 14th and 21st day of CIH exposure. The mean optical density (MOD) of 5‐HT in the XII nucleus was significantly increased in the CIH and CIH + MDL group than the NO group on the 7th and 21st day ( p < 0.05). Compared with the NO group, the MOD and gene expression of TASK‐1 in the CIH group was significantly increased on the 7th and 14th day ( p < 0.05), then normalized on the 21st day. The TASK‐1 expression in the CIH + MDL group was significantly lower than the CIH + PBS and CIH group on the 7th and 14th day ( p < 0.05). The CIH‐induced transiently upregulation of the TASK‐1 expression in the hypoglossal nucleus could be reversed by 5‐HT 2A receptor antagonist, indicating that the modulation of the TASK‐1 expression in response to CIH involves 5‐HT and 5‐HT 2A receptors, and this CIH effect might be 5‐HT 2A receptor‐dependent.

Background Aplastic anemia (AA), a disease of bone marrow failure, is caused by CD8 + T mediated apoptosis of hematopoietic cells. However, traditional immunosuppressive therapy (IST) has severe liver and kidney toxicity and even cannot achieve the expected therapeutic effect in some patients. Purpose Our study is aimed to investigate the effect and mechanism of dioscin (DNS) for treating AA. Methods Briefly, we established and evaluated the AA mouse model, DNS and positive control drugs were used for intervention treatment. After 14 days of intervention, femoral bone marrow pathology, bone marrow mononuclear cells (BMMCs) apoptosis rate, bone marrow CD34+ cell surface Fas (CD95) expression and Fas signaling pathway key proteins were detected. Results After the establishment of the AA mouse model, the number of peripheral blood cells including granulocytes, erythrocytes, hemoglobin, platelets and reticulocytes in the AA group model was significantly decreased compared with the group control (P < 0.01). The degree of bone marrow hyperplasia in the sternum and femur is extremely low. After different drug interventions, compared with the group model, the number of peripheral blood cells in the AA mice rebounded significantly in group DNS (P < 0.01). Not only that the apoptosis rate of BM-MCs decreased (P < 0.01), meanwhile, the CD95 molecule expressed on the CD34+ bone marrow cells had a significant decline (P < 0.01), and the expression level of the key proteins of Fas signaling pathway was also significantly decreased (P < 0.01). Conclusion DNS recovered the peripheral pancytopenia and bone marrow failure in AA mice. DNS reduced the key protein of Fas signaling pathway level to inhibit apoptosis of bone marrow cells to treat AA.

Neuromuscular compensation of the genioglossus muscle can be induced by chronic intermittent hypoxia (CIH) in obstructive sleep apnea to maintain upper airway stability. Noradrenergic activation of hypoglossal nucleus plays a critical role in the central control of the genioglossus. However, it remains unknown whether norepinephrine takes part in the central regulation of the genioglossus during CIH. Adult male Wistar rats (n = 32) were studied to explore the influence of noradrenergic activation of hypoglossal nucleus on the central control of the genioglossus at different stages of CIH. The rats were divided into four groups: normal control or normoxic (NO) group, CIH group, CIH + normal saline (NS) group, and CIH + prazosin (PZ, α1-adrenergic antagonist) group. PZ (0.2 mM, 60 nl) and NS (0.9%, 60 nl) were microinjected into the hypoglossal nucleus. The responses of the genioglossus corticomotor area to transcranial magnetic stimulation (TMS) were recorded on the 1st, 7th, 14th, and 21st day of CIH. The CIH group showed significantly shorter TMS latencies on days 1, 7, and 14 (3.85 ± 0.37 vs. 4.58 ± 0.42, 3.93 ± 0.17 vs. 4.49 ± 0.55, 3.79 ± 0.38 vs. 4.39 ± 0.30 ms, P < 0.05), and higher TMS amplitudes on day 1 (2.74 ± 0.87 vs. 1.60 ± 0.52 mV, P < 0.05) of CIH than the NO group. Compared to the CIH + NS group, the CIH + PZ group showed decreased TMS responses (longer latencies and lower amplitudes) only on the 14th day of CIH (3.99 ± 0.28 vs. 4.61 ± 0.48 ms, 2.51 ± 0.67 vs. 1.18 ± 0.62 mV, P < 0.05). These results indicated that noradrenergic activation of the hypoglossal nucleus played a role in the central compensation of genioglossus through α1-adrenoceptor on the 14th day of CIH.