Distribution of transient receptor potential vanilloid-1 channels in gastrointestinal tract of patients with morbid obesity

BACKGROUND Transient receptor potential vanilloid-1(TRPV1),a nonselective cation channel,is activated by capsaicin,a pungent ingredient of hot pepper.Previous studies have suggested a link between obesity and capsaicin-associated pathways,and activation of TRPV1 may provide an alternative approach for obesity treatment.However,data on the TRPV1 distribution in human gastric mucosa are limited,and the degree of TRPV1 distribution in the gastric and duodenal mucosal cells of obese people in comparison with normal-weight individuals is unknown.AIM To clarify gastric and duodenal mucosal expression of TRPV1 in humans and compare TRPV1 expression in obese and healthy individuals.METHODS Forty-six patients with a body mass index(BMI)of>40 kg/m^(2) and 20 patients with a BMI between 18-25 kg/m^(2) were included.Simultaneous biopsies from the fundus,antrum,and duodenum tissues were obtained from subjects between the ages of 18 and 65 who underwent esophagogastroduodenoscopy.Age,sex,history of alcohol and cigarette consumption,and past medical history regarding chronic diseases and medications were accessed from patient charts and were analyzed accordingly.Evaluation with anti-TRPV1 antibody was performed separately according to cell types in the fundus,antrum,and duodenum tissues using an immunoreactivity score.Data were analyzed using SPSS 17.0.RESULTS TRPV1 expression was higher in the stomach than in the duodenum and was predominantly found in parietal and chief cells of the fundus and mucous and foveolar cells of the antrum.Unlike foveolar cells in the antrum,TRPV1 was relatively low in foveolar cells in the fundus(4.92±0.49 vs 0.48±0.16,P<0.01,Mann-Whitney U test).Additionally,the mucous cells in the duodenum also had low levels of TRPV1 compared to mucous cells in the antrum(1.33±0.31 vs 2.95±0.46,P<0.01,Mann-Whitney U test).TRPV1 expression levels of different cell types in the fundus,antrum,and duodenum tissues of the morbidly obese group were similar to those of the control group.Staining with TRPV1 in fundus chief cells and antrum and duodenum mucous cells was higher in patients aged≥45 years than in patients<45 years(3.03±0.42,4.37±0.76,2.28±0.55 vs 1.9±0.46,1.58±0.44,0.37±0.18,P=0.03,P<0.01,P<0.01,respectively,Mann-Whitney U test).The mean staining levels of TRPV1 in duodenal mucous cells in patients with diabetes and hypertension were higher than those in patients without diabetes and hypertension(diabetes:2.11±0.67 vs 1.02±0.34,P=0.04;hypertension:2.42±0.75 vs 1.02±0.33,P<0.01 Mann-Whitney U test).CONCLUSION The expression of TRPV1 is unchanged in the gastroduodenal mucosa of morbidly obese patients demonstrating that drugs targeting TRPV1 may be effective in these patients.

Transient receptor potential vanilloid 4-dependent calcium influx and ATP release in mouse and rat gastric epithelia

AIM: To explore the expression of transient receptor potential vanilloid 4(TRPV4) and its physiological meaning in mouse and rat gastric epithelia. METHODS: RT-PCR and immunochemistry were used to detect TRPV4 m RNA and protein expression in mouse stomach and a rat normal gastric epithelial cell line(RGE1-01), while Ca2+-imaging and electrophysiology were used to evaluate TRPV4 channel activity. ATP release was measured by a luciferin-luciferase assay. Gastric emptying was also compared between WT and TRPV4 knockout mice. RESULTS: TRPV4 m RNA and protein were detected in mouse tissues and RGE1-01 cells. A TRPV4-specific agonist(GSK1016790A) increased intracellular Ca2+ concentrations and/or evoked TRPV4-like current activities in WT mouse gastric epithelial cells andRGE1-01 cells, but not TRPV4 KO cells. GSK1016790 A or mechanical stimuli induced ATP release from RGE1-01 cells while TRPV4 knockout mice displayed delayed gastric emptying in vivo. CONCLUSION: TRPV4 is expressed in mouse and rat gastric epithelium and contributes to ATP release and gastric emptying.

瞬时感受器电位通道vanilloid 4在机械牵张人脑微血管内皮细胞中对内皮型一氧化氮合酶的作用

目的:筛选人脑微血管内皮细胞(human brain microvascular endothelial cells,HBMEC)中瞬时感受器电位(transient receptor potential,TRP)通道亚型,检测该通道亚型在机械牵张刺激中对内皮型一氧化氮合酶(endothelial nitric oxide synthase,e NOS)蛋白表达的影响及探讨相关机制。方法:荧光定量RT-PCR(q RT-PCR)、Western印迹及细胞免疫荧光筛选HBMEC上TRP通道亚型。根据筛选的TRP通道亚型将细胞分组,应用多功能小型生物撞击机给予机械牵张刺激;流式细胞仪检测细胞牵张前后胞内Ca2+荧光强度变化;Western印迹检测e NOS蛋白表达情况。结果:q RT-PCR结果表明:TRPV4及TRPC1的m RNA相对表达量较多;细胞免疫荧光及Western印迹显示TRPV4通道蛋白表达;流式细胞仪检测结果显示,特异性TRPV4通道抑制组较单纯牵张组Ca2+相对浓度低(P<0.001),较未牵张组(P=0.072)、非特异性TRP通道抑制组(P=0.308)无明显差异。Western印迹检测结果显示:TRPV4通道抑制组和内皮型一氧化氮合酶抑制组e NOS蛋白表达水平较单纯牵张组明显降低(P<0.05),较未牵张组无明显差异(P>0.05)。结论:TRPV4在HBMEC上有表达,机械牵张将其激活后,可以引起e NOS蛋白表达增多,其机制可能与胞外Ca2+的内流有关。

Increased gene and protein expressions of the transient receptor potential vanilloid receptor 4 following sustained pure mechanical pressure on rat dorsal root ganglion neurons

Dorsal root ganglion(DRG) neurons from newborn Wistar rats cultured in vitro were pressurized with 20,40,80 or 120 mm Hg compressive loadings(1 mm Hg = 0.133 kPa) for 12,24,48 or 72 hours,respectively.The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide test showed that pressures less than 80 mm Hg had no obvious impact on the activity of DRG neurons.The protein expression levels of transient receptor potential vanilloid receptor 4(TRPV4),transient receptor potential vanilloid receptor 1,transient receptor potential channel of melastatin type 8,and transient receptor potential subtype ankyrin 1 were assessed by western blot analysis.The mRNA expression of TRPV4 was assessed by real-time PCR.The results showed that sustained mechanical compression up-regulated TRPV4 mRNA and protein expression in the rat DRG neurons,in a time-dependent fashion.Similar changes were not found in the protein expression of transient receptor potential vanilloid receptor 1,transient receptor potential channel of melastatin type 8,and transient receptor potential subtype ankyrin 1.Images of cells using a laser scanning confocal microscope showed that the sustained mechanical pressure increased the number of responsive DRG neurons and was synergistic on the enhanced Ca2+ responses to the TRPV4 phorbol ester agonist 4α-phorbol 12,13-didecanoate and hypotonic solutions.These findings demonstrate that sustained mechanical compressive loading in vitro increases the expression of TRPV4 mRNA and protein in DRG neurons and sensitizes TRPV4 Ca2+ signals.Mechanical compression does not impact other ion channels in the transient receptor potential family.

TRPV4在眼病理生理功能中的研究进展

瞬时受体电位香草醛受体4(TRPV4)是一种非选择性阳离子通道,负责感知细胞肿胀、温度、机械牵张、剪切应力和渗透压的变化,通过调节跨膜钙信号进而影响基因表达、细胞形态和细胞骨架等构建。TRPV4在全身广泛表达。在眼内,TRPV4在角膜、晶状体、睫状体、小梁网和视网膜等组织均有功能性表达。本文就TRPV4在眼内各个组织中的表达及生理病理功能方面进行阐述。随着TRPV4在眼部病理生理功能中的深入研究,TRPV4在角膜损伤修复、青光眼及视网膜血管生成方面可能成为潜在的新兴药物靶点,但仍需进一步的深入研究。

Overexpression of TRPV1 activates autophagy in human lens epithelial cells under hyperosmotic stress through Ca^(2+)-dependent AMPK/mTOR pathway

●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,300,400,500,or 600 mOsm for 6,12,18,24h in vitro.Polymerase chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein expression.The transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux.Scanning electron microscopy was used to detect the existence of autolysosome.Short interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related pathway.Flow cytometry was employed to test the apoptosis and intracellular Ca^(2+)level.Mitochondrial membrane potential was measured by JC-1 staining.The cell counting kit-8 assay was used to calculate the cellular viability.The wound healing assay was used to evaluate the wound closure rate.GraphPad 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in LECs.Beclin 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression decreased.Transient Ca^(2+)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early stage.Based on this evidence,autophagy activation through the Ca^(2+)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress.Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased.Inhibition of autophagy by ATG7 knockdown had similar results.TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress.●CONCLUSION:A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.

Serotonin receptor 2B induces visceral hyperalgesia in rat model and patients with diarrhea-predominant irritable bowel syndrome

BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.

含有TRPV1受体拮抗剂的修护霜对敏感性皮肤的改善作用

目的:评价含有TRPV1受体拮抗剂的修护霜对敏感性皮肤的改善作用及安全性。方法:采用半脸对照及使用前后自身对照研究,受试者在第一次随访根据随机号将修护霜涂抹于单侧面部,使用本品后进行即刻时间点TI敏感程度评估(30s,1 min、10 min)。随后研究期间全面部涂抹修护霜每天2次,共28天。分别在使用前(TO)、使用后48 h(T2)、使用后28d(T3)进行面部乳酸刺痛实验、生理指标检测及皮肤敏感状态主观评分。由皮肤科医生,眼科医生及耳鼻喉科医生分别在使用前和使用后10 min,48 h及28d对皮肤和眼部鼻部黏膜耐受性进行评估。结果:共收集39例受试者。受试者单侧面部涂抹修护霜10min,与未用修护霜侧相比,敏感评估量表各维度评分下降,具有统计学意义(P{<}0.001),受试者的皮肤刺激症状迅速改善。在使用修护霜30 s,1 min、10 min,48 h以及28 d后,各项敏感评估评分均较使用前下降,具有统计学意义(P{<}0.001)。使用修护霜后28天,乳酸刺痛实验评分和经表皮失水率,分别为1.46±1.52和14.91±3.90g/h·m^(2),较使用前(3.50±1.63,17.82±5.34 g/h.m^(2))降低。受试区角质层含水量(62.90±10.83)较使用前(53.91±16.07)水平增加(P{<}0.001),差异均具有统计学意义(P{<}0.01);红斑指数,pH值变化无统计学差异。研究期间未观察到与修护霜使用相关的皮肤、眼部和鼻部的任何刺激性反应及其他不良反应。结论:含有TRPV1受体拮抗剂的修护霜可快速缓解敏感性皮肤的多种不适症状并可以修复皮肤屏障,耐受性良好。

靶向瞬时受体电位香草酸亚型1离子通道的Nplus-RhTx多肽抑制剂理性设计及功能验证

目的:获得靶向瞬时受体电位香草酸亚型1(TRPV1)通道的多肽抑制剂。方法:基于已有的靶向TRPV1通道的多肽激动剂红头蜈蚣毒素(RhTx)进行理性设计,在其氨基末端增加带正电荷的氨基酸,并在细胞上使用膜片钳电生理验证设计的多肽对TRPV1通道的抑制作用。结果:理性设计了8条Nplus-RhTx多肽,在膜片钳电生理记录中发现其中4条可以抑制TRPV1的辣椒素激活,4条Nplus-RhTx多肽的半数有效抑制浓度分别为(188.3±4.7)、(193.6±18.0)、(282.8±11.9)和(299.5±6.4)µmol/L。结论:通过对RhTx多肽的氨基端进行理性设计改变其性质,可获得靶向TRPV1的多肽抑制剂。

β-细辛醚通过抑制TRPV4的表达缓解谷氨酸诱导的Ca^(2+)超载

谷氨酸处理会导致Ca^(2+)超载,瞬时受体电位香草素受体4(transient receptor potential vanilloid 4,TRPV4)在其中的作用及可能机制尚不清楚。β-细辛醚能快速透过血脑屏障,对兴奋性毒性具有较强的神经保护作用。文章以高分化的PC12细胞为研究对象,探究β-细辛醚(15、30、60μmol/L)预处理4 h,40 mmol/L谷氨酸处理实时记录对PC12细胞Ca^(2+)浓度的影响,采用钙成像技术检测Ca^(2+)浓度的变化;采用实时荧光定量聚合酶链式反应(polymerase chain reaction,PCR)、Western Blot及免疫荧光技术检测TRPV4的mRNA和蛋白的表达;采用Lipofectiamine 2000脂质体实验转染TRPV4-siRNA和pEX-3-TRPV4,观察沉默和过表达TRPV4对谷氨酸引起Ca^(2+)超载的影响。结果表明:与正常对照组相比,谷氨酸处理5 min可诱导Ca^(2+)超载,显著提高TRPV4的mRNA和蛋白的表达;与模型组相比,β-细辛醚能够剂量依赖性地降低谷氨酸诱导的Ca^(2+)超载和TRPV4的表达;沉默TRPV4抑制细胞Ca^(2+)超载;过表达TRPV4则部分逆转β-细辛醚抑制谷氨酸诱导的Ca^(2+)超载。该研究证明,谷氨酸处理PC12细胞5 min通过上调TRPV4的表达诱导Ca^(2+)超载,β-细辛醚作为TRPV4的拮抗剂,是一种潜在的抑制兴奋性毒性的药物。

TRPV1通道在感染性疾病中的研究进展

瞬时感受器电位香草酸受体1(TRPV1)是瞬时感受电位家族成员中的一种非选择性阳离子通道,主要表达在感觉神经元上。TRPV1在体内分布广泛,生物作用复杂。近年来,研究发现通过激活或抑制TRPV1可以调控炎性因子、疼痛信号传导、体温和神经元敏感性等,参与感染性疾病的产生,但目前还未用于临床。本文参阅国内外相关文献,以TRPV1为靶点,对TRPV1在感染性疾病中的生理作用及其调控机制的研究进展作一综述,为感染性疾病的防治提供新思路。

Vanilloid受体激动剂吴茱萸碱的辣椒素样减肥作用

吴茱萸碱是吴茱萸果实中的主要生物碱,具有辣椒素样vanilloid受体激动活性,且没有明显的味道,而辣椒素浓烈的辛辣味限制了其在减肥方面的应用。作者用雄性 C3H小鼠和SD大鼠研究了吴茱萸碱和吴茱萸果实提取物预防肥胖的作用。禁食24 h后的小鼠分为2组,1组喂饲普通饲料(对照组),另1组喂饲含0.03％吴茱萸碱的饲料,12天后2组动物禁食1天,尔后处死,立即切除并称量肾周及附睾的脂肪垫。在另一实验中,大鼠分为2组。

The relationship between the expression of transient receptor potential vanilloid 1 and the airway remodeling in elderly patients with chronic obstructive pulmonary disease

Objective To investigate the relationship between the expression of trannsient receptor potential vanilloid(TRPV1)and the severity of airway remodeling in elderly patients with chronic obstructive pulmonary disease(COPD).Methods According to airflow obstruction severity,totally 100 cases of elderly patients with

Role of transient receptor potential vanilloid subetype 1 in the increase of thermal pain threshold by moxibustion

OBTECTIVE:To explore the role of transient receptor potential vaniiloid subetype 1(TRPV1) in the increase of the thermal pain threshold by moxibustion.METHODS:Forty Kunming mice(20 ± 2) g were randomized into control group,capsaicin group,capsazepine group,moxibustion group and moxibustion + capsazepine(MC) group with 8 mice in each,and 16 C57BL/6 wild-type mice(18 ± 2) g were randomized into wild-type(WT) control group and WT moxibustion group with 8 mice in each,and 14 TRPV1 knockout mice(18 ± 2) g were randomized into knockout(KO) control group and KO moxibustion group with 7 in each.Each mouse in the capsaicin group was subcutaneously injected with the amount of 0.1 mL/10 g into L5 and L6 spinal cords;each mouse in the capsazepine group was intraperitoneally injected with the amount of0.1 mL/10 g.Similarly,each mouse in the moxibustion group was given a suspended moxibustion with specially-made moxa-stick for 20 min on L5 and L6 spinal cords.Each mouse in MC group was intraperitoneally injected with the amount of 0.1 mL/10 g first,then after 15 min was given a suspended moxibustion for 20 min on L5 and L6 spinal cords.Each mouse in WT moxibustion group and KO moxibustion group was given a suspended moxibustion with specially-made moxa-stick for 20 min on L5 and L6 spinal cords.The control group,WT control group and KO control group were of no treatment in any way.After all treatments were completed,the digital-display measurement instrument for thermal pain was used to measure the threshold of thermal pain in each group respectively.RESULTS:Compared with the control group,the thresholds of thermal pain in the moxibustion group and MC group were significantly increased(P <0.01);no significant changes in the thresholds in the capsaicin group and the capsazepine group(P > 0.05);compared with moxibustion group,he threshold of thermal in MC group was obviously decreased(P < 0.01).Compared with WT control group,the threshold of thermal pain in WT moxibustion group was significantly increased(P <0.01);compared with KO control group,no changes in the threshold in KO moxibustion group(P > 0.05).CONCLUSION:TRPV1 participated in the process of increasing the threshold of thermal pain by stimulating L5 and L6 of mice spinal cord with burning mosa-stick.

口腔鳞状细胞癌中TRPV2的表达及其临床病理意义

目的探究口腔鳞状细胞癌(OSCC)中TRPV2的表达及其临床病理意义。方法免疫组化及Western blot检测TRPV2在OSCC中的表达水平,Pearsonχ^(2)检验分析TRPV2表达与OSCC患者临床病理的关系,Log-rank检验分析TRPV2对生存期的影响。生物信息学方法探索TRPV2的潜在生物学功能,及免疫组化验证TRPV2与巨噬细胞浸润水平的关系。结果免疫组化及Western blot证实TRPV2在OSCC中高表达(P<0.05),且TRPV2高表达与OSCC患者T分期、肿瘤组织学分级、预后不佳具有相关性(P<0.05)。生物信息学方法发现TRPV2参与PI3K/AKT等通路及调控免疫细胞浸润水平,免疫组化验证TRPV2高表达与巨噬细胞浸润水平呈正相关(R=0.562,P<0.001)。结论TRPV2在OSCC中高表达且与预后不佳相关,可通过PI3K/AKT等通路及调控巨噬细胞免疫浸润水平参与OSCC的发生及发展。

基于PGE2/PKC/TRPV1信号通路研究热敏灸对膝骨性关节炎兔镇痛效应机制

目的观察热敏灸对膝骨性关节炎(KOA)兔血清PGE2、背根神经节PKC、穴区皮肤TRPV1的影响,探讨其治疗KOA的作用机制。方法36只雄性普通级新西兰兔随机分为空白组(6只)、假手术组(6只)、造模组(24只)。采用木瓜蛋白酶溶液注射膝关节腔法造模15d,假手术组关节腔内注射等量的0.9%NaCl溶液。造模成功后,造模组随机分成模型组(6只),艾灸组(18只),艾灸组艾灸“犊鼻”穴,每日1次,每次40 min,共7 d,根据兔艾灸过程中温度变化分为热敏灸组(10只)和非热敏灸组(7只),空白组、假手术组、模型组不予干预措施。干预结束后,肉眼、光镜下观察膝关节滑膜形态学变化;ELISA法检测血清PGE2表达;Real-time PCR法检测各组兔背根神经节PKC mRNA、穴区皮肤TRPV1 mRNA的含量。结果(1)干预后模型组兔膝关节腔内有大量积液,滑膜增生肥厚,伴有血管增生及大量炎症细胞成团聚集;热敏灸及非热敏灸组关节腔内积液减少,滑膜异常增生改善。(2)与空白组比较,模型组血清PGE2含量明显上升(P<0.01);与模型组比较,热敏灸组、非热敏灸组血清PGE2含量下降,差异有统计学意义(均P<0.01);与非热敏灸组比较,热敏灸组血清PGE2含量下降,差异有统计学意义(P<0.05)。(3)与空白组比较,模型组背根神经节PKC mRNA、穴区皮肤TRPV1 mRNA含量升高,差异有统计学意义(均P<0.01);与模型组比较,热敏灸及非热敏灸组PKC、TRPV1 mRNA表达下降,差异有统计学意义(均P<0.01);与非热敏灸组比较,热敏灸组PKC、TRPV1 mRNA表达下降,差异有统计学意义(P<0.05)。结论热敏灸可抑制PGE2、PKC、TRPV1的高表达,从而抑制痛觉过敏,减轻KOA滑膜炎性反应,缓解关节损害,这可能是热敏灸治疗KOA的效应机制之一。

Effect of exogenous hydrogen sulfide in the nucleus tractus solitarius on gastric motility in rats

BACKGROUND Hydrogen sulfide(H2S)is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems.It exerts its effects through multiple signaling pathways,impacting various physiological activities.The nucleus tractus solitarius(NTS),a vital nucleus involved in visceral sensation,was investigated in this study to understand the role of H2S in regulating gastric function in rats.AIM To examine whether H2S affects the nuclear factor kappa-B(NF-κB)and transient receptor potential vanilloid 1 pathways and the neurokinin 1(NK1)receptor in the NTS.METHODS Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase(CBS)and c-Fos co-expressed positive neurons in the NTS during rat stress.Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus.Changes in gastric motility were observed before and after injecting different doses of NaHS(4 nmol and 8 nmol),physiological saline,Capsazepine(4 nmol)+NaHS(4 nmol),pyrrolidine dithiocarbamate(PDTC,4 nmol)+NaHS(4 nmol),and L703606(4 nmol)+NaHS(4 nmol).RESULTS We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group.Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats(P<0.01).However,injection of saline,first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1(TRPV1)antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes(P>0.05).CONCLUSION NTS contains neurons co-expressing CBS and c-Fos,and the injection of NaHS into the NTS can suppress gastric motility in rats.This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.

TRPV4在眼科疾病中的研究进展

瞬态电位受体香草醛4(TRPV4)是一组存在于细胞膜上的非选择性阳离子通道。它们是调节细胞功能和信号通路的感觉信号的重要介质。TRPV4在眼部各种组织中广泛表达,可参与多种生理功能,包括渗透压调节、Ca^(2+)稳态、凋亡和自噬,在正常生理功能以及不同病理中起重要作用。最近研究发现TRPV4与角膜上皮损伤、青光眼、年龄相关性白内障、糖尿病视网膜病变、早产儿视网膜病变、视网膜脱离等疾病紧密联系,调控着相关眼科疾病的发生和发展过程。本文就TRPV4通路在眼科疾病中的研究进展做简要综述,为临床眼病治疗提供思路。

变应性鼻炎的鼻痒发病机制初探

鼻痒作为变应性鼻炎(AR)的主要症状之一严重困扰患者的生活,但目前仍没有完全根治鼻痒的治疗方法,因此,明确AR鼻痒发病机制尤为重要。近年来,AR的神经免疫机制引起许多学者的关注,其中瞬时感受器电位香草酸受体1型(TRPV1)是神经免疫机制的核心要素,在AR鼻痒的发病机制中发挥着重要的桥梁作用。该文综合近年来瘙痒生理病理学机制的研究进展,同时聚焦AR鼻痒的神经传导通路,并从与AR鼻痒有关的免疫细胞(肥大细胞和嗜碱性粒细胞)、介质及信号受体、痒感传入神经(三叉神经),以及基于TRPV1离子通道剖析AR鼻痒的神经-免疫联动调控网络机制等进行综述,期望为AR鼻痒的临床治疗提供系统的理论依据。