In response to spinal surgery,neurons secrete a large amount of substance P into the epidural area.Substance P is involved in macrophage differentiation and fibrotic disease.However,the specific roles and mechanisms o...In response to spinal surgery,neurons secrete a large amount of substance P into the epidural area.Substance P is involved in macrophage differentiation and fibrotic disease.However,the specific roles and mechanisms of substance P in epidural fibrosis remain unclear.In this study,we established a mouse model of L1–L3 laminectomy and found that dorsal root ganglion neurons and the macrophages infiltrating into the wound area released sphingolipids.In vitro experiments revealed that type 1 macrophages secreted substance P,which promoted differentiation of type 1 macrophages towards a type 2 phenotype.High-throughput mRNA-seq analysis revealed that the sphingolipid metabolic pathway may be involved in the regulation of type 2 macrophages by substance P.Specifically,sphingomyelin synthase 2,a component of the sphingolipid metabolic pathway,promoted M2 differentiation in substance P-treated macrophages,while treating the macrophages with LY93,a sphingomyelin synthase 2 inhibitor,suppressed M2 differentiation.In addition,substance P promoted the formation of neutrophil extracellular traps,which further boosted M2 differentiation.Blocking substance P with the neurokinin receptor 1 inhibitor RP67580 decreased the number of M2 macrophages in the wound area after spinal surgery and alleviated epidural fibrosis,as evidenced by decreased fibronectin,α-smooth muscle actin,and collagen I in the scar tissue.These results demonstrated that substance P promotes M2 macrophage differentiation in epidural fibrosis via sphingomyelin synthase 2 and neutrophil extracellular traps.These findings provide a novel strategy for the treatment of epidural fibrosis.展开更多
Immunoreactive substance P(Ir-SP)level,and substance P likeimmunoreactivity(SP-Li)in the spinal cord were observed with radioimmunoassay andimmunohistochemistry in rats after they were given an intraperitoneal injecti...Immunoreactive substance P(Ir-SP)level,and substance P likeimmunoreactivity(SP-Li)in the spinal cord were observed with radioimmunoassay andimmunohistochemistry in rats after they were given an intraperitoneal injection of mor-phine(7.5mg/kg)or electroacupunctured(3V and 3Hz)on the “Jiaji point”.It wasfound that the pain threshold(PT),Ir-SP level and SP-Li in the dorsal horn of the spi-nal cord were more significantly increased in the animals after the administration ofmorphine or electroacupuncture than in the control(P【0.05～0.01).The combined effectsof morphine and electropacupuncture were even more powerful than either of the agentswas administered singly.Naloxone could block the analgesic effect and the elevation ofIr-SP due to morphine or electroacupuncture.The findings suggest that there is a synergismbe tween morphine and electroacupuncture and the analgesic effect of the 2 depends uponthe increase of Ir-SP level of the spinal cord mediated through the opiate receptors.展开更多
Purpose: We compared serum substance P (SP) levels in underlying diseases and dysphagia, or its absence, in patients with cerebrovascular disease, neurodegenerative disease or Alzheimer’s disease, to investigate the ...Purpose: We compared serum substance P (SP) levels in underlying diseases and dysphagia, or its absence, in patients with cerebrovascular disease, neurodegenerative disease or Alzheimer’s disease, to investigate the relationship between dysphagia and serum SP in chronic central nervous disease. Methods: Subjects comprised 94 patients admitted to a hospital or nursing home during the 5 years between April 2007 and April 2012 with central nervous symptoms. Serum SP levels were measured by enzyme immunoassay, and video endoscopy using a nasal endoscope in all subjects to objectively evaluate swallowing function. Results: Serum SP level was very similar in central nervous disease without dysphagia and controls without central nervous disease. Conversely, serum SP level was significantly lower in central nervous disease with dysphagia. When comparing underlying diseases, serum SP was significantly lower in Parkinson’s disease than in other disease groups (cerebrovascular disease, Alzheimer’s disease). Looking at changes in serum SP levels over time after disease onset, SP level was significantly low in subjects without dysphagia at the time of onset who went on to develop dysphagia during the disease course, whereas serum SP level tended to be higher in subjects with dysphagia at the time of onset and improvement during the disease course. With Parkinson’s disease and cerebrovascular disease, serum SP was low, particularly in subjects thought to have severe damage to the basal ganglia. Conclusion: Serum SP is generally thought to decrease in patients with cerebrovascular disease accompanied by dysphagia, but these results suggest that serum SP levels can be expected to improve to some extent, even if dysphagia is present at disease onset, assuming, for example, that some basal ganglia function remains. Positive therapeutic interventions such as swallowing rehabilitation should be promoted in such patients, with the goal of improving swallowing function.展开更多
BACKGROUND： The neuropeptide, substance P, has various bioactivities and is widely distributed in the central nervous system. Substance P participates in neural transmission in the spinal cord and plays an important ...BACKGROUND： The neuropeptide, substance P, has various bioactivities and is widely distributed in the central nervous system. Substance P participates in neural transmission in the spinal cord and plays an important role in regeneration and repair of nerve injury. OBJECTIVE： To investigate substance P mRNA expression in the anterior horn of the spinal cord following brachial plexus injury. DESIGN, TIME AND SETTING： A molecular cell biology randomized controlled study was performed at the Department of Anatomy, Zhongshan Medical College, Sun Yat-sen University and the DaAn Gene Laboratory in May 2005. MATERIALS： A total of 29 adult male Sprague Dawley rats were randomly assigned to a control group （n = 5） and an injury group （n = 24）. METHODS： The injury group was divided into three subgroups. In subgroup A, the right seventh cervical vertebra （C7） anterior root was avulsed, and the residual nerve root at the distal end was removed. In subgroup B, the right C7 anterior root was avulsed, and the right C5 first thoracic vertebrae （T1） posterior root was incised. Thus afferent pathways of the posterior root that connected with the anterior horn motor neurons were blocked. In subgroup C, the right C7 anterior root was avulsed, and a right C56 hemisection was performed. Thus the descending fiber pathways of the cortex that connected with anterior horn motor neurons were blocked. In the control group, the C5-T1 vertebral plate was opened, and then the skin was sutured. MAIN OUTCOME MEASURE： Substance P mRNA expression in the anterior horn of the spinal cord was quantified using fluorescent quantitative reverse transcription-polymerase chain reaction. RESULTS： Substance P mRNA expression was low in the anterior horn of the rat spinal cord in the control group. Substance P mRNA expression in the anterior horn of the spinal cord was upregulated and was significantly higher in the injury group compared with the control group （P 〈 0.01）. Substance P mRNA expression was highest in subgroup B. CONCLUSION： Brachial plexus anterior root avulsion is responsible for increased substance P expression in the anterior horn of the rat spinal cord. Pathway disjunction in efferent fibers of the posterior root or cortex does not have an effect on substance P expression in the anterior horn of the spinal cord.展开更多
We sought to determine whether substance P receptors (SPR) exist in human placenta and if do their cellular localization in placental villi, and to supply morphological evidence for the functional significance of SP i...We sought to determine whether substance P receptors (SPR) exist in human placenta and if do their cellular localization in placental villi, and to supply morphological evidence for the functional significance of SP in placental and fetal development. Methods: Immunohistochemical ABC method was used in the experiment. Results: Both syncytiotrophoblasts and cytotrophoblasts, stromal cells, capillary endothelium, lymphocytes in capillary cavity, and all blood islet in cells early human placenta showed SPR immunoreactivity in cytoplasm but with negative nuclei. Conclusion: SP produced by placental villi mediated by SPR might be responsible for the synthesis and release of placental hormone, the development of capillaries and the regulation of microcirculation in placental villi and fetal immune function.展开更多
AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1...AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine(5-HT) and substance P(SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity.in normal rats and 4.5 ± 1.58 in IBS model rats(P < 0.001). However, the defecation frequency was significantly decreased(3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time(in seconds) of colon transit function was significantly increased(256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. CONCLUSION: TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS.展开更多
BACKGROUND： Substance P participates in pain transmission and modulation, suggesting a close association with migraine headaches. The clinical application of magnesium has been effective in treating migraines, and th...BACKGROUND： Substance P participates in pain transmission and modulation, suggesting a close association with migraine headaches. The clinical application of magnesium has been effective in treating migraines, and the action mechanisms underlying migraines correlate with substance P expression. OBJECTIVE： To analyze different magnesium doses on behavior and substance P mRNA expression in the midbrain of a rat migraine model, and to determine the action pathway of migraine treatment using magnesium. DESIGN, TIME AND SETTING： A completely randomized, controlled, animal experiment was performed at the Experimental Animal Center and Central Laboratory in the Second Hospital of Jilin University between 2007 and 2008. MATERIALS： Magnesium sulfate （25%） was supplied by Tianjin Pharmaceutical Jiaozuo, China. Nitroglycerin was provided by Shanxi Kangbao Biological, China. Substance P primer sequence was synthesized by TaKaRa Biotechnology （Dalian）, China. METHODS： A total of 36 healthy, adult, Wistar rats were randomly assigned to 6 groups： control, migraine, low- and high-dose magnesium sulfate treated, and low- and high-dose magnesium sulfate control, with 6 rats in each group. Migraines were induced by subcutaneous injection of 10 mg/kg nitroglycerin in the migraine and low- and high-dose magnesium sulfate treated groups, and 2 mL/kg physiological saline was administered to rats in the control and low- and high-dose of magnesium sulfate control groups. Five minutes following administration, rats in low-dose groups were intraperitoneally injected with 100 mg/kg magnesium sulfate, while those in high-dose groups were injected with 300 mg/kg magnesium sulfate. No interventions were administered to the control and migraine groups. MAIN OUTCOME MEASURES： At 2 hours after nitroglycerin injection, substance P mRNA expression in the rat midbrain was measured by real-time quantitative polymerase chain reaction. At 60-90 minutes after nitroglycerin injection, behavioral changes of pain were analyzed in the experimental rats. RESULTS： The migraine group exhibited significantly lower levels of substance P mRNA expression compared with the control group （P 〈 0.05）. Following magnesium sulfate injection, substance P mRNA expression increased, compared with the migraine and control groups （P 〈 0.05）. In the low- and high-dose magnesium sulfate treated groups, pain behavior was remarkably ameliorated, compared with the migraine group （P 〈 0.05）, particularly with the high-dose injection （P 〈 0.05）. CONCLUSION： Magnesium relieved pain behaviors in a rat migraine model in a dose-dependent manner, and the therapeutic effect was achieved in conjunction with increased substance P expression in the midbrain.展开更多
Pancreatic cancer is the fourth leading cause of cancer related-death for both men and women and the 1-and5-year relative survival rates are 25%and 6%,respectively.Thus,it is urgent to investigate new antitumor drugs ...Pancreatic cancer is the fourth leading cause of cancer related-death for both men and women and the 1-and5-year relative survival rates are 25%and 6%,respectively.Thus,it is urgent to investigate new antitumor drugs to improve the survival of pancreatic cancer patients.The peptide substance P(SP)has a widespread distribution throughout the body.After binding to the neurokinin-1(NK-1)receptor,SP regulates biological functions related to cancer,such as tumor cell proliferation,neoangiogenesis,the migration of tumor cells for invasion,infiltration and metastasis,and it exerts an antiapoptotic effects on tumor cells.It is known that the SP/NK-1 receptor system is involved in pancreatic cancer progression:(1)pancreatic cancer cells and samples express NK-1 receptors;(2)the NK-1 receptor is overexpressed in pancreatic cancer cells in comparison with non-tumor cells;(3)nanomolar concentrations of SP induce pancreatic cancer cell proliferation;(4)NK-1 receptor antagonists inhibit pancreatic cell proliferation in a concentration-dependent manner,at a certain concentration,these antagonists inhibit100%of tumor cells;(5)this antitumor action is medi-ated through the NK-1 receptor,and tumor cells die by apoptosis;and(6)NK-1 receptor antagonists inhibit angiogenesis in pancreatic cancer xenografts.All these data suggest that the SP/NK-1 receptor system could play an important role in the development of pancreatic cancer;that the NK-1 receptor could be a new promising therapeutic target in pancreatic cancer,and that NK-1 receptor antagonists could improve the treatment of pancreatic cancer.展开更多
AIM: To investigate the effect and mechanism of electro-acupuncture (EA) at ST25 and ST37 on irritable bowel syndrome (IBS) of rats. METHODS: A total of 21 male Sprague-Dawley rats were randomly divided into normal gr...AIM: To investigate the effect and mechanism of electro-acupuncture (EA) at ST25 and ST37 on irritable bowel syndrome (IBS) of rats. METHODS: A total of 21 male Sprague-Dawley rats were randomly divided into normal group, model group and EA group. A rat model of IBS was established by constraining the limbs and distending the colorectum of rats. Rats in EA group received bilateral EA at ST25 and ST37 with a sparse and intense waveform at a frequency of 2/50 Hz for 15 min, once a day for 7 d as a course. Rats in normal and model groups were stimulated by distending colorectum (CR). An abdominal withdrawal reflex (AWR) scoring system was used to evaluate improvements in visceral hypersensitivity. Toluidine blue-improved method, immunohistochemistry and radioimmunoassay were used to observe mucosal mast cells (MC), changes of substance P (SP) and substance P receptor (SPR) in colon and change of corticotropin-releasing hormone (CRH) in hypothalamus.RESULTS: The threshold of visceral sense was signif icantly lower in model group than in normal group,and significantly higher in EA group than in model group. The number of mucosal MC was greater in model group than in normal group and significantly smaller in EA group than in model group. The CRH level in hypothalamus of rats was signif icantly higher in model group than in normal group, which was remarkably decreased after electro-acupuncture treatment. The SP and SPR expression in colon of rats in model group was decreased after electro-acupuncture treatment. CONCLUSION: EA at ST25 and ST37 can decrease the number of mucosal MC and down-regulate the expression of CRH in hypothalamus, and the expression of SP and SPR in colon of rats with IBS.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82172486(to JL),82171738(to MSZ),81671563(to MSZ)Jiangsu Provincial Commission of Health and Family Planning,No.JSWST-028(to JL)+1 种基金"Six One"Project of Jiangsu Province,No.LGY2016018(to JL)Jiangsu Provincial Personnel Department"the Great of Six Talented Man Peak"Project,No.WSW-040(to JL)。
文摘In response to spinal surgery,neurons secrete a large amount of substance P into the epidural area.Substance P is involved in macrophage differentiation and fibrotic disease.However,the specific roles and mechanisms of substance P in epidural fibrosis remain unclear.In this study,we established a mouse model of L1–L3 laminectomy and found that dorsal root ganglion neurons and the macrophages infiltrating into the wound area released sphingolipids.In vitro experiments revealed that type 1 macrophages secreted substance P,which promoted differentiation of type 1 macrophages towards a type 2 phenotype.High-throughput mRNA-seq analysis revealed that the sphingolipid metabolic pathway may be involved in the regulation of type 2 macrophages by substance P.Specifically,sphingomyelin synthase 2,a component of the sphingolipid metabolic pathway,promoted M2 differentiation in substance P-treated macrophages,while treating the macrophages with LY93,a sphingomyelin synthase 2 inhibitor,suppressed M2 differentiation.In addition,substance P promoted the formation of neutrophil extracellular traps,which further boosted M2 differentiation.Blocking substance P with the neurokinin receptor 1 inhibitor RP67580 decreased the number of M2 macrophages in the wound area after spinal surgery and alleviated epidural fibrosis,as evidenced by decreased fibronectin,α-smooth muscle actin,and collagen I in the scar tissue.These results demonstrated that substance P promotes M2 macrophage differentiation in epidural fibrosis via sphingomyelin synthase 2 and neutrophil extracellular traps.These findings provide a novel strategy for the treatment of epidural fibrosis.
文摘Immunoreactive substance P(Ir-SP)level,and substance P likeimmunoreactivity(SP-Li)in the spinal cord were observed with radioimmunoassay andimmunohistochemistry in rats after they were given an intraperitoneal injection of mor-phine(7.5mg/kg)or electroacupunctured(3V and 3Hz)on the “Jiaji point”.It wasfound that the pain threshold(PT),Ir-SP level and SP-Li in the dorsal horn of the spi-nal cord were more significantly increased in the animals after the administration ofmorphine or electroacupuncture than in the control(P【0.05～0.01).The combined effectsof morphine and electropacupuncture were even more powerful than either of the agentswas administered singly.Naloxone could block the analgesic effect and the elevation ofIr-SP due to morphine or electroacupuncture.The findings suggest that there is a synergismbe tween morphine and electroacupuncture and the analgesic effect of the 2 depends uponthe increase of Ir-SP level of the spinal cord mediated through the opiate receptors.
文摘Purpose: We compared serum substance P (SP) levels in underlying diseases and dysphagia, or its absence, in patients with cerebrovascular disease, neurodegenerative disease or Alzheimer’s disease, to investigate the relationship between dysphagia and serum SP in chronic central nervous disease. Methods: Subjects comprised 94 patients admitted to a hospital or nursing home during the 5 years between April 2007 and April 2012 with central nervous symptoms. Serum SP levels were measured by enzyme immunoassay, and video endoscopy using a nasal endoscope in all subjects to objectively evaluate swallowing function. Results: Serum SP level was very similar in central nervous disease without dysphagia and controls without central nervous disease. Conversely, serum SP level was significantly lower in central nervous disease with dysphagia. When comparing underlying diseases, serum SP was significantly lower in Parkinson’s disease than in other disease groups (cerebrovascular disease, Alzheimer’s disease). Looking at changes in serum SP levels over time after disease onset, SP level was significantly low in subjects without dysphagia at the time of onset who went on to develop dysphagia during the disease course, whereas serum SP level tended to be higher in subjects with dysphagia at the time of onset and improvement during the disease course. With Parkinson’s disease and cerebrovascular disease, serum SP was low, particularly in subjects thought to have severe damage to the basal ganglia. Conclusion: Serum SP is generally thought to decrease in patients with cerebrovascular disease accompanied by dysphagia, but these results suggest that serum SP levels can be expected to improve to some extent, even if dysphagia is present at disease onset, assuming, for example, that some basal ganglia function remains. Positive therapeutic interventions such as swallowing rehabilitation should be promoted in such patients, with the goal of improving swallowing function.
文摘BACKGROUND： The neuropeptide, substance P, has various bioactivities and is widely distributed in the central nervous system. Substance P participates in neural transmission in the spinal cord and plays an important role in regeneration and repair of nerve injury. OBJECTIVE： To investigate substance P mRNA expression in the anterior horn of the spinal cord following brachial plexus injury. DESIGN, TIME AND SETTING： A molecular cell biology randomized controlled study was performed at the Department of Anatomy, Zhongshan Medical College, Sun Yat-sen University and the DaAn Gene Laboratory in May 2005. MATERIALS： A total of 29 adult male Sprague Dawley rats were randomly assigned to a control group （n = 5） and an injury group （n = 24）. METHODS： The injury group was divided into three subgroups. In subgroup A, the right seventh cervical vertebra （C7） anterior root was avulsed, and the residual nerve root at the distal end was removed. In subgroup B, the right C7 anterior root was avulsed, and the right C5 first thoracic vertebrae （T1） posterior root was incised. Thus afferent pathways of the posterior root that connected with the anterior horn motor neurons were blocked. In subgroup C, the right C7 anterior root was avulsed, and a right C56 hemisection was performed. Thus the descending fiber pathways of the cortex that connected with anterior horn motor neurons were blocked. In the control group, the C5-T1 vertebral plate was opened, and then the skin was sutured. MAIN OUTCOME MEASURE： Substance P mRNA expression in the anterior horn of the spinal cord was quantified using fluorescent quantitative reverse transcription-polymerase chain reaction. RESULTS： Substance P mRNA expression was low in the anterior horn of the rat spinal cord in the control group. Substance P mRNA expression in the anterior horn of the spinal cord was upregulated and was significantly higher in the injury group compared with the control group （P 〈 0.01）. Substance P mRNA expression was highest in subgroup B. CONCLUSION： Brachial plexus anterior root avulsion is responsible for increased substance P expression in the anterior horn of the rat spinal cord. Pathway disjunction in efferent fibers of the posterior root or cortex does not have an effect on substance P expression in the anterior horn of the spinal cord.
文摘We sought to determine whether substance P receptors (SPR) exist in human placenta and if do their cellular localization in placental villi, and to supply morphological evidence for the functional significance of SP in placental and fetal development. Methods: Immunohistochemical ABC method was used in the experiment. Results: Both syncytiotrophoblasts and cytotrophoblasts, stromal cells, capillary endothelium, lymphocytes in capillary cavity, and all blood islet in cells early human placenta showed SPR immunoreactivity in cytoplasm but with negative nuclei. Conclusion: SP produced by placental villi mediated by SPR might be responsible for the synthesis and release of placental hormone, the development of capillaries and the regulation of microcirculation in placental villi and fetal immune function.
基金Supported by National Education Department"ChunHui Plan"Research Projects,No.Z2010021China Postdoctoral Science Foundation Project,No.2013M531079+2 种基金Heilongjiang Postdoctoral Funding Project,No.LBH-Z12246Heilongjiang Education Department Scientific Research Project,No.12521502excellent Innovative Talents Support Program Funding of Heilongjiang University of Chinese Medicine(Outstanding Young Academic Leaders),No.051217
文摘AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine(5-HT) and substance P(SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity.in normal rats and 4.5 ± 1.58 in IBS model rats(P < 0.001). However, the defecation frequency was significantly decreased(3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time(in seconds) of colon transit function was significantly increased(256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. CONCLUSION: TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS.
基金a grant by Jilin Provincial Science and Technology Bureau,No. 200705238
文摘BACKGROUND： Substance P participates in pain transmission and modulation, suggesting a close association with migraine headaches. The clinical application of magnesium has been effective in treating migraines, and the action mechanisms underlying migraines correlate with substance P expression. OBJECTIVE： To analyze different magnesium doses on behavior and substance P mRNA expression in the midbrain of a rat migraine model, and to determine the action pathway of migraine treatment using magnesium. DESIGN, TIME AND SETTING： A completely randomized, controlled, animal experiment was performed at the Experimental Animal Center and Central Laboratory in the Second Hospital of Jilin University between 2007 and 2008. MATERIALS： Magnesium sulfate （25%） was supplied by Tianjin Pharmaceutical Jiaozuo, China. Nitroglycerin was provided by Shanxi Kangbao Biological, China. Substance P primer sequence was synthesized by TaKaRa Biotechnology （Dalian）, China. METHODS： A total of 36 healthy, adult, Wistar rats were randomly assigned to 6 groups： control, migraine, low- and high-dose magnesium sulfate treated, and low- and high-dose magnesium sulfate control, with 6 rats in each group. Migraines were induced by subcutaneous injection of 10 mg/kg nitroglycerin in the migraine and low- and high-dose magnesium sulfate treated groups, and 2 mL/kg physiological saline was administered to rats in the control and low- and high-dose of magnesium sulfate control groups. Five minutes following administration, rats in low-dose groups were intraperitoneally injected with 100 mg/kg magnesium sulfate, while those in high-dose groups were injected with 300 mg/kg magnesium sulfate. No interventions were administered to the control and migraine groups. MAIN OUTCOME MEASURES： At 2 hours after nitroglycerin injection, substance P mRNA expression in the rat midbrain was measured by real-time quantitative polymerase chain reaction. At 60-90 minutes after nitroglycerin injection, behavioral changes of pain were analyzed in the experimental rats. RESULTS： The migraine group exhibited significantly lower levels of substance P mRNA expression compared with the control group （P 〈 0.05）. Following magnesium sulfate injection, substance P mRNA expression increased, compared with the migraine and control groups （P 〈 0.05）. In the low- and high-dose magnesium sulfate treated groups, pain behavior was remarkably ameliorated, compared with the migraine group （P 〈 0.05）, particularly with the high-dose injection （P 〈 0.05）. CONCLUSION： Magnesium relieved pain behaviors in a rat migraine model in a dose-dependent manner, and the therapeutic effect was achieved in conjunction with increased substance P expression in the midbrain.
文摘Pancreatic cancer is the fourth leading cause of cancer related-death for both men and women and the 1-and5-year relative survival rates are 25%and 6%,respectively.Thus,it is urgent to investigate new antitumor drugs to improve the survival of pancreatic cancer patients.The peptide substance P(SP)has a widespread distribution throughout the body.After binding to the neurokinin-1(NK-1)receptor,SP regulates biological functions related to cancer,such as tumor cell proliferation,neoangiogenesis,the migration of tumor cells for invasion,infiltration and metastasis,and it exerts an antiapoptotic effects on tumor cells.It is known that the SP/NK-1 receptor system is involved in pancreatic cancer progression:(1)pancreatic cancer cells and samples express NK-1 receptors;(2)the NK-1 receptor is overexpressed in pancreatic cancer cells in comparison with non-tumor cells;(3)nanomolar concentrations of SP induce pancreatic cancer cell proliferation;(4)NK-1 receptor antagonists inhibit pancreatic cell proliferation in a concentration-dependent manner,at a certain concentration,these antagonists inhibit100%of tumor cells;(5)this antitumor action is medi-ated through the NK-1 receptor,and tumor cells die by apoptosis;and(6)NK-1 receptor antagonists inhibit angiogenesis in pancreatic cancer xenografts.All these data suggest that the SP/NK-1 receptor system could play an important role in the development of pancreatic cancer;that the NK-1 receptor could be a new promising therapeutic target in pancreatic cancer,and that NK-1 receptor antagonists could improve the treatment of pancreatic cancer.
基金Supported by Open Fund of Key Laboratory of Acupuncture Combined with Medication (Nanjing University of TCM), Ministry of Education, No. KJA200809Shanghai Rising-Star Program, No. 08QA14064Shanghai Leading Academic Discipline Project, No. S30304
文摘AIM: To investigate the effect and mechanism of electro-acupuncture (EA) at ST25 and ST37 on irritable bowel syndrome (IBS) of rats. METHODS: A total of 21 male Sprague-Dawley rats were randomly divided into normal group, model group and EA group. A rat model of IBS was established by constraining the limbs and distending the colorectum of rats. Rats in EA group received bilateral EA at ST25 and ST37 with a sparse and intense waveform at a frequency of 2/50 Hz for 15 min, once a day for 7 d as a course. Rats in normal and model groups were stimulated by distending colorectum (CR). An abdominal withdrawal reflex (AWR) scoring system was used to evaluate improvements in visceral hypersensitivity. Toluidine blue-improved method, immunohistochemistry and radioimmunoassay were used to observe mucosal mast cells (MC), changes of substance P (SP) and substance P receptor (SPR) in colon and change of corticotropin-releasing hormone (CRH) in hypothalamus.RESULTS: The threshold of visceral sense was signif icantly lower in model group than in normal group,and significantly higher in EA group than in model group. The number of mucosal MC was greater in model group than in normal group and significantly smaller in EA group than in model group. The CRH level in hypothalamus of rats was signif icantly higher in model group than in normal group, which was remarkably decreased after electro-acupuncture treatment. The SP and SPR expression in colon of rats in model group was decreased after electro-acupuncture treatment. CONCLUSION: EA at ST25 and ST37 can decrease the number of mucosal MC and down-regulate the expression of CRH in hypothalamus, and the expression of SP and SPR in colon of rats with IBS.
