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Objective To evaluate the effects of dexmedetomidine on the expression of c-fos in hippocampus and dentate gyrus in a rat model of endotoxic shock.Methods Thirty-five pathogen-free healthy male Sprague-Dawley rats,aged 3-4 months,weighing 250-300 g,were divided into 5 groups (n =7 each) using a random number table:normal saline group (group NS),dexmedetomidine group (group D),endotoxic shock group (group ES),low-dose dexmedetomidine plus lipopolysaccharide (LPS) group (group LD) and high-dose dexmedetomidine plus LPS group (group HD).Dexmedetomidine 0.5 μg/kg was injected via the tail vein in D and LD groups,and dexmedetomidine 4.5 μg/kg was given in group HD.Normal saline 0.5 ml/kg was injected in NS and ES groups,5 min later normal saline 0.5 ml/kg was injected in NS and D groups and LPS 5 mg/kg was injected in the other groups,and the injection time was 10 min in all groups.Rats were sacrificed at 6 h after LPS injection,brains were removed,and the hippocampus and dentate gyrus were isolated for detection of the expression of c-fos by immunohistochemistry.Results Compared with group NS or group D,the expression of c-fos in the hippocampus and dentate gyrus was significantly up-regulated in group ES (P＜0.05).Compared with group LPS,the expression of c-fos in the hippocampus and dentate gyrus was significantly down-regulated in LD and HD groups (P＜0.05).Compared with group LD,the expression of c-fos in hippocampal CA1 and CA3 areas was significantly down-regulated in group HD (P＜0.05).Conclusion The neuroprotective mechanism of dexmedetomidine is related to inhibiting the up-regulated expression of c-fos in the hippocampus and dentate gyrus in a rat model of endotoxic shock.
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Objective To observe the effect of Rhy-SLN on the proliferation of rat vascular smooth muscle cells (VSMC) induced by TGF-β1, and explore the mechanism. Methods The primary culture of rat thoracic aortic vascular smooth muscle cells was studied by tissue block culture method. The cells were divided into the control group, TGF-β1 group, TGF-β1+ the high, medium and low dosage groups of Rhy-SLN. In addition to the control group, the cells of the other groups were involved in the intervention of TGF-β1 of 20 g/L, and the high, medium and low dosage groups of Rhy-SLN cells were involved in the intervention of 25, 50, 100 mg/L of the hook teng solid lipid nanoparticles. After 24 hours of culture, MTT assay was used to detect cell proliferation inhibition rate in each group, and the cell cycle was detected by flow cytometry. The expression of c-myc and c-Fos protein in each group was detected by Western blot method. Results Compared with the TGF-β1 group, the absorbance value (0.457 ± 0.046 vs. 0.975 ± 0.049) of TGF-β1+ rhy-sln high dose group significantly decreased (P<0.01); the number of S phase cells (15.87% ± 2.47%, 15.23% ± 1.69%, 17.02% ± 2.87% vs.38.58% ± 2.68%)of TGF-β1+rhy-sln in each dose group significantly decreased(P<0.01);The c-myc(48.65 ±3.65,50.69 ± 4.16,55.29 ± 3.67 vs.68.21 ± 3.25)and c-Fos(38.78 ± 4.25,43.56 ± 3.69,46.58 ± 3.57 vs.66.54 ± 4.09) of the TGF-β1+ rhy-sln each dose group significantly decreased (P<0.01). Conclusions The Rhy-SLN can inhibit the proliferation of VSMC in rats induced by TGF-β1.Its mechanism is related to the conversion of G0/G1 phase to the S phase and the expression of the reduction of c-myc and c-fos protein.
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Objective To evaluate the effect of intrathecal dexmedetomidine on expression of sub-stance P (SP) and c-fos in the spinal dorsal horns of rats with visceral pain. Methods Thirty-two clean-grade healthy adult male Sprague-Dawley rats, weighing 250-300 g, were divided into 4 groups ( n=8 each) using a random number table method: control group (C group), visceral pain group (VP group), dexmedetomidine group (D group) and dexmedetomidine plus atipamezole group (DA group). VP, D and DA groups received intraperitoneal injection of 0. 9％ acetic acid 10 ml∕kg to establish the model of visceral pain, while group C received the equal volume of normal saline instead. At 10 min before the model was es-tablished, dexmedetomidine 20 μl (1μg∕kg) and dexmedetomidine 1μg∕kg plus atipamezole 1μg∕kg (20μl) were intrathecally injected in D and DA groups, respectively, and the equal volume of normal saline 20μl was given instead in C and VP groups. Visceral pain index ( VPI) was recorded at 1 h after intraperito-neal injection, and then rats were sacrificed, and the dorsal horns of the spinal cord ( L4-6 ) were removed for determination of the expression of SP and c-fos by immunohistochemistry. Results Compared with group C, VPI was significantly increased, and the expression of SP and c-fos was up-regulated in VP, D and DA groups (P<0. 05). Compared with group VP, VPI was significantly decreased, and the expression of SP and c-fos was down-regulated in D and DA groups (P<0. 05). Compared with group D, VPI was signifi-cantly increased, and the expression of SP and c-fos was up-regulated in group DA ( P<0. 05) . Conclusion Intrathecal dexmedetomidine reduces the visceral pain through inhibiting the expression of SP and c-fos in the spinal dorsal horns, which is related to the α2-adrenergic receptor in spinal dorsal horns of rats.
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Objective To evaluate the changes in the expression of c-fos protein in the spinal cord in a rat model of oxycodone dependence or withdrawal response.Methods Thirty SPF adult male Sprague-Dawley rats,aged 6-8 weeks,weighing 180-220 g,were divided into 3 groups (n=10 each) using a random number table method:normal saline group (group NS),oxycodone dependence group (group OD),and oxycodone withdrawal group (group OW).In OD and OW groups,oxycodone was injected subcutaneously in back,5 days in total,with the dose of 2,3,4,5 and 6 mg/kg in turn,3 times a day (8:00/15:00/22:00).The equal volume of normal saline was given instead in group NS.The mechanical paw withdrawal threshold was measured at 3 days before administration and 30 min after the last administration every day.The oxycodone withdrawal was induced by intraperitoneal injection of naloxone 4 mg/kg at 8 h after the last administration of oxycodone on 5th day in group OW.The withdrawal response scores and range of weight changes were recorded within 15 min after giving naloxone or normal saline in NS and OW groups.Spinal cord tissues were collected at 1 h after the last administration on 5th day in group OD and at 1 h after giving normal saline or naloxone on 5th day in NS and OW groups for determination of the expression of c-fos protein by Western blot.Results Compared with group NS,the mechanical paw withdrawal threshold was significantly increased on 1 and 2 days after administration,and the expression of c-fos protein in the spinal cord was up-regulated in OD and OW groups,and withdrawal response scores were significantly increased,and the range of weight change was increased in group OW (P＜0.05).The expression of c-fos protein was significantly down-regulated in group OW as compared with group OD (P＜0.05).Conclusion Oxycodone dependence or withdrawal response may be related to the expression of c-fos protein in the spinal cord of rats,and the expression is up-regulated during oxycodone dependence,while down-regulated during oxycodone withdrawal.
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Objective To explore the role of pregabalin on the expression of c-fos in spinal dorsal horn of the rat with neuropathic pain.Methods Thirty Wister rats (male) were divided into shamoperated group,model group and pregabalin group,with 10 cases in each group.The effect of the pregabalin on the heat pain threshold and expression of c-fos in spinal dorsal horn of the rat with neuropathic pain were observed.Results The heat pain threshold in model group at 3rd,4th,5th,6th,7th,10th and 14th day after operation was significantly lower than that in sham-operated group and pregabalin group at same time (P ＜ 0.05).The heat pain threshold in pregabalin group was lower than that in sham-operated group from 2nd day after operation,but there was no significant difference (P ＞0.05).At the 14th day after operation,the number of Fos-like-immunoreactivity (FLI) positive cells in sham-operated group,model group and pregabalin group was (16.4 ± 0.6),(66.7 ± 3.3) and (22.8 ± 1.5)cases,and the number of FLI positive cells in model group was significantly higher than that in shamoperated group and pregabalin group (P ＜ 0.05).Conclusions Pregabalin has analgesic activity on rat with neuropathic pain.Pregabalin activates spinal cord glial cells raisedby the injured peripheral nerve and infection,and also reduces the noxious stimulation of afferent pain to spinal dorsal horn neurons.
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Objective@#To investigate the effect of restraint stress on masseter mechanical hyperalgesia and the activity of neurons and astrocytes in the spinal trigeminal nucleus caudalis (Vc).@*Methods@#The animals were randomly divided into the control group, 1-, 3-, 5-, 7-, 9-, 11-and 14-day stress groups, with 10 rats in each group. The body weight increase and behavior tests were used to testify the animal model. The mechanical sensitivity of masseter of the rat before and after the stress was measured with Von Frey filaments. Histological examinations were used to evaluate the expression of neuronal c-fos and astrocytic glial fibrillary acidic protein (GFAP).@*Results@#Restraint stress resulted in remarkable mechanical allodynia in the masseter muscle. The head withdrawal threshold was significantly lower in the 7-, 9-, 11-and 14-day stress groups ([0.071±0.011], [0.059±0.020], [0.052±0.011], [0.033±0.011] N) than that in the control group ([0.120±0.025] N) (P<0.05). Compared to the control group, the rats in the 1-day stress group showed a significant increase of c-fos in neurons of the Vc and then declined to normal level after 1 week gradually. The GFAP expression in astrocytes of the Vc was significantly increased in the 7-, 9-, 11-and 14-day stress groups (4.3±1.0, 4.5±0.6, 4.6±0.5, 4.8±1.3) compared with the control group (2.0±0.8) (P<0.05).@*Conclusions@#Chronic restraint stress could lower the threshold of mechanical allodynia in the masseter muscle and activate the neurons and astrocytes in Vc. The activation of neurons and astrocytes plays an important role in the masseter hyperalgesia induced by restraint stress in rats.
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Objective To investigate the effect of electro‐acupuncture combined with sevoflurane anesthesia on the regula‐tion of acute stress response in docked tails rats .Methods Fifty male SD rats weighing 280-320 g were randomlsy divided into 5 groups(n=10 each):normal group (group Ⅰ) ,model group (group Ⅱ) ,sevoflurane group (group Ⅲ) ,sevoflurane inhalation com‐bined with body acupuncture group (group Ⅳ) and sevoflurane combined with auricular acupuncture group (group Ⅴ) .The groupⅠwas placed in a glass box containing mixture gas with oxygenflow of 30% (flow 2 L/min) without treatment ,the group Ⅱafter docking tail was placed in a glass box containing mixture gas with oxygenflow of 30% (flow 2 L/min) ,the group Ⅲ ,Ⅳ and Ⅴwere placed in the 2% sevoflurane anesthesia box (flow 2 L/min) ,the group Ⅳ was given continuous stimulation at Zusanli (stimu‐lation parameters :3 V ,3 Hz ,2 ms) for 30 min per time ,4 times at intervals of 30 min ,the groupⅤ was given the stimulation at Er‐jian with the same stimulation parameters as the groupⅣ .Rats in each group were killed after treatment and the blood at broken neck was collected for measuring serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels by ELISA .The c‐fos protein expression level in hypothalamic tissue was detected by Western blot .Results Compared with the group Ⅰ ,serum ACTH ,CORT levels ,hypothalamic expression of c‐fos protein in the group Ⅱwere significantly increased (P0 .05);the ACTH level in the groupⅤ was significantly decreased compared with the groupⅢ(P<0 .05) and the CORT level in the group Ⅴ was also decreased when compared with the group Ⅳ(P<0 .05) .The c‐fos expression in the groupⅢ ,Ⅳ and Ⅴwere decreased compared with the groupⅡ (P<0 .05) ,there were significant difference among the group Ⅲ ,ⅣandⅤ(P<0 .05) .Conclusion In the treatment of sevoflurane inhalation anesthe‐sia combined with compound electrostimulation at Erjian ,its effect on stress response is superior to simple sevoflurane treatment and sevoflurane combined with compound electrostimulation at Zusanli .The regulation mechanism of electro‐acupuncture combined with inhalation general anesthesia on stress may be related with hypothalamus regulating paraventricular nucleus c‐fos protein se‐cretion and affecting the HPA axis .
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Objective To evaluate the effect of dezocine on the c-fos expression in neurons in the midbrain periaqueductal gray in a rat model of incisional pain.Methods Thirty-six pathogen-free healthy adult male Wistar rats,weighing 250-300 g,were divided into 3 groups (n =12 each) using a random number table:control group (group C),incisional pain group (group I) and dezocine group (group D).A 1 cm longitudinal incision was made through skin,fascia and muscle of the plantar aspect of the right hind paw in sevoflurane-anesthetized rats.In group C,the rats were only anesthetized and underwent no operation.In group I,0.9％ sodium chloride solution 2 ml was injected via the caudal vein at 15 min before the model was established.In group D,dezocine 1 mg/kg (diluted to 2 ml in 0.9％ sodium chloride solution) was injected via the caudal vein at 15 min before the model was established.At 24 h before operation (T0) and 2,6 and 24 h after operation (T1-3),the mechanical paw withdrawal threshold (MWT) and cumulative pain score were measured.After measurement of the pain threshold at T3,the whole brain was removed for determination of the c-fos expression in neurons in the midbrain periaqueductal gray by immunohistochemistry.Results Compared with group C,the MWT was significantly decreased,cumulative pain scores were increased,and the expression of c-fos in neurons in the midbrain periaqueductal gray was upregulated at T1-3 in I and D groups (P＜0.05).Compared with group I,the MWT was significantly increased,the cumulative pain score was decreased,and the expression of c-fos protein in neurons in the midbrain periaqueductal gray was down-regulated at T1.3 in group D (P＜0.05).Conclusion Dezocine mitigates incisional pain through inhibiting the expression of c-fos in neurons in the midbrain periaqueductal gray of rats.
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Objective To evaluate the effect of dexmedetomidine on the expression of c-fos protein in the dorsal root ganglion neurons in a rat model of neuropathic pain (NP).Methods Seventy-two adult male SpragueDawley rats,weighing 180-240 g,were randomly divided into 3 groups (n =24 each) using a random number table:sham operation group (group S),group NP,and dexmedetomidine group (group Dex).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.The right sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread in NP and Dex groups.In group Dex,dexmedetomidine 50μg/kg was injected intraperitoneally once a day starting from the end of operation until the animals were sacrificed.The equal volume of normal saline was given instead of dexmedetomidine in S and NP groups.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before ligation (T0,baseline) and 3,7 and 14 days after ligation (T1-3).Eight animals were sacrificed after measurement of pain threshold at T13 and the dorsal root ganglions of the lumbar segments (L44) were removed for detection of c-fos expression (by immuno-histochemistry).Results Compared with group S,MWT was significantly decreased,TWL was shortened,and the expression of c-fos protein was up-regulated at T1-3 in NP and Dex groups.Compared with NP group,MWT was significantly increased,TWL was prolonged,and the expression of c-fos protein was down-regulated at T1-3 in Dex group.Conclusion Dexmedetomidine can inhibit upregulation of c-fos protein expression,thus attenuating NP in rats.
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Objective To evaluate the effects of ischemic postconditioning (IPO) on c-fos protein expression during renal ischemia-reperfusion (I/R) in rats.Methods Seventy-five adult male Sprague-Dawley rats,aged 8-12 weeks,weighing 200-250 g,were randomly allocated into 3 groups (n =25 each) using a random number table:sham operation group (group S),I/R group and IPO group.Renal I/R injury was induced by clamping the bilateral renal pedicles for 1 h followed by 24 h of reperfusion in I/R and IPO groups.Five animals were sacrificed at 1,3,6,12 and 24 h of reperfusion and the left kidneys were removed for microscopic examination and for determination of the expression of c-fos protein by immunohistochemistry.Results Compared with S group,the expression of c-fos protein was significantly up-regulated at each time point during reperfusion in I/R and IPO groups.Compared with I/R group,the expression of c-fos protein was significantly down-regulated at each time point during reperfusion in group IPO.The pathologic changes were significantly attenuated in group IPO as compared with group I/R.Conclusion The mechanism by which IPO attenuates renal I/R injury is related to down-regulation of c-fos protein expression in the renal tissues of rats.
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Objective To evaluate the effects of dexmedetomidine on the expression of neuronal nitric oxide synthase (nNOS) and c-fos in the lcuos cruleus (LC) in a rat model of endotoxic shock.Methods Twentyeight male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were randomly divided into 4 groups (n =7 each):control group (group C),endotoxic shock induced by lipopolysaccharide (LPS) group (group L),lowdose dexmedetomidine group (groupLD) and high-dose dexmedetomidine group (group HD).Normal saline 0.5 ml/kg was injected via the tail vein in C and L groups.Dexmedetomidine 0.5 and 4.5μg/kg were injected via the tail vein in group LD and group HD,respectively.Normal saline 0.5 ml/kg was injected via the tail vein 10 min later in C,while LPS 5 mg/kg was injected intravenously 10 min later in the other groups.The rats were sacrificed and their brains were removed for determination of brain water content,the number of nNOS and c-fos positive cells and expression of nNOS and c-fos in the LC by immuno-histochemistry.Results Compared with group C,the brain water content was significantly increased,the number of nNOS and c-fos positive cells in the LC was enlarged,and the expression of nNOS and c-fos in the LC was up-regulated in group L (P ＜ 0.05).The brain water content was significantly lower,the number of nNOS and c-fos positive cells in the LC was smaller,and the expression of nNOS and c-fos in the LC was lower in LD and HD groups than in group L (P ＜ 0.05).The number of nNOS and c-fos positive cells in the LC was significantly smaller,and the expression of nNOS and c-fos in the LC was lower in HD group than in group LD (P ＜ 0.05).Conclusion Dexmedetomidine can down-regulate the expression of nNOS and c-fos in the LC,which may be one of brain-protective mechanisms of dexmedetomidine in a rat model of endotoxic shock.
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Objective To evaluate the effects of dexmedetomidine on the activity of cAMP response element binding protein (CREB) and c-fos in the spinal dorsal horn in a rat model of neuropathic pain.Methods Fifty-four adult male Wistar rats,aged 6-8 weeks,weighing 180-220 g,were randomly divided into 3 groups (n =18 each):sham operation group (group S),chronic neuropathic pain group (group C) and dexmedetomidine group (group D).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.The sciatic nerve was exposed and 4 ligatures were placed on the right sciatic nerve at 1 mm intervals with 4-0 silk thread in C and D groups.In group D,dexmedetomidine 50 μg/kg was injected intraperitoneally once a day starting from the end of operation until 1 day before the animals were sacrificed,while the equal volme of normal saline was injected instead of dexmedetomidine in S and C groups.Paw withdrawal threshold to mechanical stimulation with yon Frey filament (MWT) and paw withdrawal latency to thermal stimulation (TWL) were measured on 1 day before operation and 3,7 and 14 days after operation.The animals were sacrificed after measurement of MWT and TWL.Their lumbar segments (L4-6) of the spinal cord were removed for measurement of the expression of phosphorylated CREB (pCREB) and c-fos by immunohistochemistry.Results Compared with group S,MWT was significantly decreased,TWL was shortened,and the expression of pCREB and c-fos was up-regulated on 3,7 and 14 days after operation in C and D groups (P ＜ 0.05).Compared with group C,MWT was significantly increased,TWL was prolonged,and the expression of pCREB and c-fos was down-regulated on 3,7 and 14 days after operation in group D (P ＜ 0.05).MWT was significantly lower,and TWL was shorter on 3,7 and 14 days after operation than on 1 day before operation in C and D groups (P ＜ 0.05).MWT was significantly lower,TWL was shorter,and the expression of pCREB and c-fos was higher on 7 and 14 days after operation than on 3 days after operation in C and D groups (P ＜ 0.05).MWT was significantly higher,TWL was longer,and the expression of pCREB and c-fos was lower on 14 days after operation than on 7 days after operation in C and D groups (P ＜ 0.05).Conclusion The mechanism by which dexmedetomidine reduces neuropathic pain is related to inhibition of the activity of CREB and c-fos in the spinal dorsal horn of rats.
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Objective To observe the changes of c-fos protein expression in brain and beta-endorphin (β-EP) level in blood plasma in rats with diffuse brain injury (DBI) and secondary brain insult (SBI) after intraperitoneal injection of naloxone hydrochloride, and explore the role of c-fos and β-EP in development of SBI in rats. Methods Seventy health male SD rats were enrolled in the present study and randomly divided into group A (intraperitoneally injected with 0.9% saline after DBI and SBI model was reproduced), group B (injected intraperitoneally with 1.0mg/kg naloxone hydrochloride after DBI and SBI model was reproduced), and group C (intraperitoneally injected with 1.0mg/kg naloxone hydrochloride after DBI and before SBI model was reproduced). The animals were sacrificed 3, 24 and 48 hours after injury, and the number of c-fos positive cells in brain and content of β-EP in blood plasma were determined by immunohistochemistry and radioimmunoassay respectively, the water content and number of injured neurons in brain tissue were measured by pathomorphological observation of the brain tissue. Results No significant difference was observed between group B and C for all the detection parameters. In group B and C, the water content in brain tissue at 3h and 24h was found to be decreased, while the number of injured neurons at 24h and 48h increased, number of c-fos positive cells in brain at 3h, 24h and 48h decreased, and content of β-EP in blood plasma at 3h and 24h decreased when compared with group A(P<0.05). Conclusion Naloxone hydrochloride could decrease the c-fos expression in brain and β-EP level in blood plasma, alleviate the nerve injury, and protect neural function. The therapeutic effect of naloxone administered either after DBI and SBI or after DBI and before SBI was similar.
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Objective To observe the changes of c-fos protein expression in brain and beta-endorphin (β-EP) level in blood plasma in rats with diffuse brain injury (DBI) and secondary brain insult (SBI) after intraperitoneal injection of naloxone hydrochloride, and explore the role of c-fos and β-EP in development of SBI in rats. Methods Seventy health male SD rats were enrolled in the present study and randomly divided into group A (intraperitoneally injected with 0.9% saline after DBI and SBI model was reproduced), group B (injected intraperitoneally with 1.0mg/kg naloxone hydrochloride after DBI and SBI model was reproduced), and group C (intraperitoneally injected with 1.0mg/kg naloxone hydrochloride after DBI and before SBI model was reproduced). The animals were sacrificed 3, 24 and 48 hours after injury, and the number of c-fos positive cells in brain and content of β-EP in blood plasma were determined by immunohistochemistry and radioimmunoassay respectively, the water content and number of injured neurons in brain tissue were measured by pathomorphological observation of the brain tissue. Results No significant difference was observed between group B and C for all the detection parameters. In group B and C, the water content in brain tissue at 3h and 24h was found to be decreased, while the number of injured neurons at 24h and 48h increased, number of c-fos positive cells in brain at 3h, 24h and 48h decreased, and content of β-EP in blood plasma at 3h and 24h decreased when compared with group A(P<0.05). Conclusion Naloxone hydrochloride could decrease the c-fos expression in brain and β-EP level in blood plasma, alleviate the nerve injury, and protect neural function. The therapeutic effect of naloxone administered either after DBI and SBI or after DBI and before SBI was similar.
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Objective To study the change of expression of c-fos and c-jun when using IN-1 alone or combination with NT-3 after spinal cord injury. Methods 120 adult health Sprague-Dawley (SD) rats were random divided into three groups, including control group, IN-1 group, and IN-1 combination with NT-3 group. All rats were killed at the scheduled time and its myeloid tissues were taken out. In each group, the expression of c-fos and c-jun gene was detected by using reverse transcription- polymerase chain reaction technique ( RT-PCR ). Result The transcriptional levels of c-fos decreased and c-jun increased when using IN-1 alone, and the levels changed more when using IN-1 combination with NT-3. The peak of c-fos reached to 0. 974 ±0. 126 in control group, 0. 834 ±0. 047 in IN-1 group, and 0. 698 ±0. 052 in IN-1 combination with NT-3 group, and the peak of c-jun reached 0. 642 ±0. 048, 0. 712 ±0. 050, and 0. 814 ±0. 041, respectively. Conclusion One of the mechanisms of IN-1 and NT-3 to protect the spinal cord might be through inhibiting the expression of c-fos and enhancing the expression of c-jun.
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Objective To investigate the effect of penehyclidine hydrochloride (PHCD) on tramadol dependence and c-fos,△ FosB and M5 receptor expression in relevant brain regions in rats.Methods Thirty male adult SD rats weighing 180-220 g were randomly assigned to 3 groups (n =10 each):control group (group C),tramadol dependence group (group T) and PHCD group (group P).Tramadol dependence was induced by subcutaneous 10 mg/kg once a day for 7 consecutive days in groups T and P.PHCD 1.5 mg/kg was injected intraperitoneally on day 8 in group P,while in groups C and T the equal volume of normal saline was injected intraperitoneally instead of PHCD.The rats underwent conditioned place perference test at 30 min after intraperitoneal injection.The time spent in drug-paired side (gray area) was recorded.The rats were sacrificed after the conditioned place perference testand the brain was removed.The relevant brain regions (ventral tegmental area,prefrontal cortex,nucleus accumbens )were separated for determination of c-fos,△ FosB expression by Western blot and M5 receptor mRNA expression by RT-PCR.Results Compared with group C,the time spent in the drug-paired side (gray area) was significantly prolonged,and c-fos,△FosB and M5 receptor mRNA expressions were up-regulated in group T,△FosB and Ms receptor mRNA expressions were down-regulated in group P ( P ＜ 0.05 or 0.01 ).There was no significant difference in time spent in the drug-paired side (gray area) and c-fos expression between groups C and P( P ＞ 0.05).Compared with group T,the time spent in the drug-paired side (gray area) was significantly shortened,and c-fos,△ FosB and M5 receptor mRNA expressions were down-regulated in group P (P ＜0.01).Conclusion PHCD can significantly inhibit tramadol dependence by down-regulating c-fos,△FosB and M5 receptor expression in relevant brain regions.
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Objective To investigate the effect of tetramethylpyrazine pretreatment on the expression of cfos and heat shock protein (HSP70) during hypoxia-reoxygenation (H/R) in cultured fetal rat hippocampal neurons. Methods After the neurons were cultured and identified, they were randomly divided into 5 groups ( n = 24each): control group (group C), H/R group, and low, median and high concentration of tetramethylpyrazine pretreatment groups (group L, M and H). The neurons were exposed to 2 h of hypoxia followed by 24 h of reoxygenation. Tetramethylpyrazine was added with the final concentrations of 60, 200 and 800 μg/ml in group L, M and H respectively, and then the neurons were incubated for 1 h before H/R. The apoptosis rate, cell viability and expression of c-fos and HSP70 were detected. Results The cell viability was significantly lower, while the apoptosis rate was significantly higher in group A/R, L and H than in group C (P ＜0.01). The cell viability and HSP70expression were significantly higher, while the apoptosis rate and c-fos expression were significantly lower in group L, M and H than in group A/R, and in group M and H than in group L (P＜ 0.05). The cell viability and HSP70expression were significantly lower, while the apoptosis rate and c-fos expression were significantly higher in group H than in group M ( P ＜ 0.01 ).Conclusion The mechanism by which tetramethylpyrazine pretreatment inhibits the apoptosis in cultured fetal rat hippocampal neurons during H/R may be related to the dowm-regulation of c-fos expression and up-regulation of HSP70 expression.
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Objective To observe the expression of c-fos mRNA and protein in fluoride treated mouse fibroblast (FB) and osteoblast (OB) and to further explore the effects of c-fos in the osteogenic action of FB. Methods Mouse FB and OB were divided into control group and six fluoride groups (0, 0.0001, 0.0010, 0.1000, 1.0000, 10.0000,20.0000 mg/L F-), and the levels of c-fos protein at 2,4,24,48,72 h and c-fos mRNA at 48 h were measured by using ELISA and RT-PCR methods. Results Compared with the control group, fluoride increased the content of c-fos protein obviously in all FB group(P<0.01); and it is increased in 0.0001,0.0010 mg/L groups at 48 h (0.73±0.04, 0.64±0.14) and 0.0001 mg/L group at 72 h(0.70±0.17) in OB compared with the control group (0.32±0.04,0.27±0.05, P<0.01). Compared with the control group (0.95±0.11), RT-PCR revealed an increasing tendency of the expression of c-fos mRNA at 48 h in FB (1.06±0.16, 1.06±0.12,1.12±0.16,1.04±0.15,1.04±0.10,1.15±0.29), but the difference was not statistically significant(P>0.05); however, a statistically significant difference(P<0.01) of c-fos mRNA in 20.0000 mg/L group(1.40±0.17) in O B was found compared with the control group (1.06±0.06). Conclusion The higher expression of c-fos mRNA and protein in FB induced by fluoride may play an important role in the transformation of osteoblastic phenotype as well as increase the osteogenesis ability in FB.
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Objective To determine whether rizatriptan has an effect on cortical spreading depression (CSD) and c-Fos expression within periaqueductal grey (PAG) induced by CSD in rats. Methods The experimental SD rats were randomly divided into group A injected with KCl, group B KCl plus rizatriptan and group C NaCL The number and amplitude of CSD were recorded after KCl or NaCl injection. C-Fos positive neurons of different layer were identified by the immunohistochemical technique 2 hours after the first injection of KCl or NaCl. Results There was no CSD in group C. The number of CSD in group A ( 10.70±3.23 ) was significantly more than that in group B (6.10±2.56, t = - 3.528, P < 0.01 ). The amplitude of CSD in group A ( 17.33 (95% CI 11.45--23.11 ) mV) was significantly greater than that in group B (11.82 (95%CI 9.24--14.70) mV, Z= -4.360, P< 0.01). There were more cFos-like immnoreactive neurons in every layer in group A than in group C (P < 0.01 ) and in group B (P < 0.05 ). Conclusion Rizatriptan has an inhibitory effect on CSD, which might induce the headache through exciting the neurons in PAG.
ABSTRACT
Exposure to light can induce photoreceptor cell death and exacerbate retinal degeneration. In this study, mice with genetic knockout of several genes, including rhodopsin kinase (Rhok-/-), arrestin (Sag-/-), transducin (Gnat1-/-), c-Fos (c-Fos-/-) and arrestin/transducin (Sag-/-/Gnat1-/-), were examined. We measured the expression levels of thousands of genes in order to investigate their roles in phototransduction signaling in light-induced retinal degeneration using DNA microarray technology and then further explored the gene network using pathway analysis tools. Several cascades of gene components were induced or inhibited as a result of corresponding gene knockout under specific light conditions. Transducin deletion blocked the apoptotic signaling induced by exposure to low light conditions, and it did not require c-Fos/AP-1. Deletion of c-Fos blocked the apoptotic signaling induced by exposure to high intensity light. In the present study, we identified many gene transcripts that are essential for the initiation of light-induced rod degeneration and proposed several important networks that are involved in pro- and anti-apoptotic signaling. We also demonstrated the different cascades of gene components that participate in apoptotic signaling under specific light conditions.