目的探讨功能性消化不良(functional dyspepsia,FD)患者血浆中神经肽S受体1(neuropeptide S receptor 1,NPSR1)、降钙素基因相关肽(calcitonin gene related peptide,CGRP)及白介素-6(interleukin-6,IL-6)的表达水平及其临床意义。方法...目的探讨功能性消化不良(functional dyspepsia,FD)患者血浆中神经肽S受体1(neuropeptide S receptor 1,NPSR1)、降钙素基因相关肽(calcitonin gene related peptide,CGRP)及白介素-6(interleukin-6,IL-6)的表达水平及其临床意义。方法选取2012年4月至2015年10月就诊于本院的143例FD患者纳入FD组,其中,上腹痛综合征(epigastric pain syndrome,EPS)70例(EPS组),餐后不适综合征(postprandial distress syndrome,PDS)73例(PDS组)。选取同期于本院体检的健康者80例纳入对照组,采用酶联免疫吸附测定(ELISA)检测所有研究对象血浆中NPSR1、CGRP及IL-6的表达水平,并进行统计学分析。结果 FD组患者最主要的临床症状为消化不良或胀气(82.52%),其次为嗳气(79.72%)、疲乏(76.22%)及腹痛(75.52%)。FD组患者血浆中NPSR1、CGRP、IL-6的表达水平分别为(170.25±16.40)、(117.43±15.58)、(92.75±6.80)pg/ml,对照组分别为(207.10±14.42)、(172.55±8.90)、(65.60±7.35)pg/ml,两组比较差异具有显著性(P<0.05)。PDS组患者血浆中NPSR1、CGRP、IL-6水平分别为(158.55±17.43)、(106.72±14.65)、(88.42±7.15)pg/ml,EPS组分别为(182.00±16.66)、(128.54±16.64)、(97.50±6.75)pg/ml,两组比较差异显著(P<0.05)。结论FD患者血浆中NPSR1、CGRP表达水平下降,而IL-6表达水平升高,提示NPSR1、CGRP及IL-6的表达水平与FD的发生密切相关。展开更多
Ghrelin is a neuropeptide that has various physiological functions and has been demonstrated to be neuroprotective in a number of neurological disease models.However,the underlying mechanisms of ghrelin in Parkinson’...Ghrelin is a neuropeptide that has various physiological functions and has been demonstrated to be neuroprotective in a number of neurological disease models.However,the underlying mechanisms of ghrelin in Parkinson’s disease remain largely unexplored.The current study aimed to study the effects of ghrelin in a 6-hydroxydopamine(6-OHDA)-induced Parkinson’s disease model and evaluate the potential underlying mechanisms.In the present study,we treated an SH-SY5 Y cell model with 6-OHDA,and observed that pretreatment with different concentrations of ghrelin(1,10,and 100 nM)for 30 minutes relieved the neurotoxic effects of 6-OHDA,as revealed by Cell Counting Kit-8 and Annexin V/propidium iodide(PI)apoptosis assays.Reverse transcription quantitative polymerase chain reaction and western blot assay results demonstrated that 6-OHDA treatment upregulatedα-synuclein and lincRNA-p21 and downregulated TG-interacting factor 1(TGIF1),which was predicted as a potential transcription regulator of the gene encodingα-synuclein(SNCA).Ghrelin pretreatment was able to reverse the trends caused by 6-OHDA.The Annexin V/PI apoptosis assay results revealed that inhibiting eitherα-synuclein or lincRNA-p21 expression with small interfering RNA(siRNA)relieved 6-OHDA-induced cell apoptosis.Furthermore,inhibiting lincRNA-p21 also partially upregulated TGIF1.By retrieving information from a bioinformatics database and performing both double luciferase and RNA immunoprecipitation assays,we found that lincRNA-p21 and TGIF1 were able to form a double-stranded RNA-binding protein Staufen homolog 1(STAU1)binding site and further activate the STAU1-mediated mRNA decay pathway.In addition,TGIF1 was able to transcriptionally regulateα-synuclein expression by binding to the promoter of SNCA.The Annexin V/PI apoptosis assay results showed that either knockdown of TGIF1 or overexpression of lincRNA-p21 notably abolished the neuroprotective effects of ghrelin against 6-OHDA-induced neurotoxicity.Collectively,these findings suggest that ghrelin exerts neuroprotective effects against 6-OHDA-induced neurotoxicity via the lincRNA-p21/TGIF1/α-synuclein pathway.展开更多
Objective To explore the regulating effect of moxibustion on the enteric nervous system of rats with Crohn＇s disease. Methods Ten SD rats were selected randomly from 40 rats as normal control（group A）, and the othe...Objective To explore the regulating effect of moxibustion on the enteric nervous system of rats with Crohn＇s disease. Methods Ten SD rats were selected randomly from 40 rats as normal control（group A）, and the other 30 rats were established into Crohn＇s disease rat models by adopting clysis method with TNBS. On the basis of modeling successfully, the model rats were randomly divided into model group（group B）, herbs-partitioned moxibustion group（group C） and mild moxibustion group（group D） with 8 rats in each group（4 rats were dead during modeling. After modeling, 2 rats were selected from group A, and 2 rats were selected from models for determination,at last, 8 rats were included in each group）. In group C and group D, herbs-partitioned moxibustion or mild moxibustion was applied on ＂Tiānshū（天枢 ST 25）＂ bilaterally, and the rats in group A and group B were fixed as in treatment groups. HE stain was conducted, and morphological observation was performed on the colonic tissue of rats; the expression levels of proteins of S-100, SP, NPY and their receptors were observed by adopting immunohistochemical method. Results Compared with group A, the expression levels of proteins of S-100, SP and its receptor NK1R, NPY and its receptors NPY1R and NPY2R in the intestinal tract of rats in model groups increased obviously, and the differences were statistically significant.（P_（S-100）0.01, P_（SP）0.05, P_（NK1R）0.01, P_（NPY）0.05, P_（NPY1R）0.05, P_（NPY2R）0.01）, after treatment with drug-paste interposed moxibustion and mild moxibustion, the levels reduced significantly（P_（S-100）0.05, P_（SP）0.05, P_（NK1R）0.01, P_（NPY）0.05, P_（NPY1R）0.05, P_（NPY2R）0.01）. Conclusion Moxibustion treatment may regulate the expression levels of proteins of S-100, SP, NK1R, NPY, NPY1R and NPY2R through warm stimulation, alleviate inflammatory response of colonic tissue, and repair impaired colonic mucosa, thus achieving the goal of treating Crohn＇s disease.展开更多
目的探讨神经肽S受体1(neuropeptide S receptor 1,NPSR1)和消极应对在慢性心理应激反应中的中介效应。方法采用分层随机整群抽样方法在广西南丹县抽取366名当地普通居民对其进行生活事件量表(the life eventss cale,LES)、简化症状自...目的探讨神经肽S受体1(neuropeptide S receptor 1,NPSR1)和消极应对在慢性心理应激反应中的中介效应。方法采用分层随机整群抽样方法在广西南丹县抽取366名当地普通居民对其进行生活事件量表(the life eventss cale,LES)、简化症状自评量表、简易应对方式量表(the simplified coping style questionnaire,SCSQ)的测试,采用酶联免疫吸附测定检测调查对象血浆中的NPSR1表达水平,利用SPSS21.0和AMOS21.0统计学软件进行统计分析。结果慢性心理应激水平为(25.24±29.26)分,消极应对(14.84±4.35)分,躯体因子、焦虑因子、抑郁因子、敌对因子分别为(1.58±0.58)分,(1.43±0.56)分,(1.44±0.55)分,(1.23±0.37)分。生活事件总分与消极应对、躯体因子、焦虑因子、抑郁因子、敌对因子呈正相关(r=0.23~0.46,P<0.05),与NPSR1水平呈负相关(r=-0.26,P<0.05);NPSR1水平与躯体因子、焦虑因子、抑郁因子、敌对因子呈负相关(r=-0.18^-0.61,P<0.05);消极应对与躯体因子、焦虑因子、抑郁因子、敌对因子呈正相关(r=0.12~0.27,P<0.05)。在结构方程的中介模型中,拟合指标均达到理想值(χ2=0.349,GFI=0.993,AGFI=0.979,RMSEA=0.018,CFI=0.998),神经肽S受体1与消极应对对慢性心理应激引起的情绪反应的中介效应均显著(P<0.05),效应值分别为-0.08,0.05。根据Bootstrapping法检验中介模型的结果显示:Bias-Corrected的标准化总效应、标准化间接效应、标准化直接效应的95%CI均不与0相交。结论NPSR1和消极应对在由应激引起的应激性情绪反应中起到双重中介效应。展开更多
基金supported by the National Natural Science Foundation of China,No.81901417(to XH)the Natural Science Foundation Doctoral Research Initiation Plan of Liaoning Province of China,No.2019-BS-287(to XH)the China Postdoctoral Science Foundation,No.2019M661173(to XH)。
文摘Ghrelin is a neuropeptide that has various physiological functions and has been demonstrated to be neuroprotective in a number of neurological disease models.However,the underlying mechanisms of ghrelin in Parkinson’s disease remain largely unexplored.The current study aimed to study the effects of ghrelin in a 6-hydroxydopamine(6-OHDA)-induced Parkinson’s disease model and evaluate the potential underlying mechanisms.In the present study,we treated an SH-SY5 Y cell model with 6-OHDA,and observed that pretreatment with different concentrations of ghrelin(1,10,and 100 nM)for 30 minutes relieved the neurotoxic effects of 6-OHDA,as revealed by Cell Counting Kit-8 and Annexin V/propidium iodide(PI)apoptosis assays.Reverse transcription quantitative polymerase chain reaction and western blot assay results demonstrated that 6-OHDA treatment upregulatedα-synuclein and lincRNA-p21 and downregulated TG-interacting factor 1(TGIF1),which was predicted as a potential transcription regulator of the gene encodingα-synuclein(SNCA).Ghrelin pretreatment was able to reverse the trends caused by 6-OHDA.The Annexin V/PI apoptosis assay results revealed that inhibiting eitherα-synuclein or lincRNA-p21 expression with small interfering RNA(siRNA)relieved 6-OHDA-induced cell apoptosis.Furthermore,inhibiting lincRNA-p21 also partially upregulated TGIF1.By retrieving information from a bioinformatics database and performing both double luciferase and RNA immunoprecipitation assays,we found that lincRNA-p21 and TGIF1 were able to form a double-stranded RNA-binding protein Staufen homolog 1(STAU1)binding site and further activate the STAU1-mediated mRNA decay pathway.In addition,TGIF1 was able to transcriptionally regulateα-synuclein expression by binding to the promoter of SNCA.The Annexin V/PI apoptosis assay results showed that either knockdown of TGIF1 or overexpression of lincRNA-p21 notably abolished the neuroprotective effects of ghrelin against 6-OHDA-induced neurotoxicity.Collectively,these findings suggest that ghrelin exerts neuroprotective effects against 6-OHDA-induced neurotoxicity via the lincRNA-p21/TGIF1/α-synuclein pathway.
基金Supported by:Youth Scientific Research Project of Shanghai Municipal Commission of Health and Family Planning:2013Q042National Key Basic Research Development Program(973 Program):2015CB554500+2 种基金Support Plan of New Century Excellent Talents of Ministry of Education:NCET-13-0907National Natural Science Foundation:81574079Shanghai Municipal Youth Science and Technology Venus Project:16QA1403400
文摘Objective To explore the regulating effect of moxibustion on the enteric nervous system of rats with Crohn＇s disease. Methods Ten SD rats were selected randomly from 40 rats as normal control（group A）, and the other 30 rats were established into Crohn＇s disease rat models by adopting clysis method with TNBS. On the basis of modeling successfully, the model rats were randomly divided into model group（group B）, herbs-partitioned moxibustion group（group C） and mild moxibustion group（group D） with 8 rats in each group（4 rats were dead during modeling. After modeling, 2 rats were selected from group A, and 2 rats were selected from models for determination,at last, 8 rats were included in each group）. In group C and group D, herbs-partitioned moxibustion or mild moxibustion was applied on ＂Tiānshū（天枢 ST 25）＂ bilaterally, and the rats in group A and group B were fixed as in treatment groups. HE stain was conducted, and morphological observation was performed on the colonic tissue of rats; the expression levels of proteins of S-100, SP, NPY and their receptors were observed by adopting immunohistochemical method. Results Compared with group A, the expression levels of proteins of S-100, SP and its receptor NK1R, NPY and its receptors NPY1R and NPY2R in the intestinal tract of rats in model groups increased obviously, and the differences were statistically significant.（P_（S-100）0.01, P_（SP）0.05, P_（NK1R）0.01, P_（NPY）0.05, P_（NPY1R）0.05, P_（NPY2R）0.01）, after treatment with drug-paste interposed moxibustion and mild moxibustion, the levels reduced significantly（P_（S-100）0.05, P_（SP）0.05, P_（NK1R）0.01, P_（NPY）0.05, P_（NPY1R）0.05, P_（NPY2R）0.01）. Conclusion Moxibustion treatment may regulate the expression levels of proteins of S-100, SP, NK1R, NPY, NPY1R and NPY2R through warm stimulation, alleviate inflammatory response of colonic tissue, and repair impaired colonic mucosa, thus achieving the goal of treating Crohn＇s disease.
