Melatonin Receptors Agonistic Activities of Phenols from Gastrodia elata

Gastrodia elata is a famous traditional Chinese herb with medicinal and edible application.In this study,three new polybenzyls,gastropolybenzylols G-I(1-3)were isolated from the EtOAc extract of G.elata.Their structures were identified by extensive spectroscopic analyses involving HRESIMS,UV,IR,1D and 2D NMR.Compound 1 showed agonistic effects on MT1 and MT_(2) receptors with agonistic rates of 55.91±4.84%and 165.13±5.65%at the concentration of 0.5 mM,respectively,and an EC_(50) value of 76.24μM on MT_(2) receptor.

Hepatoprotective actions of melatonin:Possible mediation by melatonin receptors

Melatonin,the hormone of darkness and messenger of the photoperiod,is also well known to exhibit strong direct and indirect antioxidant properties. Melatonin has previously been demonstrated to be a powerful organ protective substance in numerous models of injury; these beneficial effects have been attributed to the hormone's intense radical scavenging capacity. The present report reviews the hepatoprotective potential of the pineal hormone in various models of oxidative stress in vivo,and summarizes the extensive literature showing that melatonin may be a suitable experimental substance to reduce liver damage after sepsis,hemorrhagic shock,ischemia/reperfusion,and in numerous models of toxic liver injury. Melatonin's influence on hepatic antioxidant enzymes and other potentially relevant pathways,such as nitric oxide signaling,hepatic cytokine and heat shock protein expression,are evaluated. Based on recent literature demonstrating the functional relevance of melatonin receptor activation for hepatic organ protection,this article finally suggests that melatonin receptors could mediate the hepatoprotective actions of melatonin therapy.

Distribution of melatonin receptor in human fetal brain

Objective:To studythedistributionof2kindsof melatoninreceptorsubtypes(mt1andMT2)in humanfetal brain.Methods:Thefetalbraintissueswereslicedandthedistributionof melatoninreceptorsinhumanfetalbrainwere detectedusingimmunohistochemistryandin situ hybridization.Results:Melatoninreceptormt1existedinthecerebellum andhypothalamus,melatoninreceptorMT2existsinhypothalamus,occipitalandmedulla.Conclusion:Two kindsof melatoninreceptors,mt1andMT2existinthemembraneandcytosolof braincells,indicatingthathumanfetalbrainis a targetorganof melatonin.

Effects of Kaixin Powder(开心散)on Melatonin Receptor Expression and ^(125)I-Mel Binding Affinity in A Rat Model of Depression

Objective： To explore the effects of Kaixin Powder （开心散, KXP） on melatonin receptor （MR） expression and 1261-Mel binding affinity in a depression rat model. Methods： Seventy-two male Wistar rats were divided into six groups： a blank control group, model group, ramelteon group, KXP high-dosage group （HKXP）, medium-dosage group （MKXP） and low-dosage group （LKXP）. To establish the depression model, all groups except the blank control group were singly housed and exposed to chronic unpredictable mild stress. Weight gain, sucrose consumption and the open-field test were used to evaluate induction of depression. KXP at 260, 130 and 65 mg/（kg·d） was also respectively administered to the rats in the HKXP, MKXP and LKXP groups for 21 days. Ramelteon [0.83 mg/（kg·d）] was given to the positive drug control group. An equivalent volume of physiological saline was given to the blank and model groups. The liquid chip method was used to measure the concentration of plasma melatonin （MT）. Mell a （MT1） and Mellb （MT2） expression levels were determined by Western blotting. In addition, a radioactive ligand-binding assay was used to analyze the specific binding properties and dynamic characteristics between MR and 125I-Mel. Results： The results of weight gain, sucrose consumption and the open-field test showed that our model successfully produced depressive symptoms and depressive-like behavior. The concentration of plasma MT in the model group decreased significantly at night but increased in the MKXP group （P〈0.05）. The HKXP group showed significantly increased expression of MT1 （P〈0.05）; however, the expression of MT2 in all groups exhibited no significant differences （P〉0.05）. The maximum binding capacity （Bmax） for specific binding between MR and 125I-Mel in the MKXP group was significantly higher than that in the model group （P〈0.05）, but no significant differences were found in the equilibrium dissociation constant （Kd） of each group （P〉0.05）. Conclusions： KXP may have a similar effect as ramelteon. KXP improved depressive-like behavior by increasing the concentration of plasma MT and MT1 expression, thereby increasing three Bmax of MR tO achieve the desired antidepressant effect.

Changes of melatonin and its receptors in synchronizing turbot(Scophthalmus maximus)seasonal reproduction and maturation rhythm

In most fish,reproduction is seasonal or periodic under the suitable conditions.In turbot(Scophthalmus maximus)farms,one of the most economically important marine flatfish species,changes in daylength could cause changes in the spawning time.In this study,to characterize the regulation of reproductive physiology following light signals,three melatonin receptors(Mtnr)investigated in turbot were named sm Mtnr1,sm Mtnr2,and sm Mtnr1 c.Distinct expression profiles demonstrated that Mtnr m RNAs were concentrated in the brain(as detected in the hypothalamus(Hy)and mesencephalon(Me)),gonad and eye.The most abundant Mtnr1 and Mtnr2 m RNA expression levels were detected in the central nervous system at the beginning of the breeding season,suggesting that Mtnr1 and Mtnr2 may play vital roles in the regulation of turbot gonadal development.In addition,the melatonin profiles gradually increased and reached to the highest level at the spawning stage,indicating that melatonin is a potent hormone in the regulation of fish oocyte growth and maturation.The results of this study suggested that melatonin is the primary factor that transduces the light signal and regulates the physiological functions of turbot seasonal reproduction.Moreover,the results of this study may establish a foundation for further research seeking to identify fish melatonin receptors involved in the gonadal development and gamete maturation.

Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus

Melatonin receptor 1B(MT2,encoded by the MTNR1B gene),a high-affinity receptor for melatonin,is associated with glucose homeostasis including glucose uptake and transport.The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus(GDM);however,the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood.This article aims to investigate the relationship between rs10830963 variants and GDM development,as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts.TaqMan-MGB(minor groove binder)probe quantitative realtime polymerase chain reaction(qPCR)assays were used for rs10930963 genotyping.MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence,western blot,and qPCR.The relationship between MT2 and glucose transporters(GLUTs)or peroxisome proliferator-activated receptorγ(PPARγ)was established by western blot,and glucose consumption of trophoblasts was measured by a glucose assay kit.The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women(P<0.05).The fasting,1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers(P<0.05).Besides,the protein and messenger RNA(mRNA)expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women(P<0.05).Melatonin could stimulate glucose uptake and GLUT4 and PPARγprotein expression in trophoblasts,which could be attenuated by MT2 receptor knockdown.In conclusion,the rs10830963 variant was associated with an increased risk of GDM.The MT2 receptor is essential for melatonin to raise glucose uptake and transport,which may be mediated by PPARγ.

Melatonin Enhances Object Recognition Memory through Melatonin MT1 and MT2 Receptor-Mediated and Non-Receptor-Mediated Mechanisms in Male Mice

Melatonin (MEL) has been reported to have acute enhancing effects on some aspects of cognition. Recently, we revealed that N1-acetyl-5-methoxyquinuramine (AMK), a brain metabolite of MEL, is much more potent than MEL in converting short-term memory (STM) to long-term memory (LTM) with a single administration immediately after the acquisition trial of the novel object recognition (NOR) task. These data suggest that the memory-enhancing effects of MEL may be mediated by mechanisms independent of the activation of MEL MT1 and MT2 receptors. In the present study, we examined the contribution of MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms to the acute memory-enhancing effects of MEL using NOR task. Mice were administered with either MEL, AMK, or a highly selective MT1/MT2 receptor agonist ramelteon (RAM) immediately after the acquisition trial and the effects of varying doses of these drugs on both STM and LTM performance were compared. We found that both AMK and RAM were more potent than MEL in both facilitating STM and promoting LTM formation. We also found that pretreatment with luzindole, a MT1/MT2 receptor antagonist, markedly suppressed only the effects of RAM. These results suggest that acutely administered MEL enhances NOR memory through both MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms.

Seasonal variation of melatonin secretion across various segments of the gastrointestinal tract in rats

Objective:To investigate whether melatonin(MT)secretion in different parts of the gastrointestinal tract(GIT)exhibits seasonal variations and its correlation with immune regulation.Methods: Sixty Sprague-Dawley rats were divided into control and model groups,and the pineal gland was removed in the model group.Stomach,jejunum,ileum,and colon tissues were obtained during the spring equinox,summer solstice,beginning of autumn,autumn equinox,and winter solstice.The levels of MT,MT receptors(MR),arylalkylamine N-acetyltransferase(AANAT),hydroxyindole-O-methyltransferase(HIOMT),interleukin-2(IL-2),and interleukin-10(IL-10)in the GIT were measured using enzyme-linked immunosorbent assay.Results: Except for the stomach,the jejunum,ileum,and the colon showed seasonal tendencies in MT secretion.In the control group,MT secretion in the jejunum and ileum was the highest in the long summer,and colonic MT secretion was the highest in winter.In the model group,MT levels in the colon were highest in the summer.The seasonal rhythms of the MR,AANAT,HIOMT,IL-2,and IL-10 in the colon were roughly similar to those of MT,and changed accordingly after pinealectomy.Conclusions: Gastrointestinal MT secretion is related to seasonal changes,and MT secretion in each intestinal segment is influenced by different seasons.The biological effects of MT in the gut are inextricably linked to the mediation of MR,and a hormone-receptor linkage exists between MT and MR.The effect of seasonal changes on the gastrointestinal immune system may be mediated through the regulation of seasonal secretion of MT.

UFLC‑PDA‑MS/MS Profling of Seven Uncaria Species Integrated with Melatonin/5‑Hydroxytryptamine Receptors Agonistic Assay

Uncariae Ramulus Cum Uncis(Gou-Teng),the dried hook-bearing stems of several Uncaria plants(Rubiaceae),is a wellknown herbal medicine in China.The clinical application of Gou-Teng is bewildered for the morphological and chemical similarity between diferent species.In order to discern their chemical and biological diference,an ultra-fast liquid chromatography equipped with ion trap time-of-fight mass spectrometry(UFLC-IT/TOF-MS)combining with melatonin(MT1 and MT2)and 5-hydroxytryptamine(5-HT1A and 5-HT2C)receptors agonistic assay in vitro was conducted on seven Uncaria species.As a result,57 compounds including 35 indole alkaloids,ten favonoids,fve triterpenoids,fve chlorogenic analogues,and two other compounds were characterized based on their MS/MS patterns and UV absorptions.Specifcally,cadambine-type and corynanthein-type alkaloids were exclusively present in U.rhynchophylla and U.scandens,whereas corynoxine-type alkaloids were commonly detected in all the seven Uncaria plants.Three Uncaria species,U.rhynchophylla,U.macrophylla,and U.yunnanensis showed obviously agnostic activity on four neurotransmitter receptors(MT1,MT2,5-HT1A,and 5-HT_(2C)).This frst-time UFLCMS-IT-TOF analyses integrated with biological assay on seven Uncaria plants will provide scientifc viewpoints for the clinical application of Gou-Teng.

急性呼吸窘迫综合征患儿血清Melatonin、MIP-1α与NLRP3炎症小体和预后的关系分析

目的探讨急性呼吸窘迫综合征(ARDS)患儿血清褪黑素(Melatonin)、巨噬细胞炎性蛋白-1α(MIP-1α)与核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体和预后的关系。方法选取2021年1月至2023年1月该院收治的ARDS患儿140例纳入ARDS组,另选取同期100例体检健康儿童纳入对照组。根据入院28 d临床结局将ARDS患儿分为死亡组29例和存活组111例。采用酶联免疫吸附试验检测血清Melatonin、MIP-1α、白细胞介素(IL)-1β、IL-18水平,实时荧光定量PCR检测NLRP3 mRNA、半胱氨酸蛋白酶-1(Caspase-1)mRNA水平。采用Pearson相关分析ARDS患儿血清Melatonin、MIP-1α水平与NLRP3炎症小体相关指标(NLRP3 mRNA、Caspase-1 mRNA、IL-1β、IL-18)的相关性。采用多因素Cox回归分析影响ARDS患儿预后的因素。根据ARDS患儿血清Melatonin、MIP-1α水平均值分为高/低血清Melatonin、MIP-1α组,Kaplan-Meier法绘制高/低血清Melatonin、MIP-1α水平ARDS患儿生存曲线。采用受试者工作特征(ROC)曲线分析血清Melatonin、MIP-1α对ARDS患儿死亡的预测价值。结果与对照组比较,ARDS组血清Melatonin水平降低,血清MIP-1α、IL-1β、IL-18和外周血单核细胞NLRP3 mRNA、Caspase-1 mRNA水平升高(P<0.05)。Pearson相关分析显示,ARDS患儿血清Melatonin水平与NLRP3 mRNA、Caspase-1 mRNA、IL-1β、IL-18均呈负相关(P<0.05),MIP-1α水平与NLRP3 mRNA、Caspase-1 mRNA、IL-1β、IL-18均呈正相关(P<0.05)。多因素Cox回归分析显示,急性生理学和慢性健康状况评价Ⅱ评分、NLRP3 mRNA、Caspase-1 mRNA、IL-1β、IL-18、MIP-1α为影响ARDS患儿预后的独立危险因素,Melatonin为独立保护因素(P<0.05)。Kaplan-Meier生存曲线分析显示,高血清Melatonin组28 d生存率高于低血清Melatonin组(P<0.05),高血清MIP-1α组28 d生存率低于低血清MIP-1α组(P<0.05)。ROC曲线分析显示,血清Melatonin、MIP-1α联合预测ARDS患儿死亡的曲线下面积为0.881(95%CI 0.816~0.930),大于血清Melatonin、MIP-1α单独预测的0.785(95%CI 0.708~0.850)、0.778(95%CI 0.700~0.844)。结论ARDS患儿血清Melatonin水平降低、MIP-1α水平升高,与NLRP3炎症小体和预后密切相关,联合检测血清Melatonin、MIP-1α水平对ARDS患儿预后具有较高的预测价值。

2-Iodomelatonin上调NRF2表达对缺血性脑损伤神经保护作用

目的探讨褪黑激素受体1(MT1)激动剂2-Iodomelatonin通过上调核因子E2相关因子2(NRF2)对大脑中动脉栓塞小鼠的神经保护作用。方法采用大脑中动脉栓塞(MCAO)法制备小鼠缺血性脑损伤体内模型,给予2-Iodomelatonin及NRF2抑制剂(Nrf2-IN-1)干预。采用三苯基氯化四氮唑(TTC)染色法检测小鼠大脑的梗死体积,Western Blot法检测缺血损伤后大脑皮质半暗带NRF2表达水平,改良神经功能缺损程度评分(mNSS)评估2-Iodomelatonin和Nrf2-IN-1干预对小鼠缺血性脑损伤亚急性期运动功能的影响。结果TTC染色结果显示,2-Iodomelatonin干预可以显著降低缺血性脑损伤小鼠的大脑梗死体积(F=7.79,q=5.06,P<0.05)。Western Blot结果显示,2-Iodomelatonin干预可上调小鼠皮质梗死半暗带NRF2的表达水平(F=10.56,q=3.99,P<0.05)。mNSS评分结果显示,2-Iodomelatonin干预可以显著改善缺血性脑损伤第14天的运动功能损伤(F=6.12,q=4.79,P<0.05),该效应可被Nrf2-IN-1逆转(q=3.60,P<0.05)。结论2-Iodomelatonin干预可以通过上调NRF2降低缺血性脑损伤小鼠的大脑梗死体积并改善14 d时的运动功能损伤。

Pharmacological advantages of melatonin in immunosenescence by improving activity of T lymphocytes

Melatonin plays a critical role in regulating photoperiodic signals and has recently been shown to decrease immunosenescence with age. In this study, we examined whether melatonin activates T lymphocytes as major adaptive immune cells in in vitro and in vivo models. Splenocytes, CD4＋, and naive CD4 T lymphocytes were isolated from the spleen of BALB/c mice and the cell population patterns and mRNA profiles associated with T cell activation （CD28 and p21） and the melatonin receptor （MT1A and MT1B） were assessed. The T cell activation- related proteins Ki67 and Bcl2 were also evaluated to confirm the relationship between gene and protein levels. Our data clearly revealed that CD28, p21, MT 1 A, and MT 1B mRNA were highly expressed in the presence of melatonin. Co-culture of CD4＋ T lymphocyte and peritoneal macrophage 7 days after melatonin administration to young and aged mice significantly increased APRIL mRNA, suggesting induction or maintenance of T lymphocyte responses. We also found that the intracellular amount of Ki67 and Bcl2 proteins were significantly upregulated in aged CD4＋ T lymphocytes, suggesting enhancing T cell proliferation and ling-term maintenance of memory T cells. Taken together, we conclude that melatonin supplementation may enhance immunity in aged individuals by upregulating immunosenescence indices in association with T lymphocytes and may be an attractive pharmacological candidate for aged and immunocompromised individuals.

Role of melatonin on diabetes-related metabolic disorders

Melatonin is a circulating hormone that is mainly re- leased from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms, its levels being high during the night and low during the day. Interestingly, insulin levels are also adapted to day/night changes through melatonin-dependent synchronization. This regulation may be explained by the inhibiting action of melatonin on insulin release, which is transmitted through both the pertussis-toxin-sensitive membrane receptors MT1 and MT2 and the second messengers 3',5' -cyclic adenosine monophosphate, 3',5'-cyclic guanosine monophosphate and inositol 1,4,5-trisphosphate. Melatonin may influence diabetes and associated metabolic disturbances not only by regulating insulin secretion, but also by providing protection against reactive oxygen species, since pancreatic β-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. On the other hand, in several genetic association studies, single nucleotide polymorphysms of the human MT2 receptor have been described as being causally linked to an elevated risk of developing type 2 diabetes. This suggests that these individuals maybe more sensitive to the actions of melatonin, thereby leading to impaired insulin secretion. Therefore, block- ing the melatonin-induced inhibition of insulin secretion may be a novel therapeutic avenue for type 2 diabetes.

Distribution,function and physiological role of melatonin in the lower gut

Melatonin is a hormone with endocrine, paracrine andautocrine actions. It is involved in the regulation of multiple functions, including the control of the gastroin-testinal (GI) system under physiological and pathophys-iological conditions. Since the gut contains at least 400times more melatonin than the pineal gland, a reviewof the functional importance of melatonin in the gutseems useful, especially in the context of recent clinicaltrials. Melatonin exerts its physiological effects throughspecific membrane receptors, named melatonin-1 re-ceptor (MT1), MT2 and MT3. These receptors can befound in the gut and their involvement in the regulationof GI motility, inflammation and pain has been reportedin numerous basic and clinical studies. Stable levels ofmelatonin in the lower gut that are unchanged follow-ing a pinealectomy suggest local synthesis and, further more, implicate physiological importance of endogenous melatonin in the GI tract. Presently, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. These human studies include patients with lower GI diseases, especially patients with irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. In this review, we summarize the presently available information on melatonin effects in the lower gut and discuss available in vitro and in vivo data. We furthermore aim to evaluate whether melatonin may be useful in future treatment of symptoms or diseases involving the lower gut.

Circadian dysrhythmia-linked diabetes mellitus: Examining melatonin's roles in prophylaxis and management

Diabetes mellitus is a chronic, life-threatening metabolic disorder that occurs worldwide. Despite an increase in the knowledge of the risk factors that are associated with diabetes mellitus, its worldwide prevalence has continued to rise; thus, necessitating more research into its aetiology. Recent researches are beginning to link a dysregulation of the circadian rhythm to impairment of intermediary metabolism; with evidences that circadian rhythm dysfunction might play an important role in the aetiology, course or prognosis of some cases of diabetes mellitus. These evidences thereby suggest possible relationships between the circadian rhythm regulator melatonin, and diabetes mellitus. In this review, we discuss the roles of the circadian rhythm in the regulation of the metabolism of carbohydrates and other macronutrients; with emphasis on the importance of melatonin and the impacts of its deficiency on car-bohydrate homeostasis. Also, the possibility of using melatonin and its analogs for the "prophylaxis" or management of diabetes mellitus is also considered.

Pinealectomy affects the diurnal variations in 2－［^（125）I］ iodomelatonin binding sites in chicken bursa of Fabricius

The diurnal variations of 2-[125I]iodomelatonin binding densities and affinities in the bursa of pinealectomized and shamoperated chickens were studied.The pineals of 2-day-old chickens were removed,and 7 chickens from each group were decapitated at 6 wee

The molecular mechanisms of the analgesic action of melatonin

Objective To analyse the potential involvement of the opioid receptor gene expression in the mechanisms of the analgesic action of melatonin.Methods A trauma-pain model was established in Wistar rats by combining right-hind limb amputation with 50 ℃ tail-flick test.Antinociception was determined by tail-flick latency to hot waster at 50 ℃.RT-PCR was used to observe the the expression of the M1OR and KOR gene.Results Melatonin produced the antinociceptive effect in dose-dependent manner after i.p or i.c.v.administration.Injected i.c.v.to rats,naloxone(10 μg)obviously antagonized the antinociceptive effect induced by i.p.melatonin.The expression of the M1OR gene in the rat hypothalamus and the KOR gene in the hippocampus was both significantly reduced at day 3 after injury,which was parallel to the reduction of the rat pain thresholds.However,the expression of the M1OR gene in the hippocampus and the KOR gene in the hypothalamus was not changed.Treatment of trauma-pain rats with melatonin(30-120 mg·kg-1)i.p.administrated induced the up-regulation of M1OR mRNA in the hypothalamus and the KOR mRNA in the hippocampus in a concentration-dependent manner.Conclusions The present observations suggest that Melatonin-induced antinociceptive effect may partially contribute to the up-regulation of M1OR mRNA level in the hypothalamus and the KOR mRNA level in the hippocampus.

The Regulatory Role and Mechanism of Circadian Rhythm in Hemoglobin Co-cultured Neurovascular Unit

Objective Intracranial hemorrhage(ICH),the second most common subtype of stroke,exacerbates the disruption of the blood-brain barrier(BBB),leading to vasogenic edema,plasma protein extravasation,and infiltration of neurotoxic substances.The clearance capacity of the brain plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery after hemorrhage.This study aimed to investigate the effect of circadian rhythms on BBB function,neuronal damage,and clearance capabilities.Methods The transwell model and hemoglobin were co-cultured to simulate the BBB environment after ICH.After intervention with different light groups,neuronal apoptosis was determined,glial phagocytosis was analyzed,the expression of endogenous clearing-related proteins aquaporin 4(AQP4)and low-density lipoprotein receptor-related protein 1(LRP1)was detected by western blotting and immunofluorescence dual standard method,and the expression of the tight junction protein occludin and melatonin receptor 1A(MTNR1A)was quantitatively analyzed.Results Circadian rhythms play a key role in maintaining the integrity of the BBB,reducing oxidative stress-induced neuronal damage,and improving microglial phagocytosis.Meanwhile,the expression of occludin and MTNR1A in neurovascular unit(NVU)co-cultured with hemoglobin improved the expression of AQP4 and LRP1,the key proteins in the NVU's endogenous brain clearance system.Conclusion Circadian rhythm(alternating black and white light)protects the NVU BBB function after ICH,promotes the expression of proteins related to the clearance of the hematoma,provides new evidence for the clinical treatment of patients recovering from ICH,and improves the circadian rhythm to promote brain metabolism and hematoma clearance.

褪黑素通过NF-κB/NLRP3信号抑制子宫内膜异位症的进展机制研究

目的:探讨褪黑素(MEL)对子宫内膜异位症(EMT)进展的抑制作用,以及其对核转录因子κB(NF-κB)/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)信号的调控机制。方法:通过自体子宫内膜皮下种植法构建EMT大鼠。动物实验模型分假手术组(Sham组,大鼠在造模过程中仅进行子宫片段剪取)和实验处理4组,分别为:模型组(EMT组,大鼠进行自体子宫内膜皮下种植)、褪黑素组(EMT+MEL组,以50 mg/kg的MEL灌胃处理)、EMT+NF-κB信号通路激活剂佛波酯(PMA)组(EMT+PMA组,以5 mg/kg的PMA腹腔注射)、EMT+MEL+PMA组(以50 mg/kg的MEL灌胃处理和5 mg/kg的PMA腹腔注射)。检测各组大鼠子宫内膜异位的质量、血清和腹腔液中肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的含量;免疫组化、免疫荧光检测各组样本中髓过氧化物酶(MPO)、血管内皮生长因子(VEGF)的表达;Western blot实验检测各组样本中NF-κB/NLRP3信号通路相关蛋白的表达。结果:与Sham组相比,实验处理4组大鼠中动情周期紊乱的比例、异位子宫内膜的质量、血清以及腹腔液中TNF-α和IL-6的含量、MPO和VEGF的表达及NF-κB/NLRP3信号通路相关蛋白的表达均明显升高,差异均有统计学意义(P<0.05)。与EMT组相比,EMT+MEL组和EMT+MEL+PAM组以上各项指标明显下降,而EMT+PAM组各项指标明显升高;与EMT+MEL组相比,EMT+MEL+PAM组、EMT+PAM组以上各项指标明显升高,以上差异均有统计学意义(P<0.05)。结论:MEL能明显抑制EMT中的炎症反应,抑制EMT的进展,这可能通过抑制NF-κB/NLRP3信号的激活实现的。

ACAT1和MTNR1B基因多态性与非酒精性脂肪性肝病易感性的关系

目的本研究拟探讨乙酰辅酶A乙酰转移酶1(ACAT1)和褪黑激素受体1B(MTNR1B)基因多态性与非酒精性脂肪性肝病(NAFLD)疾病易感性的关系。方法本研究共纳入2020年12月—2022年6月就诊于青岛市市立医院的健康体检者164例、NAFLD患者228例。采用PCR及测序的方法对ACAT1 rs1044925、rs1157651和MTNR1B rs10830963基因多态性进行基因分型,并采集空腹静脉血进行生化检测。符合正态分布的计量资料两组间比较采用成组t检验;非正态分布的计量资料两组间比较采用Mann-Whitney U非参数检验;计数资料两组间比较采用χ2检验。结果ACAT1 rs1044925、rs1157651和MTNR1B rs10830963基因型分布在NAFLD及健康对照组间无统计学差异(P值均>0.05),ACAT1 rs1044925 AA基因型携带者的LDL水平明显高于C等位基因携带者(Z=−2.08,P=0.04),MTNR1B rs10830963 G等位基因携带者空腹血糖水平明显高于CC基因型携带者(Z=−3.01,P<0.01)。结论ACAT1 rs1044925、rs1157651和MTNR1B rs10830963多态性与NAFLD易感性无明显相关,ACAT1 rs1044925和MTNR1B rs10830963位点分别与LDL和空腹血糖水平有关。