OBJECTIVE:To observe the influence of different moxibustion durations on hypothalamic pro-opiomelanocortin(POMC)and prodynorphin(PDYN)mRNA expressions and plasmaβ-endorphin(β-EP)content in rheumatoid arthritis(RA)ra...OBJECTIVE:To observe the influence of different moxibustion durations on hypothalamic pro-opiomelanocortin(POMC)and prodynorphin(PDYN)mRNA expressions and plasmaβ-endorphin(β-EP)content in rheumatoid arthritis(RA)rats,to understand the mechanism of moxibustion analgesia and its dose-effect relationship.METHODS:Twelve male Wistar rats were randomly selected from 48 male Wistar rats as a normal control group.The RA model was created by raising rats in a windy(blowing with electric fan),cold(6℃±2℃),and wet(80%-90%humidity)environment for 20 days,12 h each day.This was followed byinjectionofFreund'scompleteadjuvant(0.15 mL)into the ankle.Then,rats were randomly divided into a model group,moxibustion groupⅠ,and moxibustion groupⅡ,with 12 rats in each group.In moxibustion groupsⅠandⅡ,moxibustion was given at Shenshu(BL 23)and Zusanli(ST 36)for 20and 40 min,respectively,once daily for 15 days.Hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content were determined.RESULTS:Compared with the normal group,the pressure pain threshold decreased,while the hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content increased in the moxibustion groups(P<0.01).Compared with the model group,the pressure pain threshold,hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content in the moxibustion groups increased significantly(P<0.01).Compared the moxibustion groupⅠ,the pain threshold,hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content in moxibustion groupⅡsignificantly increased(P<0.01).CONCLUSION:Moxibustion has an analgesic effect and increases hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content inRArats.TheanalgesiceffectinmoxibustiongroupⅡisbetterthanthatinmoxibustiongroupⅠ.展开更多
Objective:To explore the central neurobiological mechanisms of pleasure effect on rats with neuralgia treated by tuina manipulations of An-pressing and Rou-kneading Huantiao (GB 30).Methods:A total of 64 male Sprague-...Objective:To explore the central neurobiological mechanisms of pleasure effect on rats with neuralgia treated by tuina manipulations of An-pressing and Rou-kneading Huantiao (GB 30).Methods:A total of 64 male Sprague-Dawley (SD) rats were used in this study.Eighteen rats were randomly selected as a normal group,and the other 46 rats were used to duplicate the chronic constriction injury (CCI) model.Ten rats failed in modeling and 36 rats succeeded.These 36 rats were then randomly divided into a model group and a tuina group,with 18 rats in each group.The rats in the normal group and the model group did not receive any interventions,while those in the tuina group received An-pressing and Rou-kneading Huantiao (GB 30),1 min for each time,once a day,3 weeks in total.Heating tests were evaluated to observe the change of pain-sensitivity score before intervention,1 week after intervention,2 weeks after intervention,and 3 weeks after intervention.After 1 week of intervention,2 weeks of intervention,and 3 weeks of intervention,6 rats were randomly selected from each group respectively for brain extraction.The change of Nissl's body and β-endorphin in the accumbens nucleus as well as amygdaloid nucleus of pleasure circuits,and pro-opiomelanocortin (POMC) in the arcuate nucleus were analyzed by methods of histochemistry and molecular biology.Results:After modeling,the pain-sensitivity scores of the tuina group and the model group were statistically different from the score of the normal group (both P<0.05).After An-pressing and Rou-kneading Huantiao (GB 30) for one week,the pain-sensitivity score of the tuina group had statistical difference compared with that of the model group (P<0.05).At each different time point:the amounts of Nissl's body in accumbens nucleus and amygdaloid nucleus of the tuina group were significantly more than those of the model group (all P<0.01).Besides,the numbers of β-endorphin immunoreactive cells in the accumbens nucleus and amygdaloid nucleus of the rats in the tuina group were significant展开更多
Fragmented data suggest that bisphenol AF(BPAF),a chemical widely used in a variety of products,might have potential impacts on the hypothalamus.Here,we employed male neonatal mice following maternal exposure to explo...Fragmented data suggest that bisphenol AF(BPAF),a chemical widely used in a variety of products,might have potential impacts on the hypothalamus.Here,we employed male neonatal mice following maternal exposure to explore the effects of low-dose BPAF on hypothalamic development by RNA-sequencing.We found that maternal exposure to approximately 50μg/(kg·day)BPAF from postanal day(PND)0 to PND 15 altered the hypothalamic transcriptome,primarily involving the pathways and genes associated with extracellular matrix(ECM)and intercellular adhesion,neuroendocrine regulation,and neurological processes.Further RNA analysis confirmed the changes in the expression levels of concerned genes.Importantly,we further revealed that low-dose BPAF posed a stimulatory impact on pro-opiomelanocortin(POMC)neurons in the arcuate nucleus of the hypothalamus and induced the browning of inguinal white adipose tissue.All findings indicate that developmental exposure to low-dose BPAF could interfere with hypothalamic development and thereby lead to alterations in the metabolism.Interestingly,5000μg/(kg·day)BPAF caused slighter,non-significant or even inverse alterations than the low dose of 50μg/(kg·day),displaying a dose-independent effect.Further observations suggest that the the dose-independent effects of BPAF might be associated with oxidative stress and inflammatory responses caused by the high dose.Overall,our study highlights a risk of low-dose BPAF to human neuroendocrine regulation and metabolism.展开更多
Thyroid hormone excess secondary to global type 3 deiodinase(DIO3)deficiency leads to increased locomotor activity and reduced adiposity,but also to concurrent alterations in parameters of the leptin-melanocortin syst...Thyroid hormone excess secondary to global type 3 deiodinase(DIO3)deficiency leads to increased locomotor activity and reduced adiposity,but also to concurrent alterations in parameters of the leptin-melanocortin system that would predict obesity.To distinguish the underlying contributions to the energy balance phenotype of Dlo3 deficiency,we generated mice with thyroid hormone excess targeted to pro-opiomelanocortin(POMC)-expressing cells via cell-specific DIO3 inactivation.These mice exhibit a male-specific phenotype of reduced hypothalamic Pomc expression,hyperphagia,and increased activity in brown adipose tissue,with adiposity and serum levels of leptin and thyroid hormones remained normal.These male mice also manifest a marked and widespread hypothalamic reduction in the expression of bone morphogenetic receptor 1a(BMPR1A),which has been shown to cause similar phenotypes when inactivated in PoMC-expressing cells.Our results indicate that developmental overexposure to thyroid hormone in PoMC-expressing cells programs energy balance mechanisms in a sexually dimorphic manner by suppressing adult hypothalamic BMPR1A expression.展开更多
基金Supported by 973 Program:the Research of Law and Principle of Moxibustion(No.2009CB522905)
文摘OBJECTIVE:To observe the influence of different moxibustion durations on hypothalamic pro-opiomelanocortin(POMC)and prodynorphin(PDYN)mRNA expressions and plasmaβ-endorphin(β-EP)content in rheumatoid arthritis(RA)rats,to understand the mechanism of moxibustion analgesia and its dose-effect relationship.METHODS:Twelve male Wistar rats were randomly selected from 48 male Wistar rats as a normal control group.The RA model was created by raising rats in a windy(blowing with electric fan),cold(6℃±2℃),and wet(80%-90%humidity)environment for 20 days,12 h each day.This was followed byinjectionofFreund'scompleteadjuvant(0.15 mL)into the ankle.Then,rats were randomly divided into a model group,moxibustion groupⅠ,and moxibustion groupⅡ,with 12 rats in each group.In moxibustion groupsⅠandⅡ,moxibustion was given at Shenshu(BL 23)and Zusanli(ST 36)for 20and 40 min,respectively,once daily for 15 days.Hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content were determined.RESULTS:Compared with the normal group,the pressure pain threshold decreased,while the hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content increased in the moxibustion groups(P<0.01).Compared with the model group,the pressure pain threshold,hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content in the moxibustion groups increased significantly(P<0.01).Compared the moxibustion groupⅠ,the pain threshold,hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content in moxibustion groupⅡsignificantly increased(P<0.01).CONCLUSION:Moxibustion has an analgesic effect and increases hypothalamic POMC and PDYN mRNA expression levels and plasmaβ-EP content inRArats.TheanalgesiceffectinmoxibustiongroupⅡisbetterthanthatinmoxibustiongroupⅠ.
基金Shanghai University of Traditional Chinese Medicine(上海中医药大学预算内课题,2015YSN13)The Three-year Development Project for Traditional Chinese Medicine of Shanghai(上海市进一步加快中医药事业发展三年行动计划项目,ZY(2018-2020)-CCCX-2001-05).
文摘Objective:To explore the central neurobiological mechanisms of pleasure effect on rats with neuralgia treated by tuina manipulations of An-pressing and Rou-kneading Huantiao (GB 30).Methods:A total of 64 male Sprague-Dawley (SD) rats were used in this study.Eighteen rats were randomly selected as a normal group,and the other 46 rats were used to duplicate the chronic constriction injury (CCI) model.Ten rats failed in modeling and 36 rats succeeded.These 36 rats were then randomly divided into a model group and a tuina group,with 18 rats in each group.The rats in the normal group and the model group did not receive any interventions,while those in the tuina group received An-pressing and Rou-kneading Huantiao (GB 30),1 min for each time,once a day,3 weeks in total.Heating tests were evaluated to observe the change of pain-sensitivity score before intervention,1 week after intervention,2 weeks after intervention,and 3 weeks after intervention.After 1 week of intervention,2 weeks of intervention,and 3 weeks of intervention,6 rats were randomly selected from each group respectively for brain extraction.The change of Nissl's body and β-endorphin in the accumbens nucleus as well as amygdaloid nucleus of pleasure circuits,and pro-opiomelanocortin (POMC) in the arcuate nucleus were analyzed by methods of histochemistry and molecular biology.Results:After modeling,the pain-sensitivity scores of the tuina group and the model group were statistically different from the score of the normal group (both P<0.05).After An-pressing and Rou-kneading Huantiao (GB 30) for one week,the pain-sensitivity score of the tuina group had statistical difference compared with that of the model group (P<0.05).At each different time point:the amounts of Nissl's body in accumbens nucleus and amygdaloid nucleus of the tuina group were significantly more than those of the model group (all P<0.01).Besides,the numbers of β-endorphin immunoreactive cells in the accumbens nucleus and amygdaloid nucleus of the rats in the tuina group were significant
基金supported by the National Natural Science Foundation of China(No.21677166)the National Key Research and Development Program of China(No.2018YFA0901103)。
文摘Fragmented data suggest that bisphenol AF(BPAF),a chemical widely used in a variety of products,might have potential impacts on the hypothalamus.Here,we employed male neonatal mice following maternal exposure to explore the effects of low-dose BPAF on hypothalamic development by RNA-sequencing.We found that maternal exposure to approximately 50μg/(kg·day)BPAF from postanal day(PND)0 to PND 15 altered the hypothalamic transcriptome,primarily involving the pathways and genes associated with extracellular matrix(ECM)and intercellular adhesion,neuroendocrine regulation,and neurological processes.Further RNA analysis confirmed the changes in the expression levels of concerned genes.Importantly,we further revealed that low-dose BPAF posed a stimulatory impact on pro-opiomelanocortin(POMC)neurons in the arcuate nucleus of the hypothalamus and induced the browning of inguinal white adipose tissue.All findings indicate that developmental exposure to low-dose BPAF could interfere with hypothalamic development and thereby lead to alterations in the metabolism.Interestingly,5000μg/(kg·day)BPAF caused slighter,non-significant or even inverse alterations than the low dose of 50μg/(kg·day),displaying a dose-independent effect.Further observations suggest that the the dose-independent effects of BPAF might be associated with oxidative stress and inflammatory responses caused by the high dose.Overall,our study highlights a risk of low-dose BPAF to human neuroendocrine regulation and metabolism.
基金We are grateful for the technical support of the Molecular Phenotyping,Histopathology and Histomorphometry,Confocal Microscopy,and Physiology Core facilities at MaineHealth Institute for Research.These core facilities are supported by grants P30GM106391,U54GM115516,and P20GM121301 from the National Institute of General Medical SciencesThis work was supported by grant DK095908(to A.H.)from the National Institute of Diabetes,Digestive and Kidney Diseases,National Institutes of Health,USA.
文摘Thyroid hormone excess secondary to global type 3 deiodinase(DIO3)deficiency leads to increased locomotor activity and reduced adiposity,but also to concurrent alterations in parameters of the leptin-melanocortin system that would predict obesity.To distinguish the underlying contributions to the energy balance phenotype of Dlo3 deficiency,we generated mice with thyroid hormone excess targeted to pro-opiomelanocortin(POMC)-expressing cells via cell-specific DIO3 inactivation.These mice exhibit a male-specific phenotype of reduced hypothalamic Pomc expression,hyperphagia,and increased activity in brown adipose tissue,with adiposity and serum levels of leptin and thyroid hormones remained normal.These male mice also manifest a marked and widespread hypothalamic reduction in the expression of bone morphogenetic receptor 1a(BMPR1A),which has been shown to cause similar phenotypes when inactivated in PoMC-expressing cells.Our results indicate that developmental overexposure to thyroid hormone in PoMC-expressing cells programs energy balance mechanisms in a sexually dimorphic manner by suppressing adult hypothalamic BMPR1A expression.
