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Abstract］ AIM and METHODS:The recent work from our laboratory showed that ventral septal area (VSA) played a negative-regulatory central role in thermoregulation during endogenous pyrogen-induced fever. In order to further investigate the role of VSA in the antipyretic mechanism, we observed the effects of electrical stimulation of VSA on firing characteristics of thermosensitive neurons in preoptic anterior hypothalamus (POAH) by using extracellular microelectrode technique on 32 New Zealand white rabbits treated with interleukin-1 β (IL-1β) intracerebroventriculary (ICV). RESULTS:(1)Injection of IL-1β decreased discharging rate of warm-sensitive neurons in POAH. Electrical stimulation of VSA remarkably decreased thermosensitive coefficient of warm-sensitive neurons. (2)Injection of IL-1β caused increase in discharging rate of cold-sensitive neurons in POAH. Electrical stimulation of VSA remarkably increased thermosensitive coefficient of cold-sensitive neurons. CONCLUSTION:VSA may have an antipyretic effect through affecting the firing characteristics of thermosensitive neurons in POAH during IL-1β-induced fever.
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The primary action of corticotropin releasing hormone (CRH) is stimulation of the synthesis and release of adrenocorticotropic hormone and β-endorphin from the pituitary in response to stress. In addition, a number of studies indicate that CRH exerts other physiological actions within the central nervous system which are independent of the pituitary. These include increased body temperature and thermogenesis. However, the intracellular mechanism responsible for pyrogenic action of CRH is still unclear. The purpose of these studies was to determine whether or not cAMP was involved in the pyrogenic action of CRH in the rat. Intracerebroventricular (icv) microinjection of CRH (2.5 μg, 5.0 μg, 10 μg) caused increases in colonic temperature and hypothalamus cAMP level in conscious rats. The pyrogenic effects of CRH were abolished or markedly inhibited by prior injection (icv) of an adenylate cyclase inhibitor, 2，，3，-dideoxyadenosine (DDA, 30 μg) or an inhibitor of cAMP-dependent protein kinase, adenosine-3，，5，-(cyclic) monophosphorothionate (Rp-cAMPs, 15 μg). This is the first report demonstrating the pyrogenic effcet of centrally administration of CRH on the rat via the cAMP-mediated protein kinase signal transduction pathway.
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AIM and METHODS:To investigate the effect of electrical stimulation of VSA on the firing of thermosensitive neurons in preoptic anterior hypothalamus (POAH), the firing rate of thermosensitive neurons in POAH of 20 New Zealand white rabbits was recorded by using extracellular microelectrode techinque. RESULTS:(1)Electrical stimulation of ventral septal area (VSA) caused a significant increase in firing rate of warm-sensitive neurons in the preoptic area of the anterior hypothalamus(POAH).(2) The firing rate of cold-sensitive neurons was decreased remarkably in the POAH by electrical stimulation of VSA. CONCLUSION:VSA may play a controlling role in the thermoregulation through altering the firing rate of thermosensitive neurons in the POAH.
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α-MSH is an endogenous neuropetide that is effective of all categories of expreimental inflammation. The mechanisms underlying the anti-inflammatory influence of α-MSH are reviewed in the article. α-MSH suppresses inflammation in the CNS and periphery by downregulating the activation of NF-κB, then inhibiting production of proinflammatory cytokines, nitric oxide, chemokines and adhension molecules, and increasing synthesis of anti-inflammatory cytokines. α-MSH is useful in the treatment of many pathological situations in humans.
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AIM: The present study was undertaken to explore the effects of ?-MSH on partial biological activities of LPS. METHODS:Colorimetric method was used for the measurement of hydrogen peroxide(H_2O_2) production in mouse peritoneal macrophages, the apoptosis of polymorphonuclear leukocytes(PMNs) and the binding of LPS to monocytes were studied with flow cytometry. RESULTS: It was found that LPS strongly stimulated macrophages to release H_2O_2. When macrophages were cultured with ?-MSH in the presence of LPS, the H_2O_2 release was markedly suppressed (P0.05). In the presence of LPS, however, ?-MSH significantly promoted the apoptosis of PMNs (P
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AIM: To study the influence of glycine(GLY) on lipopolysaccharide-binding protein(LBP) mRNA expression induced by LPS. METHODS: The level of LBP mRNA expression in liver tissues of rats was examined by RT-PCR,and the effects of glycine on LBP mRNA expression in liver tissues of rats induced by LPS were investigated. RESULTS: The level of LBP mRNA expression in hepatic tissue of rats in the LPS group was significantly higher than that in the control group( P
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AIM: To investigate intracellular free calcium ([Ca 2+ ]i ) alterations in hypothalamus of febrile rabbits induced by endotoxin (ET), and compare with the effect of ET and IL-1? on [Ca 2+ ]i in hypothalamic neurocytes from normothermia rabbits. METHOD: The concentration of [Ca 2+ ]i was determined by using spectrofluorometer and fluorescent Ca 2+ probe fura-2 /Am. RESULTS: 1. A minute dose of ET (2 ng/mL) induced a significant rise in [Ca 2+ ]i in hypothalamic neurocytes from normothermia rabbits. The rise in [Ca 2+ ]i in hypothalamic neurocytes from febrile rabbits induced by intravenous injection of ET was also observed. 2. In hypothalamic neurocytes from normotheria rabbits, IL-1? failed to affect [Ca 2+ ]i at concentrations of 100, 500, 1 000 ng/mL, respectively. CONCLUSION:The action site of low concentration of calcium that plays a regulatory role during fever seems unlikely to be in cytosolic compartment of hypothalamic neurons. The change of [Ca 2+ ]i in hypothalamic neurocytes by ET can not be considered the direct effect of IL-1?.
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AIM: To explore effects of glycine and polymyxin B mixture (Gly/PMB) on endotoxin-induced acute phase response in vivo . METHODS: Model of acute phase response was reconstructed by endotoxin (ET) in rabbits. Specimens of blood were collected at 1 hour after the highest body temperature. Leukocyte count, serum C-reactive protein and trace element were also detected. RESULTS: Pretreatment of half-dose Gly/PMB significantly inhibited acute phase response induced by ET ( P 0.05). CONCLUSION: These results suggested that glycine enhanced the inhibitory effect of polymyxin B on ET-induced acute phase response. The advantage of glycine and polymyxin B mixture was decreasing dosage and side effects of polymyxin B. [
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AIM: To investigate the mechanisms by which siduqing, a Chinese medicine, protects against lipopolysaccharide (LPS)-induced acute renal dysfunction. METHODS: Mice were divided randomly into control, LPS, siduqing treatment and siduqing groups, and treated intragastrically with siduqing at a dose of (1 000) g/L (0.2 (mL/10 g) body weight) or distilled water (0.2 (mL/10) g body weight) twice a day for 3 days, LPS (30 mg/kg) or normal saline was injected intraperitoneally on day 3, followed by intragastrical administration with siduqing at a dose of (1 000) g/L (0.2 (mL/10 g) body weight) or distilled water (0.2 (mL/10 g) body weight). Blood was collected for determining urea nitrogen (BUN) and creatinine (Cr) contents, renal tissue for examining superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. In addition, electron microscopy was used to examine the ultrastructure changes in kidney, and RT-PCR was performed to detect renal intercellular adhesion molecule-1 (ICAM-1) mRNA expression. RESULTS: LPS significantly increased serum urea nitrogen (BUN) and creatinine (Cr) contents, and produced an obvious pathological change in renal ultrastructure, which were significantly attenuated by siduqing treatment. Moreover, siduqing treatment increased renal SOD activity, also markedly suppressed an increase in renal MDA production and ICAM-1 mRNA expression induced by LPS. CONCLUSION: These results suggest that siduqing protects against LPS-induced acute renal injury through inhibiting ICAM-1 mRNA expression, enhancing renal SOD activity and attenuating oxidant stress.
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AIM: To investigate whether glycine receptor is involved in the protection of glycine against(anoxia/reoxygenation) injury in cardiomyocytes by detecting oxygen free radical metabolism,apoptosis and intracellular calcium overload.METHODS: The neonatal rat cardiomyocytes were cultured and exposed to anoxia and reoxygenation((A/R)) in the presence of glycine receptor antagonist,glycine or in free chloride buffer.The superoxide dismutase(SOD) activity,the contents of malondialdehyde(MDA) and nitric oxide(NO),the intracellular free calcium concentration and the apoptotic rate in the cardiomyocytes were determined.RESULTS: SOD activity and NO content in cardiomyocytes were lower,but MDA content,intracellular free calcium concentration and apoptotic rate in cardiomyocytes were higher in A/R group than those in control.Pretreatment with glycine inhibited the above changes caused by A/R,which was reversed by strychnine treatment and in the free chloride medium.CONCLUSIONS: Glycine inhibits free radical production,attenuates calcium overload,decreases apoptotic rate and increases SOD activity and NO release in cardiomyocytes exposed to(A/R).These findings suggest that glycine exerts a protective effect against A/R injury via glycine receptor and glycine protects the neonatal rat cardiomycytes from A/R-induced injury in a chloride-dependent manner.
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AIM and METHODS: To investigate the functional connection between the preoptic anterior hypothalamus (POAH) and the ventral septal area (VSA) in fever mechanism, the firing rates of thermosensitive neurons in the VSA of 26 New Zealand white rabbits were recorded using extracellular microelectrode technique. RESULTS: The firing rates in both types of thermosensitive neurons in the VSA had no significant changes after intracerebroventricular (icv) injection of artificial cerebrospinal fluid(ACSF). When interleukin-1β (IL-1β) was given (icv), the firing rate of the warm-sensitive neurons was increased significantly and that of the cold-sensitive neurons was decreased remarkably. The effects of IL-1β on the changes of firing rate in thermosensitive neurons of the VSA were reversed by electrical stimulation of the POAH. CONCLUSION: The roles of positive and negative thermoregulatory centers in the interaction between the POAH and VSA are closely linked during endogenous pyrogen induced fever.
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AIM: To investigate the protective effect of Siduqing, a Chinese medicine, on LPS-induced myocardium injury in mice and its mechanisms. METHODS: Mice were divided into 4 group: control, LPS, Siduqing treatment and Siduqing group, and administered intragastrically with Siduqing decoction or distilled water (0 2 mL/10 g) twice a day for 3 days, two hours after Chinese herbal medicine treatment on day 3, LPS (30 mg/kg) or normal saline was injected intraperitoneally. The serum creatine kinase (CK) and myocardial superoxide dismutase (SOD) activities were determined, and myocardial tumor necrosis factor ? (TNF?) and malondialdehyde (MDA) contents were also detected. In addition, the histological changes and ultrastructure of heart were examined. RESULTS: Histological examination showed edema in myocardium and architectural disarray at 12, 24 h after LPS injection, mitochondrial swelling, condensation and margination of chromatin, irregular nuclear envelope and loss of contractile filaments at 24 h post LPS administration, while Siduqing treatment attenuated the above pathological changes of myocardium. CK activity in serum and myocardial TNF? content were higher in LPS group than control and Siduqing treatment group. Myocardial SOD activity in siduqing treatment group was higher than that in LPS group, but there was no difference in myocardial MDA content between control, LPS and Siduqing treatment group. CONCLUSION: These data suggest that Siduqing protects myocardium against LPS- induced injury via inhibiting myocardial TNF? production.
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The levels of cyclic AMP and prostaglandin E (PGE) in the brain are raised in many kinds of fever induced by various pyrogens, we also know when the ratio of Na~+/Ca~(++) is changed in the brain, the body temperature changes. So it is suggested that cAMP, PGE and the ratio of Na~+/Ca~(++) are major central mediums in febril response. It is not clear what relationship is among these three factors and what are their roles respectively in the fever mechanism? It must be very helpful for the development of fever study if we can have them correctly answered. In this paper, we change the Na~+/Ca~(++) ratio by intraventricular perfusion with EGTA or CaCl_2, and observed the temperature response, levels of cAMP and PGE_2 in c.s.f. It is found that there was a positive correlation between cAMP and the body temperature(r=0.9913, P0.05). EGTA can raise body temperature. But CaCl_2 pretreatmentd could lower the EGTA fever.
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0.05) after non-fever limit (non-FL) dose and FL dose endotoxin (ET) was intravenously injected into rabbits. The increase of PGE_2 in CSF was not limited during the occurrence of ET FL. 2. Intracerebroventricular injection (ICV) of different dose of PGE_2 into rabbits induced dose-dependent fever, but there was no more rise in body temperature when the febrile response had reached a certain height. This is termed "PGE FL". 3. The concentration of cyclic adenosine-3′, 5′-monophosphate (cAMP)in CSF paralleled the fluctuation of temperature (r=0.9906, P
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In order to determine further whether cAMP and PGE takes part in the mechanism of EGTA-induced fever in the present experiment with 40 New Zealand rab bits, the influence of intravenous infusion of sodium salicylate (SS) on the febrile response and the rise of cAMP and PGE_2 concentration in c.s.f. produced by intraventricular perfusion of EGTA were observed. The results showed that intravenous infusion of SS (9.6?M/min. following an initial dose of 1.25mM) could inhibit the rise of PGE_2 concentration in c.s.f. (P0.05) after 0.6 mM EGTA was perfused into lateral cerebroventricle. The concentration of cAMP in c.s.f. was correlated apparently positively with the febrile response in EGTA-induced fever (r=0.9839, P
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AIM:To investigate the effect of dimethyl sulfoxide on endotoxin -induced fever in rabbits. METHODS:Test substances were administered intravenously into a marginal ear vein. Temperature responses were measured using rectal thermistor probes. RESULTS:Endotoxin (0.4 ?g/kg) stimulated a biphasic rise in colonic temperature. Pretreatment with dimethyl sulfoxide significantly attenuated the biphasic febrile response to endotoxin (0.4 ?g/kg) of conscious rabbits in a dose-dependent manner. Rabbits treated with dimethyl sulfoxide 10 min after injection of endotoxin developed fever, which was significantly milder compared with rabbits treated with an equal volume of normal saline. No significant differences were found between thermal response index of rabbits injected with dimethyl sulfoxide and those with normal saline. CONCLUSION:Dimethyl sulfoxide inhibit endotoxin-induced fever in rabbits.
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AIM and METHODS: To investigate the effect of electrical stimulation of VSA on the firing of thermosensitive neurons in preoptic anterior hypothalamus (POAH), the firing rate of thermosensitive neurons in POAH of 20 New Zealand white rabbits was recorded by using extracellular microelectrode techinque. RESULTS: (1)Electrical stimulation of ventral septal area (VSA) caused a significant increase in firing rate of warm-sensitive neurons in the preoptic area of the anterior hypothalamus(POAH).(2) The firing rate of cold-sensitive neurons was decreased remarkably in the POAH by electrical stimulation of VSA. CONCLUSION: VSA may play a controlling role in the thermoregulation through altering the firing rate of thermosensitive neurons in the POAH .
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AIM: To study the expression of glycine receptor (GlyR) in adult rat cardiac tissue and cultured cardiomyocytes from neonatal rat hearts. METHODS: Total RNA and membrane protein were extracted from cardiac tissue of adult rats and primary cultured cardiomyocytes from neonatal rat hearts, ?1 and ? subunits mRNA and protein of GlyR were detected with the method of reverse transcription nest DNA polymerase chain reaction (RT-PCR) and Western blotting. RESULTS: The mRNA and protein expression of ? subunit were identified in the adult rat heart tissue and cultured cardiomyocytes, similar to the sequence and immunogenicity generated from GlyR ? subunit of the rat spinal cord; for ?1 subunit, mRNA was found in only cultured cardiomyocytes. CONCLUSION: These data demonstrate that adult rat cardiac tissue and cultured cardiomyocytes from neonatal rat hearts express mRNA and protein of GlyR subunits similar to the GlyR that expresses in the spinal cord, suggesting that GlyR exists in the membrane of the rat cardiomyocytes.
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AIM: To investigate the differences of Alzheimer's disease(AD)-related parameters in the SAM-P/8, the SAM-R/1 and the Kunming mice.METHODS: The changes of ethology, neurobiochemistry (true choline esterase, TchE), ultrastructure and gene expression(gene chips) were determined in mice of three groups: SAM-P/8 mice (n=14), SAM-R/1 mice (n=14) and Kunming mice (n=14), which were 6 months old[weight(20?5)g].RESULTS: The SAM-P/8 mice had the inabilities of learning and memory compared with the SAM-R/1 mice and the Kunming mice (P
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AIM: To observe the influence of glycine on intracellular free calcium, the concentration of tumor necrosis factor-? and the survival rate of myocardial cells during hypoxia/reoxygenation (H/R). METHODS: The simulated model of myocardial ischemia-reperfusion with the primary cultured cardiomyocytes of neonatal rats was established, and the cultured cardiomyocytes were divided into seven groups, control group, hypoxia/reoxygenation group, glycine (0.5 mmol/L) plus hypoxia/reoxygenation group, glycine (1.0 mmol/L) plus hypoxia/reoxygenation group, glycine (2.0 mmol/L) plus hypoxia/reoxygenation group, glycine (4.0 mmol/L) plus hypoxia/reoxygenation group, 4.0 mmol/L glycine group. RESULTS: Within certain concentration (0.5-2.0 mmol/L), the glycine could inhibit the calcium overload resulting from hypoxia/reoxygenation injury in cells in a dose-dependent manner with the optimal inhibitory effect at 2.0 mmol/L. Glycine inhibited the secretion of tumor necrosis factor-? from myocardial cells and increased the survival rate of myocardial cells. CONCLUSION: Glycine has a protective effect on hypoxia/reoxygenation myocardial cells, which may be related to inhibiting calcium overload and decreasing the production of tumor necrosis factor-?.