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Para avaliar o papel da pregabalina na proteção das náuseas e vômitos induzidos pela quimioterapia, foi realizado um ensaio clínico de fase II, aleatorizado, duplamente cego, controlado por placebo, para investigar se a pregabalina poderia melhorar o controle completo das náuseas e vômitos (desfecho primário). Inscrevemos 82 pacientes virgens de quimioterapia, programados para receber quimioterapia moderadamente e altamente emetogênica. Todos os doentes receberam ondansetron 8mg por via intravenosa, dexametasona 10mg antes da quimioterapia no primeiro dia e, dexametasona 4 mg por via oral, b.d., nos dias dois e três. Os doentes foram distribuídos aleatoriamente para tomar pregabalina 75 mg ou placebo, bd, desde a noite anterior à quimioterapia até ao quinto dia. A resposta completa global não foi estatisticamente significativa entre os grupos (53,7 versus 48,8%, respetivamente, no grupo da pregabalina e no grupo de controlo (P=0,65)). Também não houve diferença estatística significativa durante a fase aguda (primeiras 24 horas) e a fase tardia (24-120h): 80,5% versus 82,9% (P=0,77), 53,7 versus 51,2% (P=0,82), respectivamente. Neste estudo não foi identificada ação da pregabalina na prevenção de náuseas e vômitos induzidos por quimioterapia. Número de registo no Clinicaltrial.gov: NCT04181346.
To evaluate the role of pregabalin in the protection of chemotherapy-induced nausea and vomiting, we performed a phase II randomized, double-blind, placebo-controlled trial to investigate whether pregabalin could improve the complete control of nausea and vomiting (primary end point). We enrolled 82 chemotherapy-naive patients, scheduled to receive moderately and highly emetogenic chemotherapy. All patients received IV ondansetron 8mg, dexamethasone 10mg before chemotherapy on day one and oral dexamethasone 4mg, b.d., on days two and three. Patients were randomly assigned to take pregabalin 75mg or placebo, bd, from the night before chemotherapy to day five. The overall complete response was not statistically significant between the groups (53.7 versus 48.8%, respectively, in the pregabalin group and the control group (P=0.65)). There was also no significant difference during the acute phase (first 24 hours) and delayed phase (24-120h): 80.5% versus 82.9% (P=0.77), 53.7 versus 51.2% (P=0.82), respectively. There is no role for pregabalin preventing chemotherapy-induced nausea and vomiting. Clinicaltrial.gov registration number: NCT04181346.
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OBJECTIVE To evaluate the efficacy of the triple therapy of 5-HT3 receptor antagonists， neurokinin-1 receptor antagonists and dexamethasone （referred to as “triple therapy”） in the prevention and treatment of acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI and Wanfang data， randomized controlled trials （RCTs） about triple therapy or 5-HT3 receptor antagonist combined with dexamethasone （referred to as “dual therapy”） were collected during the inception to May 2023. After literature screening， data extraction and literature evaluation， network meta-analysis was performed by using Stata 16.0 software. RESULTS A total of 59 RCTs were included， involving 23 418 patients and 15 interventions. Results of network meta-analysis showed that fosaprepitant + palonosetron + dexamethasone （FPD） was most effective in terms of acute nausea and vomiting control rate， followed by fosaprepitant + granisetron + dexamethasone （FGD） and aprepitant + ramosetron + dexamethasone （AMD）. In terms of acute nausea control rate， FPD was the most effective， followed by aprepitant + palonosetron + dexamethasone （APD） and FGD. In terms of acute vomiting control rate， FPD was the most effective， followed by FGD and APD. CONCLUSIONS Fosaprepitant + palonosetron + dexamethasone is better than other triple therapy or dual therapy in preventing acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs.
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Objective@#To investigate the effects of neurokinin-1 receptor antagonist WIN 62, 577 on airway inflammation and airway hyperresponsiveness in asthmatic mice.@*Methods@#Thirty-two BALB/c mice(Specific-pathogen-free grade) were randomly divided into 4 groups: control group, asthmatic group, WIN 62, 577 intervention group and dexamethasone group.The asthmatic group, the WIN 62, 577 intervention group, and the dexamethasone group were given intraperitoneal injection of 0.2 ml of OVA sensitization solution at 0 d, 7 d, and 14 d, respectively.Then the asthmatic group, WIN 62, 577 group and dexamethasone group were given OVA challenge solution(4% OVA solution) by inhalation once a day for 30 min from 21 d to 28 d for 7 consecutive days.The WIN 62, 577 intervention group was given WIN 62, 577 300 μg intraperitoneal injection 1 h before each challenge; the dexamethasone group was given intraperitoneal injection of dexamethasone 2 mg/kg 1 h before each challenge.The airway responsiveness of each group of mice was detected by non-invasive pulmonary function test.The bronchoalveolar lavage fluid(BALF) was obtained for inflammatory count.The HE staining of lung tissue was used to observe airway inflammation in mice.@*Results@#Compared with the asthmatic group, the mice in the WIN 62, 577 intervention group showed less restlessness, standing upright, crouching back, scratching the ears and scratching the cheeks, shortness of breath and cyanosis of the lips.After inhaling different concentrations of acetylcholine, the Penh value of mice in the WIN 62, 577 intervention group and the dexamethasone group was significantly lower than that in the asthmatic group(P<0.05). Compared with the asthmatic group, the number of WBC and EOS in BALF decreased significantly in the WIN 62, 577 intervention group and the dexamethasone group(P<0.01). HE staining showed that the inflammatory changes in the lung tissue of mice in the WIN 62, 577 intervention group were significantly reduced, the bronchial epithelium did not fall off significantly, the mucosal edema was not obvious, the smooth muscle proliferation was reduced, and the inflammatory cell infiltration was reduced, similar to the airway changes in the dexamethasone group.@*Conclusion@#Neurokinin-1 receptor antagonist WIN 62, 577 can reduce airway inflammation and airway hyperresponsiveness in asthmatic mice.
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Substance P (SP) is the first identified peptide in tachykinin family, which widespreadly distributes in both central and peripheral nervous systems of mammals and is involved in many physiological and pathological processes. Neurokinin receptors (NKRs) belong to the G-protein coupled receptor family, including NK1R, NK2R and NK3R. SP has the highest affinity and is the selectivity ligand for NK1R. Cumulative experimental results have shown that SP/NK1R system is involved in the cancer process and NK1R has the potential to be a new target for cancer treatment. In this review, we focus on the expression levels of SP/NK1R system in cancers and how to develop SP/NK1R system as a new target for cancer treatment.
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Postoperative nausea and vomiting ( PONV) is a common complication after anaesthesia, which hinders the rapid recovery of patients. Aprepitant, one of neurokinin-1 (NK-1) receptor antagonists is mainly used to prevent nausea and vomiting by blocking the binding of substance P to NK-1 receptor. It has the advantages of high selectivity, strong affinity and long half-life, and its new antiemetic target pro-vides a new choice for prophylactic treatment of PONV. This article summarize studies on the prophylaxis of aprepitant in treatment of PONV.
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Objective To examine the effect of NK1 receptor ( NK1R) antagonist L-703,606 on ethanol-induced conditioned place preference (CPP) and levels of NK1R protein in different brain regions in juvenile mice. Methods Four-week-old male C57BL/6 mice were divided into high anxiety group and low anxiety group according to the percentage of time spent in open arms of elevated plus maze(EPM). Then the mice in the two groups were divided into control group and experimental group according to random number table,which were high anxiety control group,high anxiety experimental group,low anxiety control group and low anxiety experimental group,with 11 in each group. L-703,606 was injected intraperitoneally 40 minutes before CPP training in the high and low anxiety experimental group,while the control group received solvent treatment. After CPP test,the anxiety level of four groups of mice was detected by EPM again. The expres-sion of NK1R protein in hippocampus,prefrontal lobe and amygdala of mice was detected by Western blot. Results Compared with the high anxiety control group, the CPP value of the high anxiety experimental group was lower,and the difference was statistically significant ((77. 7 ± 9. 3) s vs (13. 6 ± 13. 0) s,P=0. 002). Compared with the low anxiety control group,the CPP value of the low anxiety experimental group was lower,and the difference was statistically significant ((113. 2±10. 3)s vs (28. 0±9. 6)s,P<0. 01). Af-ter L-703,606 treatment,there was no significant difference in the percentage of open arm time between the control group and experimental group either in high anxiety group or in low anxiety group (both P>0. 05) . Compared with the high anxiety control group,the expression of NK1R increased in hippocampus,prefrontal lobe and amygdala of mice in high anxiety experimental group (all P<0. 05). And the expression of NK1R in the above three brain regions had the same result between the low anxiety control group and the low anxiety experimental group (all P<0. 05). Conclusions L-703,606 can attenuate ethanol-induced CPP but has no effect on anxiety-like behaviors,suggesting the direct effect of NK1R in alcohol reward in juvenile mice.
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BACKGROUND: To identify a new strategy for postoperative pain management, we investigated the analgesic effects of allopregnanolone (Allo) in an incisional pain model, and also assessed its effects on the activities of the primary afferent fibers at the dorsal horn. METHODS: In experiment 1, 45 rats were assigned to Control, Allo small-dose (0.16 mg/kg), and Allo large-dose (1.6 mg/kg) groups (n = 15 in each). The weight bearing and mechanical withdrawal thresholds of the hind limb were measured before and at 2, 24, 48, and 168 h after Brennan's surgery. In experiment 2, 16 rats were assigned to Control and Allo (0.16 mg/kg) groups (n = 8 in each). The degree of spontaneous pain was measured using the grimace scale after the surgery. Activities of the primary afferent fibers in the spinal cord (L6) were evaluated using immunohistochemical staining. RESULTS: In experiment 1, the withdrawal threshold of the Allo small-dose group was significantly higher than that of the Control group at 2 h after surgery. Intergroup differences in weight bearing were not significant. In experiment 2, intergroup differences in the grimace scale scores were not significant. Substance P release in the Allo (0.16 mg/kg) group was significantly lower than that in the Control group. CONCLUSIONS: Systemic administration of Allo inhibited mechanical allodynia and activities of the primary afferent fibers at the dorsal horn in a rat postoperative pain model. Allo was proposed as a candidate for postoperative pain management.
Subject(s)
Animals , Rats , Extremities , Hyperalgesia , Pain, Postoperative , Pregnanolone , Receptors, Neurokinin-1 , Spinal Cord , Spinal Cord Dorsal Horn , Substance P , Weight-BearingABSTRACT
Objective:To investigate the effect of miRNA-34b/c-5p on the expression of neurokinin 1 receptor-truncated(NK1R-Tr)in breast cancer and the effect of miRNA-34b/c-5p and NK1R-Tr on the migration and invasion abilities of breast cancer cells.Methods:Real-time fluorescence quantitative PCR(RT-PCR)was used to detect the expression of miRNA-34b/c-5p and NK1R-Tr in 50 breast can-cer specimens that were collected at Tianjin Medical University Cancer Institute&Hospital from February to May 2013.Western blot analysis was performed to detect the expression of miRNA-34b/c-5p and NK1R-Tr in breast cancer cell lines MDA-MB-231 and MCF-7. Scratch and Transwell assays were carried out to explore the effects of miRNA-34b/c-5p and NK1R-Tr on the migration and invasion abilities of MDA-MB-231 cells.Results:The expression of miRNA-34b/c-5p and NK1R-Tr in breast cancer tissues and cells were signifi-cantly negatively correlated.The relative expression of NK1R-Tr in breast cancer patients with lymph node metastasis was 5.75,and the relative expression of NK1R-Tr in patients with non-lymph node metastasis was 4.29.The relative expression was significantly dif-ferent between the two groups(P=0.026).Overexpression of miRNA-34b/c-5p and knockdown of NK1R-Tr could significantly inhibit the migration and invasion abilities of MDA-MB-231 cells(all P<0.001).Conclusions:The expression of miRNA-34b/c-5p and NK1R-Tr was significantly negatively correlated.MiRNA-34b/c-5p and NK1R-Tr might be potential therapeutic targets for inhibiting the invasion of breast cancer cells.
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<p><b>Objective</b>To investigate the expressions of substance P (SP) and neurokinin-1 receptor (NK-1R) in the posterior horn of the L5－S2 spinal cord in the rat model of chronic nonbacterial prostatitis (CNP) at different time points of modeling.</p><p><b>METHODS</b>Forty adult male SD rats were randomly divided into four groups of equal number, control, 45 d model, 60 d model, and 90 d model, and proteins were obtained from the prostatic tissue of another 30 rats. The CNP model was made by intraperitoneal injection of 0.5 ml DPT vaccineand intradermal injection of mixed solution of 1 ml prostatein extract and complete adjuvant at a 1∶1 ratio, while the control rats were injected with the same volume of normal saline. At 45, 60, and 90 days after modeling, we measured the paw withdrawal threshold (PWT) of the rats, determined the levels of TNF-α, IL-1β, IL-2, and IL-10 in the prostate tissue by ELISA, observed the histomorphological changes in the prostate by transmission electron and light microscopy, and detected the expressions of SP and NK1-R in the L5－S2 spinal cord by immunohistochemistry.</p><p><b>RESULTS</b>The model rats showed significantly increased sensitivity to pain, with remarkably lowered PWT at 45, 60, and 90 days after modeling. The levels of TNF-α, IL-1β, IL-2, and IL-10 in the prostate tissue were markedly elevated in the CNP models as compared with those in the controls (all P<0.05), most significantly at 90 days (all P<0.05). Immunohistochemistry showed that the expressions of SP and NK-1R were remarkably higher in the CNP model groups than in the control (all P<0.05), the highest at 90 days. Light microscopy revealed no inflammatory cell infiltration in the prostate tissue of the control rats, and obvious edema and increased lymphocytes were observed with the prolonged time of modeling.Transmission electron microscopy showed inflammatory changes in the prostate tissue of the model rats and that peritubular interstitial edema was most obvious at 90 days, with widened intervals between peritubular cells and the epithelial base and increased numbers of fibroblasts and collagen fibrils.</p><p><b>CONCLUSIONS</b>The synthesis of SP and the level of NK-1R were increased in the posterior horn of the L5－S2 spinal cord in the rat model of CNP.</p>
Subject(s)
Animals , Male , Rats , Interleukin-10 , Metabolism , Interleukin-1beta , Metabolism , Interleukin-2 , Metabolism , Pain , Prostatitis , Metabolism , Random Allocation , Rats, Sprague-Dawley , Receptors, Neurokinin-1 , Metabolism , Spinal Cord , Metabolism , Substance P , Metabolism , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
Objective:To observe the effects of salidroside on the expression of substance P (SP)and neurokinin-1 receptor (NK-1R)of bone marrow cells(BMCs)in bone marrow(BM)depressed anemia mice,and to explore its roles for hematopoietic regulation.Methods:Automatic blood cell analysator was used to detected the changes of peripheral blood cells in each group ,immuno-histochemistry and reverse transcription-polymerase chain reaction ( RT-PCR) were used to analyze the expressions of SP and its receptor NK-1R of BMCs in each group respectively.Results: Peripheral blood testing results showed that the number of white blood cells (WBC),red blood cells(RBC)and hemoglobin(HB)of model group were significantly decreased when compared with control group.Compared with model group ,low-dose,middle-dose and high-dose salidroside obviously elevated the number of white blood cells ,and middle-dose salidroside obviously elevated the number of platelets.Immunohistochemistry studies showed that the expression of SP and its receptor NK-1R of BMCs was found in each group.Compared with control group , the expression of SP of BMCs was decreased obviously in model group(P0.05),and the expression of SP and its receptor NK-1R of BMCs was increased significantly in low-dose,middle-dose and high-dose salidroside groups (P<0.05).RT-PCR data showed that the expression of SP mRNA of BMCs was increased obviously in model group ,low-dose,middle-dose and high-dose salidroside groups when compared with control group (P<0.05).The expression of NK-1R mRNA of BMCs was un-detected in control group and model group.The expression level of NK-1R mRNA of BMCs was elevated gradually with the increase of salidroside dosage in low-dose,middle-dose and high-dose salidroside groups.Conclusion: The mRNA and protein expressions of SP and its receptor NK-1R of BMCs were up-regulated significantly by salidroside in dose-dependent manner.These data suggest that salidroside could participate in the recovery of hematopoietic function of BM depressed anemia mice by increasing the expression of SP and its receptor NK-1R of BMCs.
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Objective:To determine the expression of the full-length (NK1R-FL) and truncated (NK1R-Tr) neurokinin-1 receptor (NK1R) and the neurokinin-2 receptor (NK2R) in breast cancer tissues and cell lines, as well as to study the effects of the NK1R and NK2R antagonists on the growth of breast cancer cells. Methods:Immunohistochemistry and Western blot assays were used to detect NK1R, NK1R-FL, and NK2R expression in clinical samples of primary breast cancer tissue, benign lesions, and normal breast tissue, as well as in different breast cancer cell lines. Cell proliferation and soft agar growth tests were performed on cells treated with the NK1R and NK2R antagonists to study the ectopic overexpression of NK1R-FL and NK1R-Tr in breast cancer cell lines. Results:Total NK1R expression was detected in the breast cancer tissues, benign lesions, and normal breast tissues. Compared with the normal breast epithe-lia and benign breast lesions, the expression levels of NK1R-FL and NK2R decreased in the carcinoma. These changes were also relat-ed to the carcinoma type, histological grade, lymph node metastasis, HER2 and Ki-67 expression, and estrogen and progesterone recep-tors in breast cancer. The expression levels of NK1R-FL and NK2R were high in the HBL-100 breast cell lines of para-neoplastic tis-sues, but NK1R-Tr expression was low. The MDA-MB-231, T-47D, and MCF-7 cells only expressed NK1R-Tr. NK1R-Tr or NK1R-FL overexpression caused the decreased inhibition rate or increased levels of the NK1R and NK2R antagonists in the breast cancer cells. Conclusion:NK1R-FL and NK2R are co-expressed in normal cells. NK1R-Tr is highly expressed in breast cancer cells and exerts nega-tive feedback to regulate NK1R-FL and NK2R expression in all cells, especially cancer cells.
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BACKGROUND: The purpose of this study was to evaluate the effect of an aprepitant, neurokinin-1(NK1) receptor antagonist, for reducing postoperative nausea and vomiting (PONV) for up to 24 hours in patients regarded as high risk undergoing gynecological surgery with intravenous patient-controlled analgesia (IV PCA) using fentanyl. METHODS: In this randomized, open label, case-control study 84 gynecological surgical patients receiving a standardized general anesthesia were investigated. Patients were randomly allocated to receive aprepitant 80 mg P.O. approximately 2-3 hours before operation (aprepitant group) or none (control group). All patients received ramosetron 0.3 mg IV after induction of anesthesia. The incidence of PONV, severity of nausea, and use of rescue antiemetics were evaluated for up to 24 hours postoperatively. RESULTS: The incidence of nausea was significantly lower in the aprepitant group (50.0%) compared to the control group (80.9%) during the first 24 hours following surgery. The incidence of vomiting was significantly lower in the aprepitant group (4.7%) compared to the control group (42.8%) during the first 24 hours following surgery. In addition, the severity of nausea was less among those in the aprepitant group compared with the control group over a period of 24 hours post-surgery (P < 0.05). Use of rescue antiemetics was lower in the aprepitant group than in the control group during 24 hours postoperatively (P < 0.05). CONCLUSIONS: In patients regarded as high risk undergoing gynecological surgery with IV PCA using fentanyl, the aprepitant plus ramosetron ware more effective than ramosetron alone to decrease the incidence of PONV, use of rescue antiemetics and nausea severity for up to 24 hours postoperatively.
Subject(s)
Female , Humans , Analgesia, Patient-Controlled , Anesthesia , Anesthesia, General , Anesthesia, Obstetrical , Antiemetics , Benzimidazoles , Case-Control Studies , Fentanyl , Gynecologic Surgical Procedures , Incidence , Morpholines , Nausea , Passive Cutaneous Anaphylaxis , Postoperative Nausea and Vomiting , Receptors, Neurokinin-1 , VomitingABSTRACT
Background: The fibrinolytic activity plays an important role in Peritoneal Adhesions (PA) develop-ment. It's well known that de substance P decreased the fibrinolysis by binding the neurokinin-1 receptor, improving the PA formation. Objectives: To evaluate the effectiveness of intraperitoneal treatment with a Neurokinin-1 receptor antagonist (NK-R1A) in peritoneal adhesión prevention in animal model. Materials and Methods: In 40 male wistar rats, PA were induced, and then randomly assigned to 2 groups: A group treated with Aprepitant (NK-Rl A), and a control group. The animals were killed at 7 or 14 postoperative day, and the number, severity and histopathology of PA were evaluated. Results: NK-Rl A decreased the number (40 percent less) and severity (p = 0.001) of PA when compare to control group. The NK-Rl A group had less PA in manipulated and no manipulated organs during surgery. Besides presented less fibrosis (p = 0.001), less inflamation (p = 0.005) and less vascular proliferation (p = 0.047) than control group. Conclusions: The NK-Rl A is effective as in PA prevention.
Introducción: La actividad fibrinolítica juega un papel fundamental en el desarrollo de las adherencias peritoneales (AP), y se conoce que la Sustancia P al actuar sobre receptores de neurokinina tipo 1 a nivel peritoneal, disminuye la fibrinólisis, favoreciendo la formación de las mismas. Objetivos: Evaluar la efectividad del tratamiento intraperitoneal con antagonista de receptores 1 de neurokinina (NK-R1A) en la prevención de AP en modelo animal. Materiales y Métodos: A 40 ratas wistar se les practicó cirugía formadora de AP y fueron distribuidas de forma aleatoria en 2 grupos, un grupo que recibió Aprepitant (NK-R1A), y el otro como grupo control. Los animales fueron sacrificados a los 7 ó 14 días, y se evaluó el número, severidad e histopatología de las AP. Resultados: El NK-Rl A disminuyó el número (40 por ciento menos) y severidad de las AP (p = 0,001) en relación al grupo control y presentó menos AP en órganos manipulados y no manipulados durante la cirugía. Ademßs presentó menor grado de fibrosis (p = 0,001), menor inflamación (p = 0,005) y menor proliferación vascular (p = 0,047) que el grupo control. Conclusión: El tratamiento peritoneal con NK-R1A es eficaz en la prevención de la formación de AP.
Subject(s)
Animals , Male , Rats , Postoperative Complications/prevention & control , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Peritoneal Diseases/prevention & control , Receptors, Neurokinin-1/antagonists & inhibitors , Fibrinolysis , Models, Biological , Rats, Wistar , Substance PABSTRACT
La actividad fibrinolítica juega un papel fundamental en el desarrollo de las adherencias peritoneales (AP), y se conoce que la sustancia P al actuar sobre receptores de neurokinina tipo 1 a nivel peritoneal, disminuyen la fibrinólisis, favoreciendo la formación de las mismas. La efectividad de antagonistas de estos receptores como tratamiento preventivo de AP, ha sido evaluada, obteniendose resultados favorables. Comparar la efectividad del tratamiento intraperitoneal con antagonista de receptores 1 de neurokinina (NK-RIA) versus gel de ácido hialurónico/carboximetilcelulosa (AH/CMC) en la prevención de AP en modelo animal. A 60 ratas Wistar se les practicó cirugía formadora de AP y fueron distribuidas de forma aleatoria en 3 grupos, un grupo que recibió aprepitant (NK_RIA), otro recibió gel de AH/CMC y un grupo control. Los animales fueron sacrificados a los 7 ó 14 días, y se evaluó el número, severidad e histopatología de las AP. Tanto el NK-RIA como el AC/CMC disminuyeron el número (40% y 38% respectivamente) y severidad de las AP (p=0,001 y p=0,029 rerspectivamente) en relación al grupo control, sin diferencias estadísticas entre ellos (p=0,806). El grupo de NK-RIA presentó menos AP en órganos no manipulados durante la cirugía en relación a los otros 2 grupos. Ambos tratamientos presentaron menor grado de fibrosis que el control, sin embargo el grupo de NK-RIA tuvo menor inflamación (P=0,005) y proliferación vascular (P=0,047) que el AH/CMC. El NK-RIA tiene alta eficacia previendo la formación de AP, equiparable a la gel de AH/CMC.
The fibrinolytic activity play an important role in the peritoneal adhesions (PA) development. Its well known that of substance P decreased the fibrinolysis by binding the neurokinin-1 receptor, improving the PA formation. Lot of investigation have evaluated the efficacy in PA prevention of antagonist of these receptors, with very good result. To compare the effectivences of intraperitoneal treatment with a neurokin-1 receptor antagonist (NK-RIA) versus hyaluronic acid/carboxymethylcellulose (HA/CMC) gel, in peritoneal adhesion prevention in animal model. In 60 male Wistar rats, PA were induced, and then randomly assigned to 3 groups. A group treated with aprepitant (NK-RIA), a second group treated with HH/CMC and a control group. The animals were killed at 7 or 14 postoperative day, and the number, severity and histopathology of PA were evaluated. NK-RIA and HA/CMC decreased the number (40% and 38% respectively) and severity (p=0,001 and p=0,029 respectively) of PA when compare to control group. The NKRIA group had less PA in no manipulated organs in surgery that the others 2 groups. Both treatments presented less fibrosis that control, however the NK-RIA group presented less inflammation (p=0,005) and vascular proliferation (p=0,047) than HA/CMC group. The NK-RIA is as effective as HC/CMC in preventing PA.
Subject(s)
Animals , Rats , Receptors, Neurokinin-1/antagonists & inhibitors , Thrombolytic Therapy/methodsABSTRACT
Substance P is one of the most important neurotransmitter in the nervous system. It plays an important role in the pathological process of many diseases through combineing with its receptors, for example, neurokinin-1 receptor (NKIR). The antagonists of NK1R (NK1RA) that are widely used in recent clinical treatments can not only relieve deppression and anxiety, but also have good antiemetic effects on chemotherapy-induced nausea and vomiting. In this review, the relevant study results in this field in recent years are described.
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Objective To investigate the effect of budesonide on NK-1 receptor expression in airway smooth muscle cell (ASMC). Methods According to the random method,45 wistar rats were divided into three groups: asthmatic group, budesonide treatment group and control group. Aerosolize ovalbumin was used to make asthmatic rat model. Budesonide treatment group were given budesonide after inhaled ovalbumin. On day 21 .primary rat ASMC culture was conducted. The fourth cell passage and purified ASMC was collected for RT-PCR. The content of NK-1R was determined by real-time quantitative PCR. Data were expressed as mean±standard error (SE). The ANOVE Tukey test was carried out by using SPSS17.0 software and P＜0. 05 was considered significant. Results As compared with that of asthmatic group(1.1687±0.1356),NK-1R mRNA in therapy group( 1.0820 ±0. 1146) decreased significantly (P ＜0.05) ,but remained still higher than that of control group(1.034 7±0.2503) (P＜0. 05). Conclusion NK-1R may be involved in the pathogenesis of asthma. Budesonide may down-regulate the expression of the NK-1R mRNA in the airway smooth muscle cell, which may inhibit inflammation in asthmatic attacks.
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BACKGROUND AND OBJECTIVES: In airway tissues, the substance P has been suggested as the neurotransmitter in the afferent sensory nerve which responds to various irritants and that it may be involved in airway allergic reactions. Neurokinin 1 receptor exhibits preferential affinity for the substance P. In contrast to the substance P, neurokinin 1 receptor has not been examined at the protein level in nasal mucosa with allergic rhinitis. The purpose of this study was to investigate the localization and distribution of the neurokinin 1 receptor in the nasal mucosa of normal subjects and allergic rhinitis subjects. MATERIALS AND METHOD: Biopsy specimens were collected from 10 normal control subjects and 10 allergic rhinitis subjects and were immunostained for the neurokinin 1 receptor. Expressions of neurokinin 1 receptor were quantified through a light microscope. RESULTS: Neurokinin 1 receptor was localized at the epithelium, inflammatory cells, vascular endothelial cells, and glandular cells in the nasal mucosa of both normal subjects and allergic rhinitis subjects. When comparing the distributions of normal nasal mucosa and neurokinin 1 receptor, the neurokinin 1 receptor was significantly increased in the epithelial cell layer of allergic rhinitis, but there was no difference in the submucosa between two groups. CONCLUSION: These results show that neurokinin 1 receptor in the nasal epithelial cells may play an important role in the pathogenesis of hyper-reactivity in allergic rhinitis.
Subject(s)
Biopsy , Endothelial Cells , Epithelial Cells , Epithelium , Hypersensitivity , Irritants , Nasal Mucosa , Neurotransmitter Agents , Receptors, Neurokinin-1 , Rhinitis , Substance PABSTRACT
Objective To investigate the expression of neurokinin 1 receptor (NK 1R) in the biopsy specimens of colonic mucosa in patients with ulcerative colitis (UC). The relation between the expression of NK 1R and clinical severity of UC was also evaluated. Methods UC tissues were obtained from 38 patients (23 males and 15 females) undergoing colonoscopy. Normal human colon tissues were obtained from 15 irritable bowel syndrome (IBS) patients (8 males and 7 females). Reverse transcription polymerase chain reaction (RT PCR), western blot and immunohistochemistry were used to determine the expression of NK 1R. Results NK 1R mRNA expression level was enhanced in mucosae of UC compared with that of IBS. The overexpression of NK 1R was related to the severity of UC. Western blot analysis revealed that the overexpression of NK 1R protein level existed in UC. Immunohistochemistry showed moderate to strong NK 1R immunoreactivity which was localized in mononuclear cells and lymphoid follicles of lamina propria and in the crypt surface, epithelium, lymphoid follicles, submucosal arterioles and myenteric plexus neurones in the colonic mucosa of UC. Conclusions In patients with UC, the overexpression of NK 1R may be involved in the pathophysiological change in the disease and may contribute to the disruption of neuropeptide loop balance and deterioration of clinical condition.
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Objective:To study the effect of substance P on sensation afferent of gastrointestinal tract and the corresponding mechanism. Methods:Forty SD rats were divided into 5 groups:control group,low dosage SP group(75 ng/kg),middle dosage SP group(150ng/kg), high dosage SP group(300 ng/kg)and spantideII+SP group.The electrophysiological method was used to record the change of spontaneous and gastric distention-induced afferent discharge of subdiaphragmatic vagus nerve in each group.Results:Intravenous SP (150 ng/kg,300 ng/kg)caused significantly increasing effect on the spontaneous afferent discharge(P