Neuropeptides最新文献

Physiologically relevant lactate accumulation from exercise or peripheral injection does not alter central or peripheral appetite signaling in mice 运动或外周注射造成的与生理相关的乳酸积累不会改变小鼠的中枢或外周食欲信号传导

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-09-19 DOI: 10.1016/j.npep.2024.102473

Lactate has been implicated in exercise-induced appetite suppression though little work has explored the mechanisms underpinning its role. Recent work suggests lactate accumulation via exercise and intracerebroventricular injection can alter central appetite regulating pathways, though a supraphysiological dose of lactate was administered centrally and there was no assessment of peripheral appetite markers. Therefore, we examined how physiologically relevant lactate accumulation via exercise or intraperitoneal injection altered central and peripheral appetite signaling pathways and whether the lactate dehydrogenase inhibitor oxamate could blunt any exercise effect. Forty 10-week-old C57BL/6 J male mice (n = 10/group) were assigned to either: 1) sedentary (SED + SAL; saline); 2) exercise (EX+SAL; saline); 3) exercise with oxamate (EX+OX; 750 mg‧kg⁻¹ body mass); or 4) lactate (SED + LAC; 1.0 g‧kg⁻¹ body mass). Blood, stomach, and hypothalamus samples were collected ∼2 h post-exercise/injection. Though oxamate blunted exercise-induced lactate accumulation compared to the EX+SAL condition (P = 0.044, d = 0.73), there were no differences in circulating acylated ghrelin or stomach ghrelin O-acyltransferase content between groups (P > 0.213,

η_{p}^{2}

<0.125). There were also no differences in hypothalamic content for neuropeptide Y, proopiomelanocortin, agouti-related peptide, and alpha melanocyte-stimulating hormone (P > 0.150,

η_{p}^{2}

<0.170). Exercise did increase phosphorylated-total signal transducer and activator of transcription 3 (pSTAT3) compared to EX+OX (p = 0.065, d = 1.23) but there were no differences in other markers of lactate signaling: phosphorylated-total adenosine monophosphate activated protein kinase, and protein kinase b (P > 0.121,

η_{p}^{2}

<0.160). Our results suggest that lactate accumulation due to exercise or peripheral injection does not alter central or peripheral appetite signaling when measured 2 h post-exercise/injection, though pSTAT3 was blunted with oxamate.

乳酸盐与运动引起的食欲抑制有关，但很少有研究探讨其作用机制。最近的研究表明，通过运动和脑室内注射进行乳酸盐蓄积可改变中枢食欲调节途径，但乳酸盐是超生理剂量的，而且没有对外周食欲标记物进行评估。因此，我们研究了通过运动或腹腔注射造成的生理学相关乳酸累积如何改变中枢和外周食欲信号通路，以及乳酸脱氢酶抑制剂草酸盐是否能减弱任何运动效应。40只10周大的C57BL/6 J雄性小鼠（n = 10/组）被分配到以下任一组：1）静坐（SED + SAL；生理盐水）；2）运动（EX+SAL；生理盐水）；3）含草酸盐的运动（EX+OX；750 mg‧kg-1体重）；或4）乳酸盐（SED + LAC；1.0 g‧kg-1体重）。运动/注射后 2 小时采集血液、胃和下丘脑样本。虽然与 EX+SAL 条件相比，草氨酸盐能减弱运动诱导的乳酸累积（P = 0.044，d = 0.73），但不同组间的循环酰化胃泌素或胃泌素 O-酰基转移酶含量没有差异（P > 0.213，ηp2<0.125）。下丘脑中的神经肽 Y、前黑皮素、激动相关肽和α-黑素细胞刺激素含量也没有差异（P> 0.150, ηp2<0.170）。与 EX+OX 相比，运动确实增加了磷酸化-信号转导子和转录激活子 3（pSTAT3）的总量（P = 0.065，d = 1.23），但乳酸信号转导的其他标记物：磷酸化-单磷酸腺苷激活的蛋白激酶总量和蛋白激酶 b（P > 0.121，ηp2<0.160）并无差异。我们的结果表明，运动或外周注射导致的乳酸积聚不会改变运动/注射后 2 小时的中枢或外周食欲信号传导，尽管草氨酸会减弱 pSTAT3。

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引用次数: 0

GnRH protective effects against long-term potentiation impairment induced by AANAT-siRNA GnRH对AANAT-siRNA诱导的长期延时损伤的保护作用

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-09-18 DOI: 10.1016/j.npep.2024.102474

There is an interplay between the gonadotropin-releasing hormone (GnRH) and melatoninergic systems. The key enzyme of melatonin synthesis (arylalkylamine N-acetyltransferase, AANAT), and GnRH receptors are expressed in the hippocampus. While it has been shown that hippocampal AANAT enzyme activity is necessary for proper hippocampal cognitive function, their role in long-term potentiation (LTP) induction is not fully understood. In current study, the impact of GnRH on LTP induction was investigated, while hippocampal melatonin synthesis had been inhibited. The melatonin synthesis was inhibited by AANAT-siRNA administration, and LTP was induced using in vivo field potential electrophysiological recording.

Animals were divided into 5 groups: Intact, vehicle, siRNA, GnRH and siRNA+GnRH. All animals, except intact group, experienced the stereotaxic surgery and intra-hippocampal cannulation to receive vehicle agent, AANAT siRNA (0.5 μg/hip), GnRH (1 ng/rat), and AANAT siRNA+GnRH. The recognition memory was assessed by Novel object recognition test. The field potential electrophysiology experiment was conducted by stimulating the Schaffer collateral pathway, and LTP induction was carried out through high-frequency stimulation (HFS). After recording, animals' brain was isolated and quickly frozen for further hippocampal melatonin levels measurement by LC-MS and AANAT mRNA levels by qRT-PCR.

GnRH injection in the hippocampus increased local AANAT-mRNA expression and melatonin levels. GnRH-treated animals displayed higher LTP amplitude compared to intact, vehicle and siRNA groups. While the reduction in hippocampal melatonin levels by AANAT-siRNA inhibited LTP and impaired recognition memory, the GnRH prevented these adverse effects. The data suggests that GnRH have protective effects against AANAT-siRNA-induced LTP decline. The protective mechanism at least partially, may be related to the increased expression of local AANAT-mRNA.

促性腺激素释放激素（GnRH）和褪黑激素能系统之间存在相互作用。褪黑激素合成的关键酶（芳基烷基胺 N-乙酰转移酶，AANAT）和促性腺激素释放激素受体都在海马中表达。有研究表明，海马 AANAT 酶的活性是海马正常认知功能所必需的，但它们在长期延时（LTP）诱导中的作用尚未完全明了。本研究在抑制海马褪黑激素合成的同时，研究了GnRH对LTP诱导的影响。通过AANAT-siRNA抑制褪黑激素的合成，并使用体内场电位电生理记录诱导LTP。动物被分为 5 组：动物分为 5 组：完整组、载体组、siRNA 组、GnRH 组和 siRNA+GnRH 组。除完整组外，所有动物均接受立体定向手术和海马内插管，分别接受载体、AANAT siRNA（0.5 μg/hip）、GnRH（1 ng/rat）和AANAT siRNA+GnRH。识别记忆通过新物体识别测试进行评估。场电位电生理学实验通过刺激沙弗侧路进行，LTP诱导通过高频刺激（HFS）进行。记录结束后，动物大脑被分离并快速冷冻，以进一步通过LC-MS测定海马褪黑激素水平，并通过qRT-PCR测定AANAT mRNA水平。在海马中注射 GnRH 增加了局部 AANAT mRNA 的表达和褪黑激素水平。经GnRH处理的动物的LTP振幅高于完整组、车辆组和siRNA组。AANAT-siRNA 降低了海马褪黑激素水平，抑制了 LTP 并损害了识别记忆，而 GnRH 则防止了这些不利影响。这些数据表明，GnRH对AANAT-siRNA诱导的LTP下降具有保护作用。这种保护机制至少部分可能与局部 AANAT-mRNA 表达的增加有关。

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引用次数: 0

Phosphorylated NPY1R regulates phenotypic transition of vascular smooth muscle cells, inflammatory response and macrophage infiltration to promote intracranial aneurysm progression 磷酸化的 NPY1R 可调控血管平滑肌细胞的表型转换、炎症反应和巨噬细胞浸润，从而促进颅内动脉瘤的进展

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-09-06 DOI: 10.1016/j.npep.2024.102465

Background

Rupture of intracranial aneurysm (IA) could give rise to spontaneous subarachnoid hemorrhage, leading to a high disability rate and even death. NPY1R expression was upregulated in aneurysm tissues of IA patients. However, the role and underlying mechanism of NPY1R remains unknown.

Methods

The IA model of mice was established using inducing systemic hypertension and injecting elastase. The expression of genes and proteins was detected by RT-qPCR and western blot. The number of T cells, macrophages, and neutrophils in IA mice was detected using flow cytometry and IF assay. The levels of inflammatory factors were measured using ELISA. Patho-morphology and inflammatory cells in aneurysm tissues were evaluated by HE staining. The interaction between TK and NPY1R was validated using Co-IP.

Results

NPY1R expression was greatly elevated in aneurysm tissues in IA patients and mice, which were positively related to macrophage infiltration. Besides, exogenous overexpression of NPY1R resulted in the promotion of contractile phenotype to the synthetic phenotype of vascular smooth muscle cells (VSMCs), inflammatory response and M1 macrophage polarization. In terms of the underlying mechanism, NPY1R protein could be modified by TK-mediated phosphorylation and TKI could decrease IA formation and suppresse contractile phenotype to synthetic phenotype of VSMCs, inflammatory response and M1 macrophage polarization in IA mice. Furthermore, ablating mouse macrophages abolished NPY1R overexpression-mediated promotion of IA formation and rupture in mice.

Conclusion

Phosphorylated NPY1R contributed to IA progression through promoting contractile phenotype to synthetic phenotype of VSMCs, inflammatory response and M1 macrophage polarization in IA.

背景颅内动脉瘤（IA）破裂可引起自发性蛛网膜下腔出血，导致高致残率甚至死亡。NPY1R在IA患者的动脉瘤组织中表达上调。方法通过诱导全身性高血压和注射弹性蛋白酶建立小鼠 IA 模型。通过 RT-qPCR 和 Western blot 检测基因和蛋白质的表达。流式细胞术和 IF 检测法检测了 IA 小鼠体内 T 细胞、巨噬细胞和中性粒细胞的数量。使用 ELISA 检测炎症因子的水平。动脉瘤组织的病理形态和炎性细胞通过 HE 染色法进行评估。结果NPY1R在IA患者和小鼠动脉瘤组织中的表达显著升高，与巨噬细胞浸润呈正相关。此外，外源性过表达 NPY1R 会导致血管平滑肌细胞（VSMCs）收缩表型向合成表型转变、炎症反应和 M1 巨噬细胞极化。在其潜在机制方面，NPY1R蛋白可被TK介导的磷酸化修饰，TKI可减少IA的形成，并支持IA小鼠的收缩表型向血管平滑肌细胞合成表型转变、炎症反应和M1巨噬细胞极化。此外，消融小鼠巨噬细胞可消除 NPY1R 过表达介导的促进小鼠 IA 形成和破裂的作用。

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引用次数: 0

The restraint stress-induced antinociceptive effects decreased by antagonism of both orexin receptors within the CA1 region of the hippocampus 拮抗海马 CA1 区的两种奥曲肽受体可降低束缚应激引起的抗痛觉效应

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-08-22 DOI: 10.1016/j.npep.2024.102463

Studies have indicated that stress-related symptoms can lead to hormonal and neural changes, affecting the pain threshold and nociceptive behaviors. The precise role of orexin receptors (OX1r and OX2r) in stress-induced analgesia (SIA) remains an inquiry yet to be comprehensively elucidated. The current investigation aimed to assess the impact of acute immobilization restraint stress on pain-related behavioral responses after administering antagonists targeting OX1r and OX2r in a rat model using the tail-flick test. After a period of five to seven days post-stereotaxic surgery in CA1, the baseline tail-flick latency (TFL) was recorded for each animal. Subsequently, rats were unilaterally administered varying doses of the OX1r antagonist (SB334867; 1, 3, 10, and 30 nmol), the OX2r antagonist (TCS OX2 29; 1, 3, 10, and 30 nmol), or a vehicle (0.5 μl solution containing 12% DMSO) through an implanted cannula. Following a 5-min interval, the animals were subjected to a restraint stress (RS) lasting for 3 h. The tail-flick test was conducted after the stress exposure, and the TFLs were assessed at 60-min intervals. The findings of this study revealed that RS elicits antinociceptive responses in the tail-flick test. Microinjection of OX1r and OX2r antagonists into the CA1 attenuated RS-induced analgesia during the tail-flick test. Furthermore, the results underscored the preeminent role of OX2 receptors in modulating SIA. In conclusion, the orexin system localized within the hippocampal CA1 region may, in part, contribute to the manifestation of SIA in the context of acute pain.

研究表明，压力相关症状会导致荷尔蒙和神经发生变化，影响痛阈和痛觉行为。奥曲肽受体（OX1r和OX2r）在应激诱导镇痛（SIA）中的确切作用仍有待全面阐明。目前的研究旨在评估在大鼠模型中使用针对 OX1r 和 OX2r 的拮抗剂后，急性固定束缚应激对疼痛相关行为反应的影响。大鼠在CA1区接受立体定向手术后五到七天，记录每只动物的基线弹尾潜伏期（TFL）。随后，通过植入插管给大鼠单侧注射不同剂量的 OX1r 拮抗剂（SB334867；1、3、10 和 30 nmol）、OX2r 拮抗剂（TCS OX2 29；1、3、10 和 30 nmol）或载体（0.5 μl 含有 12% DMSO 的溶液）。间隔 5 分钟后，对动物进行持续 3 小时的束缚应激（RS）。应激暴露后进行弹尾试验，每隔 60 分钟评估一次 TFL。该研究结果表明，RS能在弹尾试验中引起抗痛觉反应。向CA1显微注射OX1r和OX2r拮抗剂可减轻RS在尾叩试验中诱导的镇痛。此外，研究结果还强调了 OX2 受体在调节 SIA 中的重要作用。总之，位于海马CA1区的奥曲肽系统可能在一定程度上导致了急性疼痛背景下的SIA表现。

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引用次数: 0

Ninjinyoeito ameliorates anorexia and changes in peptide YY and ghrelin levels of cisplatin-treated mice 万年青能改善顺铂治疗小鼠的厌食症以及肽 YY 和胃泌素水平的变化。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-08-22 DOI: 10.1016/j.npep.2024.102464

We explored the effect of Ninjinyoeito (NYT) on cisplatin-induced anorexia, which reduces cancer patient survival. Both gastrointestinal motility and plasma concentrations of gastrointestinal peptides were assessed. Nine-week-old ICR female mice received intraperitoneal cisplatin injections (10 mg/kg) and daily oral NYT doses of 300 mg/kg (NYT300) or 1000 mg/kg (NYT1000). Plasma levels of gastrointestinal peptides were measured at 3 and 6 days after cisplatin injection. Gastrointestinal motility was assessed by analyzing the concentration of phenol red marker within sections of the gastrointestinal tract. Cisplatin-injected mice showed a decrease in daily food intake, but this effect was attenuated on day 5 with NYT1000 administration. Although plasma ghrelin levels were reduced on day 3 in cisplatin-treated mice, NYT1000 administration ameliorated this decrease. However, there were no differences in ghrelin levels among all groups on day 6. Levels of peptide YY (PYY) were elevated in the plasma of cisplatin-injected mice on days 3 and 6. Administration of NYT300 and NYT1000 suppressed the increase in PYY levels on day 6 but not on day 3. Gastrointestinal motility was impaired on day 6 in cisplatin-treated mice, but NYT1000 administration attenuated this effect. Our results suggest that NYT improves cisplatin-induced anorexia by suppressing alterations in ghrelin and PYY levels and by increasing gastrointestinal motility. Therefore, NYT may be a promising candidate for alleviating cisplatin-induced anorexia.

顺铂会降低癌症患者的生存率，我们探讨了万年青（NYT）对顺铂诱发的厌食症的影响。我们对胃肠道蠕动和胃肠道肽的血浆浓度进行了评估。9周大的ICR雌性小鼠腹腔注射顺铂（10毫克/千克），每天口服300毫克/千克（NYT300）或1000毫克/千克（NYT1000）剂量的NYT。顺铂注射后3天和6天测量血浆中胃肠道肽的水平。通过分析胃肠道切片中酚红标记物的浓度来评估胃肠道蠕动。顺铂注射小鼠的日摄食量有所下降，但在第5天服用NYT1000后，这种影响有所减弱。虽然顺铂治疗小鼠的血浆胃泌素水平在第3天有所下降，但服用NYT1000后这种下降趋势得到了改善。然而，在第 6 天，各组之间的胃泌素水平没有差异。顺铂注射小鼠血浆中的肽YY（PYY）水平在第3天和第6天升高。服用 NYT300 和 NYT1000 可抑制第 6 天PYY 水平的升高，但不能抑制第 3 天PYY 水平的升高。顺铂治疗小鼠的胃肠道运动在第6天受到损害，但服用NYT1000可减轻这种影响。我们的研究结果表明，NYT可通过抑制胃泌素和PYY水平的变化以及增加胃肠道蠕动来改善顺铂诱导的厌食症。因此，NYT可能是缓解顺铂诱导的厌食症的一种有希望的候选药物。

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引用次数: 0

Melittin protects against neural cell damage in rats following ischemic stroke Melittin 可防止大鼠缺血性中风后神经细胞受损

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-08-13 DOI: 10.1016/j.npep.2024.102462

Objective

In this study, we explored the neuroprotective effect of melittin (MEL) after brain ischemia using a rat model.

Methods

The rats underwent middle cerebral artery occlusion (MCAO) for 60 min and were randomly divided into the control group, saline group, and MEL group. Rats in each group were injected intraperitoneally with MEL one day before MCAO until sacrificed. Morris water maze and rotation test were used to assess locomotor function and cognitive ability. The 9.4 Tesla MRI was used to scan and assess the infarct volume of the rat brains. Immunohistochemistry was used to detect the sites of action of MEL on microglia. Western blot and ELISA were used to measure the effect of MEL on the production of pro-inflammatory cytokines. The effect of MEL on neuronal cell apoptosis was observed by flow cytometry.

Results

Compared with the saline group, MEL treatment significantly increased the density of neurons in the cerebral cortical and reduced the cerebral infarct size after MCAO (33.9 ± 8.8% vs. 15.8 ± 3.9%, P < 0.05). Meanwhile, the time for MEL-treated rats to complete the water maze task on the 11th day after MCAO was significantly shorter than that of rats in the saline group (P < 0.05). MEL treatment also prolonged the rotarod retention time on day 14 after MCAO. Immunohistochemistry analysis showed that MEL inhibited the activation of microglia and suppressed the expression of TNF-α, IL-6, and IL-1β in the brain after ischemia. MEL treatment resulted in a significant decrease in TLR4, MyD88, and NF-κB p65 levels in extracts from the ischemic cerebral cortex. Finally, MEL reduced neuronal apoptosis induced by ischemic stroke (P < 0.05).

Conclusion

MEL treatment promotes neurological function recovery after cerebral ischemia in rats. These effects are potentially mediated through anti-inflammatory and anti-apoptotic mechanisms.

方法大鼠大脑中动脉闭塞（MCAO）60分钟，随机分为对照组、生理盐水组和MEL组。各组大鼠在MCAO前一天腹腔注射MEL，直至死亡。采用莫里斯水迷宫和旋转测试评估大鼠的运动功能和认知能力。用9.4特斯拉核磁共振成像扫描和评估大鼠大脑的梗死体积。免疫组织化学用于检测MEL对小胶质细胞的作用部位。Western blot 和 ELISA 用于测量 MEL 对促炎细胞因子产生的影响。结果与生理盐水组相比，MEL能显著增加MCAO后大脑皮层神经元的密度，缩小脑梗死面积（33.9±8.8% vs. 15.8±3.9%，P <0.05）。同时，MEL治疗大鼠在MCAO后第11天完成水迷宫任务的时间明显短于生理盐水组大鼠（P < 0.05）。MEL治疗还延长了MCAO后第14天大鼠的旋转木马保持时间。免疫组化分析表明，MEL抑制了小胶质细胞的活化，并抑制了缺血后脑中TNF-α、IL-6和IL-1β的表达。MEL 处理可显著降低缺血大脑皮层提取物中 TLR4、MyD88 和 NF-κB p65 的水平。结论 MEL 治疗可促进大鼠脑缺血后神经功能的恢复。这些作用可能是通过抗炎和抗凋亡机制介导的。

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引用次数: 0

Upregulation of Xbp1 in NPY/AgRP neurons reverses diet-induced obesity and ameliorates leptin and insulin resistance 上调 NPY/AgRP 神经元中的 Xbp1 可逆转饮食引起的肥胖，并改善瘦素和胰岛素抵抗。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-08-06 DOI: 10.1016/j.npep.2024.102461

The molecular mechanisms underlying neuronal leptin and insulin resistance in obesity and diabetes are not fully understood. In this study, we show that induction of the unfolded protein response transcription factor, spliced X-box binding protein 1 (Xbp1s), in Agouti-Related Peptide (AgRP) neurons alone, is sufficient to not only protect against but also significantly reverse diet-induced obesity (DIO) as well as improve leptin and insulin sensitivity, despite activation of endoplasmic reticulum stress. We also demonstrate that constitutive expression of Xbp1s in AgRP neurons contributes to improved insulin sensitivity and glucose tolerance. Together, our results identify critical molecular mechanisms linking ER stress in arcuate AgRP neurons to acute leptin and insulin resistance as well as liver glucose metabolism in DIO and diabetes.

肥胖症和糖尿病中神经元瘦素和胰岛素抵抗的分子机制尚不完全清楚。在这项研究中，我们发现，尽管激活了内质网应激，但在阿古提相关肽（AgRP）神经元中单独诱导未折叠蛋白反应转录因子--剪接的 X-box 结合蛋白 1（Xbp1s），不仅足以防止而且还能显著逆转饮食诱导的肥胖（DIO），以及改善瘦素和胰岛素敏感性。我们还证明了 Xbp1s 在 AgRP 神经元中的组成型表达有助于改善胰岛素敏感性和葡萄糖耐受性。总之，我们的研究结果确定了将弓状AgRP神经元中的ER应激与急性瘦素和胰岛素抵抗以及DIO和糖尿病中的肝糖代谢联系起来的关键分子机制。

引用次数: 0

Expression and localization of the neuropeptide Y-Y4 receptor in the chick spleen: mRNA upregulation by high ambient temperature 神经肽Y-Y4受体在雏鸡脾脏中的表达和定位：高环境温度对mRNA的上调。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-08-05 DOI: 10.1016/j.npep.2024.102459

High ambient temperatures (HT) can increase diencephalic neuropeptide Y (NPY) expression, and central injection of NPY attenuates heat stress responses while inducing an antioxidative state in the chick spleen. However, there is a lack of knowledge about NPY receptor expression, and its regulation by HT, in the chick spleen. In the current study, male chicks were used to measure the expression of NPY receptors in the spleen and other immune organs under acute (30 vs. 40 ± 1°C for 3 h) or chronic (30 vs. 40 ± 1°C for 3 h/day for 3 days) exposure to HT and in response to central injection of NPY (47 pmol, 188 pmol, or 1 nmol). We found that NPY-Y4 receptor mRNA was expressed in the spleen, but not in other immune organs studied. Immunofluorescence staining revealed that NPY-Y4 receptors were localized in the splenic pulp. Furthermore, NPY-Y4 receptor mRNA increased in the chick spleen under both acute and chronic exposure to HT. Central NPY at two dose levels (47 and 188 pmol) and a higher dose (1 nmol) did not increase splenic NPY-Y4 receptor mRNA expression or splenic epinephrine under HT (35 ± 1°C), and significantly increased 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations under HT (40 ± 1°C). In conclusion, increased expression of NPY-Y4 receptor mRNA in the spleen under HT suggest that Y4 receptor may play physiological roles in response to HT in male chicks.

高环境温度（HT）可增加间脑神经肽 Y（NPY）的表达，中心注射 NPY 可减轻热应激反应，同时诱导雏鸡脾脏的抗氧化状态。然而，人们对雏鸡脾脏中NPY受体的表达及其受热应激的调控还缺乏了解。在本研究中，我们用雄性雏鸡测量了在急性（30 vs. 40 ± 1°C 3 h）或慢性（30 vs. 40 ± 1°C 3 h/day 3 d）高温暴露下以及在中枢注射 NPY（47 pmol、188 pmol 或 1 nmol）后脾脏和其他免疫器官中 NPY 受体的表达。我们发现，NPY-Y4 受体 mRNA 在脾脏中表达，而在所研究的其他免疫器官中没有表达。免疫荧光染色显示，NPY-Y4受体定位于脾髓。此外，在急性和慢性接触 HT 的情况下，雏鸡脾脏中的 NPY-Y4 受体 mRNA 都会增加。两种剂量水平（47 和 188 pmol）和更高剂量（1 nmol）的中枢 NPY 在 HT（35 ± 1°C）条件下不会增加脾脏 NPY-Y4 受体 mRNA 表达或脾脏肾上腺素，但在 HT（40 ± 1°C）条件下会显著增加 3-甲氧基-4-羟基苯乙二醇（MHPG）浓度。总之，HT条件下脾脏中NPY-Y4受体mRNA的表达增加表明，Y4受体可能在雄性雏鸡对HT的反应中发挥生理作用。

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引用次数: 0

Trefoil factor 1 (TFF1) reduces cerebral edema and gastric mucosal injury by regulating the EGFR/Src/FAK pathway in an intracerebral hemorrhage rat model 三叶草因子 1（TFF1）通过调节表皮生长因子受体/Src/FAK 通路减轻脑出血大鼠模型的脑水肿和胃黏膜损伤

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-08-03 DOI: 10.1016/j.npep.2024.102460

The destruction of the blood-brain barrier and damage to the gastrointestinal mucosa after intracerebral hemorrhage (ICH) are important reasons for its high disability and mortality rates. However, the exact etiology is not yet clear. In addition, there are currently no effective treatments for improving cerebral edema and gastric mucosal damage after ICH. Trefoil factor 1 (TFF1) is a secretory protein that plays a crucial role in maintaining the integrity and barrier function of the gastric mucosa, and it has been reported to have a protective effect on brain damage induced by various causes. This study utilized a rat model of ICH induced by type IV collagenase was utilized, and intervened with recombinant TFF1 protein from an external institute to investigate the protective mechanisms of TFF1 against brain edema and gastric mucosal damage after ICH. The results demonstrated that TFF1 alleviated the neurological function and gastric mucosal damage in the rat model of ICH induced by type IV collagenase. TFF1 may ensure the integrity of the blood-brain and gastric mucosal barriers by regulating the EGFR (epidermal growth factor receptor)/Src (non-receptor tyrosine kinase)/FAK (focal adhesion kinase) pathway. Clearly, the disruption of the blood-brain barrier and the destruction of the gastric mucosal barrier are key pathological features of ICH, and TFF1 can improve the progression of blood-brain barrier and gastric mucosal barrier disruption in ICH by regulating the EGFR/Src/FAK pathway. Therefore, TFF1 may be a potential target for the treatment of ICH.

脑内出血（ICH）后血脑屏障的破坏和胃肠道粘膜的损伤是其致残率和死亡率高的重要原因。然而，确切的病因尚不清楚。此外，目前还没有有效的治疗方法来改善 ICH 后的脑水肿和胃黏膜损伤。三叶草因子 1（TFF1）是一种分泌蛋白，在维持胃黏膜的完整性和屏障功能方面起着至关重要的作用，有报道称它对各种原因引起的脑损伤有保护作用。本研究利用Ⅳ型胶原酶诱导的大鼠ICH模型，并用外院的重组TFF1蛋白进行干预，研究TFF1对ICH后脑水肿和胃黏膜损伤的保护机制。结果表明，TFF1 可减轻Ⅳ型胶原酶诱导的 ICH 大鼠模型的神经功能和胃黏膜损伤。TFF1可通过调节表皮生长因子受体（EGFR）/非受体酪氨酸激酶（Src）/焦点粘附激酶（FAK）通路，确保血脑屏障和胃粘膜屏障的完整性。显然，血脑屏障的破坏和胃黏膜屏障的破坏是 ICH 的主要病理特征，而 TFF1 可通过调节表皮生长因子受体/Src/FAK 通路改善 ICH 中血脑屏障和胃黏膜屏障破坏的进展。因此，TFF1可能是治疗ICH的潜在靶点。

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引用次数: 0

The protective effects of orexin B in neuropathic pain by suppressing inflammatory response 奥曲肽 B 通过抑制炎症反应对神经病理性疼痛的保护作用

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-07-30 DOI: 10.1016/j.npep.2024.102458

Chronic pain induced by pathological insults to the sensorimotor system is a typical form of neuropathic pain (NP), and the underlying mechanism is complex. Currently, there are no successful therapeutic interventions for NP. Orexin B is a neuropeptide with a wide range of biological functions. However, the pharmacological function of orexin B in chronic neuropathic pain has been less studied. Here, we aim to examine the neuroprotective effects of orexin B in chronic constriction injury (CCI)- induced NP. Firstly, we found that orexin type 2 receptor (OX2R) but not orexin type 1 receptor (OX1R) was reduced in the spinal cord (SC) of CCI-treated rats. Mechanical withdrawal threshold and thermal withdrawal latency assays display that administration of orexin B clearly ameliorated CCI-evoked neuropathic pain dose-dependently. Notably, orexin B treatment also effectively prevented microglia activation by reducing the levels of IBA1. Additionally, orexin B was also found to suppress the inflammatory response in the SC tissue by reducing the levels of IL-6, TNF-α, iNOS, and COX-2 as well as the production of NO and PGE₂ in CCI-treated rats. Furthermore, orexin B administration attenuated oxidative stress (OS) by increasing the activity of SOD and the levels of GSH. Mechanically, orexin B prevented activation of JNK/NF-κB signaling in the SC of CCI-treated rats. Based on these findings, we conclude that orexin B might have a promising role in ameliorating CCI-evoked neuropathic pain through the inhibition of microglial activation and inflammatory response.

感觉运动系统受到病理损伤而诱发的慢性疼痛是神经病理性疼痛（NP）的一种典型形式，其潜在机制十分复杂。目前，还没有成功治疗 NP 的干预措施。Orexin B 是一种神经肽，具有广泛的生物学功能。然而，关于奥曲肽 B 在慢性神经病理性疼痛中的药理功能研究较少。在此，我们旨在研究奥曲肽 B 在慢性收缩性损伤（CCI）诱导的 NP 中的神经保护作用。首先，我们发现在经 CCI 处理的大鼠脊髓（SC）中，奥曲肽 2 型受体（OX2R）减少，而奥曲肽 1 型受体（OX1R）没有减少。机械戒断阈值和热戒断潜伏期实验表明，给予奥曲肽 B能明显改善CCI诱发的神经病理性疼痛，且呈剂量依赖性。值得注意的是，奥曲肽 B 还能通过降低 IBA1 的水平有效阻止小胶质细胞的激活。此外，研究还发现奥曲肽 B 还能抑制 SC 组织中的炎症反应，降低 CCI 治疗大鼠体内 IL-6、TNF-α、iNOS 和 COX-2 的水平以及 NO 和 PGE2 的产生。此外，奥曲肽 B 还能提高 SOD 的活性和 GSH 的水平，从而减轻氧化应激（OS）。从机理上讲，奥曲肽 B 可阻止 JNK/NF-κB 信号在 CCI 治疗大鼠 SC 中的激活。基于这些发现，我们认为奥曲肽 B 可通过抑制小胶质细胞活化和炎症反应来改善 CCI 诱发的神经病理性疼痛。

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