BACKGROUND： Hypoxia and ischemia induce neuronal damage, decreased neuronal numbers and synaptophysin levels, and deficits in learning and memory functions. Previous studies have shown that lycium barbarum polysaccha...BACKGROUND： Hypoxia and ischemia induce neuronal damage, decreased neuronal numbers and synaptophysin levels, and deficits in learning and memory functions. Previous studies have shown that lycium barbarum polysaccharide, the most effective component of barbary wolfberry fruit, has protective effects on neural cells in hypoxia-ischemia. OBJECTIVE： To investigate the effects of Naotan Pill on glutamate-treated neural cells and on cognitive function in juvenile rats following hypoxia-ischemia. DESIGN, TIME AND SETTING： The randomized, controlled, in vivo study was performed at the Cell Laboratory of Lanzhou University, Lanzhou Institute of Modern Physics of Chinese Academy of Sciences, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from December 2005 to August 2006. The cellular neurobiology, in vitro experiment was conducted at the Institute of Human Anatomy, Histology, Embryology and Neuroscience, School of Basic Medical Sciences, Lanzhou University, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from March 2007 to January 2008. MATERIALS： Naotan Pill, composed of barbary wolfberry fruit, danshen root, grassleaf sweetflag rhizome, and glossy privet fruit, was prepared by Gansu Provincial Rehabilitation Center, China. Rabbit anti-synaptophysin, choline acetyl transferase polyclonal antibody, streptavidin-biotin complex kit and diaminobenzidine kit （Boster, Wuhan, China）, as well as glutamate （Hualian, Shanghai, China） were used in this study. METHODS： Cortical neural cells were isolated from neonatal Wistar rats. Neural cell damage models were induced using glutamate, and administered Naotan Pill prior to and following damage. A total of 54 juvenile Wistar rats were equally and randomly assigned into model, Naotan Pill, and sham operation groups. The left common carotid artery was ligated, and then rat models of hypoxic-ischemic injury were assigned to the model and Naotan Pill groups. At 2 days following model induction, rats in the Naotan Pill group were administered Naotan Pillsuspension for 21 days. In the model and sham operation groups, rats received an equal volume of saline. MAIN OUTCOME MEASURES： Neural cell morphology was observed using an inverted phase contrast microscope. Survival rate of neural cells was measured by MTT assay. Synaptophysin and choline acetyl transferase expression was observed in the hippocampal CA1 region of juvenile rats using immunohistochemistry. Cognitive function was tested by the Morris water maze. RESULTS： Pathological changes were detected in glutamate-treated neural cells. Neural cell morphology remained normal after Naotan Pill intervention. Absorbance and survival rate of neural cells were significantly greater following Naotan Pill intervention, compared to glutamate-treated neural cells （P 〈 0.05）. Synaptophysin and choline acetyl transferase expression was lowest in the hippocampal CA1 region in the model group and highest in the sham operation group. Significant differences among groups were observed （P 〈 0.05）. Escape latency and swimming distance were significantly longer in the model group compared to the Naotan Pill group （P 〈 0.05）. CONCLUSION： Naotan Pill exhibited protective and repair effects on glutamate-treated neural cells. Naotan Pill upregulated synaptophysin and choline acetyl transferase expression in the hippocampus and improved cognitive function in rats following hypoxia-ischemia.展开更多
Play development in juvenile rats depends on specific sensory signals integrated at cortical, limbic and brain stem levels to modulate motoric, metabolic, motivational and social responses. Neonatal undernourishment d...Play development in juvenile rats depends on specific sensory signals integrated at cortical, limbic and brain stem levels to modulate motoric, metabolic, motivational and social responses. Neonatal undernourishment disrupts the morphological and functional organization of the brain for adaptive responses including play performance. These alterations may be restored by preweaning exposure to sensory-enriched environments. This study was designed to determine in four experimental groups, Control (LC), Underfed (LU), Control Ligated/Stimulated (LCS), and Underfed Ligated/Stimulated (LUS), whether changes in juvenile play of neonatally underfed male rats by the nipple-ligated procedure of F0 dams and/or the handling of F1 rats may restore the deficiencies in juvenile play performance. The pinning frequency values in LC, LCS and LUS groups consistently increased until reaching a significant peak between postnatal days (PDs) 25 and 50 and then gradually declining until PD 60, when the play in pairs was significantly higher compared with the play in groups that follows the same sequence but with lower values in the stimulated groups. The results may reflect poor maternal care and lower somatosensory stimulation;and the sensory massage of LU F1 pups compared with the LC, LUS, and LCS rats. Fewer dorsal body contacts occurred in LU and LUS rats when playing in pairs than in groups. Results suggest that although handling has salutary effects on neuronal play structures, the reduced levels of total pinning and dorsal contacts, mainly in the play of rat pairs in LCS vs. LUS groups, were not fully recovered.展开更多
As the major division of the basal ganglia, neostriatum forms mutual connections with multiple brain areas and is critically involved in motor control and learning/memory. Long-term synaptic plasticity has been widely...As the major division of the basal ganglia, neostriatum forms mutual connections with multiple brain areas and is critically involved in motor control and learning/memory. Long-term synaptic plasticity has been widely studied in different species recently. However, there are rare reports about the short-term synaptic plasticity in neostratium. In the present study, using field excitatory postsynaptic potentials recording, we reported one form of short-term synaptic plasticity that is paired pulse depression in juvenile rat dorsal striatum slices induced by stimuli of the white matter. The field excitatory postsynaptic potentials could be abolished by α-amino-3-hydroxy-5-methylizoxazole-4-propionic acid receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, but not by gamma-aminobutyric acid type A receptor antagonist bicuculline or dopamine D1 receptor antagonist SKF-81297. The paired pulse depression in the corticostratial pathway was different from paired pulse facilitation in the hippocampal CA1 synapse. In addition, the paired pulse depression was not affected by bath application of gamma-aminobutyric acid type A receptor antagonist or dopamine D1 receptor antagonist. However, low calcium and high magnesium could attenuate the paired pulse depression. These findings suggest a more complicated plasticity form in the dorsal striatum of juvenile rats that is different from that in the hippocampus, which is related with extracellular calcium.展开更多
The effect of Batroxobin on expression of c-Jun in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemistry methods. The results showed that...The effect of Batroxobin on expression of c-Jun in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats, and at the same time c-Jun expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of c-Jun immune reactive cells of Batroxobin-treated rats was also less than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder in temporal ischemic rats, and the down-regulation of the expression of c-Jun is probably related to the neuroprotective mechanism.展开更多
BACKGROUND Various animal models have been used to explore the pathogenesis of choledochal cysts(CCs),but with little convincing results.Current surgical techniques can achieve satisfactory outcomes for treatment of C...BACKGROUND Various animal models have been used to explore the pathogenesis of choledochal cysts(CCs),but with little convincing results.Current surgical techniques can achieve satisfactory outcomes for treatment of CCs.Consequently,recent studies have focused more on clinical issues rather than basic research.Therefore,we need appropriate animal models to further basic research.AIM To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs.METHODS Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group,sham surgical group,or control group.A rat model of CC was established by partial ligation of the bile duct.The reliability of the model was confirmed by measurements of serum biochemical indices,morpho-logy of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues.RESULTS Dilation classified as mild(diameter,≥1 mm to<3 mm),moderate(≥3 mm to<10 mm),and severe(≥10 mm)was observed in 17,17,and 2 rats in the surgical group,respectively,while no dilation was observed in the control and sham surgical groups.Serum levels of alanine aminotransferase,aspartate aminotrans-ferase,total bilirubin,direct bilirubin,and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery,while direct bilirubin,total bilirubin,and gamma-glutamyltransferase were further increased 14 d after surgery.Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery.The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues.CONCLUSION The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC,which may contribute to investigating the pathogenesis of CC.展开更多
Objective:To explore the effect of age on Qingkailing Granules disposition by comparing the pharmacoknetics of geniposide and baicalin in juvenile and adult rats.Methods:A simple and rapid LC-MS/MS method was develope...Objective:To explore the effect of age on Qingkailing Granules disposition by comparing the pharmacoknetics of geniposide and baicalin in juvenile and adult rats.Methods:A simple and rapid LC-MS/MS method was developed and validated to simultaneously determine geniposide and baicalin in rat plasma after a simple protein precipitation.The analytes were separated on an Agilent ZORBAX Extend-C18 column.The mobile phase consisted of acetonitrile and water with 0.1%(volume percent)formic acid at a flow rate of 0.6 mL/min.The ionization was conducted using an ESI source in negative ion mode.Multiple reaction monitoring was used for quantification at transitions of m/z 445.0→m/z 268.9 for baicalin,m/z 433.2→m/z 225.0 for geniposide,m/z 431.0→m/z341.0 for vitexin(IS).Juvenile and adult rats were administrated Qingkailing Granules(3 g/kg)orally.Plasma concentrations of baicalin and geniposide were determined by LC-MS/MS.Results:The linear ranges of the analytes were 1-1000 ng/mL for baicalin and 2-2000 ng/mL for geniposide.The method was successfully applied to compare the pharmacokinetics of the analytes between juvenile and adult rats after oral administration of Qingkailing Granules.AUC was bigger in adult rats,while t1/2 was longer in juvenile rats.Conclusion:These results suggested that the absorption and elimination of baicalin and geniposide in juvenile rats was lower than that in adult rats.Additional attention should be paid to the pharmacokinetic difference when Qingkailing Granules were used in children.展开更多
Objective To investigate the effect of graded hypothermia on neuropathologic alterations of neonatal rat brain after exposed to hypoxic-ischemic insult at 37℃, 33℃, 31℃, and 28℃, respectively, and to observe the e...Objective To investigate the effect of graded hypothermia on neuropathologic alterations of neonatal rat brain after exposed to hypoxic-ischemic insult at 37℃, 33℃, 31℃, and 28℃, respectively, and to observe the effect of hypothermia on 72-kDa heat shock protein （HSP72） expression after hypoxic-ischemic insult. Methods Seven days old Wistar rats were subjected to unilateral common carotid artery ligation followed by exposure to hypoxia in 8% oxygen for 2 hours at 37℃, 33℃, 31℃, and 28℃, respectively. The brain temperature was monitored indirectly by inserting a mini-thermocouple probe into the temporal muscle during hypoxia. After hypoxia-ischemia their mortality was assessed. Neuronal damage was assessed with HE staining 72 hours after hypoxia. HSP72 expression at 0.5, 24, and 72 hours of recovery was immunohistochemically assessed using a monoclonal antibody to HSP72. Results Hypoxia-ischemia caused 10.5% （2 / 19） of mortality in rat of 37℃ group, but no death oc- curred in 33℃, 31℃ or 28℃ groups. HE staining showed neuropathologic damage was extensive in rats exposed to hypoxia-ischemia at 37℃ （more than 80.0%）. The incidence of severe brain damage was significantly decreased in 33℃ （53.3%） and 31℃ groups （44,4%）, and no histologic injury was seen in the 28℃ group of rats. Expression of HSP72 was manifest and persistent in the rat brain of 37℃ group, but minimum in the rat brain of 28℃ group. Conclusion Mild and moderate hypothermia might prevent cerebral visible neuropathologic damage associated with hypoxic-ischemic injury by decreasing stress response.展开更多
BACKGROUND： Pharmacological experiments have demonstrated that gastrodin has a protective effect on neonatal rat brain subjected to hypoxia-ischemia; however, the underlying mechanism has not been fully elucidated. O...BACKGROUND： Pharmacological experiments have demonstrated that gastrodin has a protective effect on neonatal rat brain subjected to hypoxia-ischemia; however, the underlying mechanism has not been fully elucidated. OBJECTIVE： The aim of this study was to investigate the acute therapeutic effects of gastrodin by observing prostaglandin B2 and 6-keto-prostaglandin F 1 a in brain tissue of neonatal rats that received gastrodin injections immediately after hypoxia-ischemia. DESIGN： Single-factor design. SETTING： Department of Pediatrics, Affiliated Hospital of Yanbian University. MATERIALS： This study was performed in the Laboratory of the Department of Pediatrics, Affiliated Hospital of Yanbian University （key laboratory of provincial Health Department） from April to December 2003. Fifty-five Wistar rats of either gender, aged 7 days, were provided by the Laboratory Animal Center of Affiliated Hospital of Yanbian University. The rats were randomly divided into normal control （n =10）, model （n = 15）, gastrodin-treated （n = 15）, and Danshen-treated （n = 15） groups. The protocol was performed in accordance with guidelines from the Institute of Health Sciences for the use and care of animals. The following reagents were. used： Gastrodin （Sancai Medicine Group Co., Ltd., Zhongshan, Guangdong Province, China; component： gastrodin）, Danshen （Conba Stock Company, Jinhua, Zhengjiang Province, China; component： salvia miltiorrhiza）, and reagent kits for ^125I-prostaglandin B2 and ^125I-6-prostaglandin F l a （Research and Development Center for Science and Technology, General Hospital of Chinese PLA）. METHODS： Rats in the normal control group received no treatment. Rats in the remaining 3 groups were anesthetized, followed by ligation of the left common carotid artery. One hour later, the rats were placed in a closed hypoxic box and allowed to inhale 8% oxygen-air （2.0 3.0 L/min） for 2 hours to develop hypoxic-ischemic encephalopathy. Immediately after lesion, rats in the gastrodin and Danshen-treated groups were intraperitoneally injected with l g gastrodin （10 mL/kg） and 15 g Danshen （l 5 mL/kg）, respectively. MAIN OUTCOME MEASURES： Forty-eight hours after lesion, the left brain hemisphere was removed and homogenized to test the levels of prostaglandin B2 and 6-keto-prostaglandin F 1 a by radioimmunoassay. RESULTS： Forty successfully lesioned neonatal rats from the model, gastrodin-treated, and Danshen-treated groups, and ten rats from the control group, were included in the final analysis. Levels of prostaglandin B2 and 6-keto-prostaglandin F 1 a in brain tissue of neonatal rats were significantly higher in the model group than in the control group （both P 〈 0.01）. Levels of prostaglandin B2 and 6-keto-prostaglandin F 1 a were significantly lower in the gastrodin-treated and the Danshen-treated groups compared to the model group （all P 〈 0.01）. However, there were no significant differences in levels of prostaglandin B2 and 6-keto-prostaglandin F 1 a between the gastrodin-treated and the Danshen-treated groups （P 〉 0.05）. CONCLUSION： Gastrodin decreased prostaglandin and thromboxan levels in neonatal rat brains subjected to hypoxia-ischemia.展开更多
基金the Nomarch Foundation Program of Gansu Province,No. Gs024-A43-015the Foundation of General Charity Committee of Gansu Province
文摘BACKGROUND： Hypoxia and ischemia induce neuronal damage, decreased neuronal numbers and synaptophysin levels, and deficits in learning and memory functions. Previous studies have shown that lycium barbarum polysaccharide, the most effective component of barbary wolfberry fruit, has protective effects on neural cells in hypoxia-ischemia. OBJECTIVE： To investigate the effects of Naotan Pill on glutamate-treated neural cells and on cognitive function in juvenile rats following hypoxia-ischemia. DESIGN, TIME AND SETTING： The randomized, controlled, in vivo study was performed at the Cell Laboratory of Lanzhou University, Lanzhou Institute of Modern Physics of Chinese Academy of Sciences, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from December 2005 to August 2006. The cellular neurobiology, in vitro experiment was conducted at the Institute of Human Anatomy, Histology, Embryology and Neuroscience, School of Basic Medical Sciences, Lanzhou University, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from March 2007 to January 2008. MATERIALS： Naotan Pill, composed of barbary wolfberry fruit, danshen root, grassleaf sweetflag rhizome, and glossy privet fruit, was prepared by Gansu Provincial Rehabilitation Center, China. Rabbit anti-synaptophysin, choline acetyl transferase polyclonal antibody, streptavidin-biotin complex kit and diaminobenzidine kit （Boster, Wuhan, China）, as well as glutamate （Hualian, Shanghai, China） were used in this study. METHODS： Cortical neural cells were isolated from neonatal Wistar rats. Neural cell damage models were induced using glutamate, and administered Naotan Pill prior to and following damage. A total of 54 juvenile Wistar rats were equally and randomly assigned into model, Naotan Pill, and sham operation groups. The left common carotid artery was ligated, and then rat models of hypoxic-ischemic injury were assigned to the model and Naotan Pill groups. At 2 days following model induction, rats in the Naotan Pill group were administered Naotan Pillsuspension for 21 days. In the model and sham operation groups, rats received an equal volume of saline. MAIN OUTCOME MEASURES： Neural cell morphology was observed using an inverted phase contrast microscope. Survival rate of neural cells was measured by MTT assay. Synaptophysin and choline acetyl transferase expression was observed in the hippocampal CA1 region of juvenile rats using immunohistochemistry. Cognitive function was tested by the Morris water maze. RESULTS： Pathological changes were detected in glutamate-treated neural cells. Neural cell morphology remained normal after Naotan Pill intervention. Absorbance and survival rate of neural cells were significantly greater following Naotan Pill intervention, compared to glutamate-treated neural cells （P 〈 0.05）. Synaptophysin and choline acetyl transferase expression was lowest in the hippocampal CA1 region in the model group and highest in the sham operation group. Significant differences among groups were observed （P 〈 0.05）. Escape latency and swimming distance were significantly longer in the model group compared to the Naotan Pill group （P 〈 0.05）. CONCLUSION： Naotan Pill exhibited protective and repair effects on glutamate-treated neural cells. Naotan Pill upregulated synaptophysin and choline acetyl transferase expression in the hippocampus and improved cognitive function in rats following hypoxia-ischemia.
文摘Play development in juvenile rats depends on specific sensory signals integrated at cortical, limbic and brain stem levels to modulate motoric, metabolic, motivational and social responses. Neonatal undernourishment disrupts the morphological and functional organization of the brain for adaptive responses including play performance. These alterations may be restored by preweaning exposure to sensory-enriched environments. This study was designed to determine in four experimental groups, Control (LC), Underfed (LU), Control Ligated/Stimulated (LCS), and Underfed Ligated/Stimulated (LUS), whether changes in juvenile play of neonatally underfed male rats by the nipple-ligated procedure of F0 dams and/or the handling of F1 rats may restore the deficiencies in juvenile play performance. The pinning frequency values in LC, LCS and LUS groups consistently increased until reaching a significant peak between postnatal days (PDs) 25 and 50 and then gradually declining until PD 60, when the play in pairs was significantly higher compared with the play in groups that follows the same sequence but with lower values in the stimulated groups. The results may reflect poor maternal care and lower somatosensory stimulation;and the sensory massage of LU F1 pups compared with the LC, LUS, and LCS rats. Fewer dorsal body contacts occurred in LU and LUS rats when playing in pairs than in groups. Results suggest that although handling has salutary effects on neuronal play structures, the reduced levels of total pinning and dorsal contacts, mainly in the play of rat pairs in LCS vs. LUS groups, were not fully recovered.
基金supported by a grant from the Canadian Institutes of Health Research, No. 15514 & 44008
文摘As the major division of the basal ganglia, neostriatum forms mutual connections with multiple brain areas and is critically involved in motor control and learning/memory. Long-term synaptic plasticity has been widely studied in different species recently. However, there are rare reports about the short-term synaptic plasticity in neostratium. In the present study, using field excitatory postsynaptic potentials recording, we reported one form of short-term synaptic plasticity that is paired pulse depression in juvenile rat dorsal striatum slices induced by stimuli of the white matter. The field excitatory postsynaptic potentials could be abolished by α-amino-3-hydroxy-5-methylizoxazole-4-propionic acid receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, but not by gamma-aminobutyric acid type A receptor antagonist bicuculline or dopamine D1 receptor antagonist SKF-81297. The paired pulse depression in the corticostratial pathway was different from paired pulse facilitation in the hippocampal CA1 synapse. In addition, the paired pulse depression was not affected by bath application of gamma-aminobutyric acid type A receptor antagonist or dopamine D1 receptor antagonist. However, low calcium and high magnesium could attenuate the paired pulse depression. These findings suggest a more complicated plasticity form in the dorsal striatum of juvenile rats that is different from that in the hippocampus, which is related with extracellular calcium.
文摘The effect of Batroxobin on expression of c-Jun in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats, and at the same time c-Jun expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of c-Jun immune reactive cells of Batroxobin-treated rats was also less than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder in temporal ischemic rats, and the down-regulation of the expression of c-Jun is probably related to the neuroprotective mechanism.
基金the Key R&D Program of Zhejiang,No.2023C03029Health Science and Technology Plan of Zhejiang Province,No.2022RC201Zhejiang Provincial Natural Science Foundation Project,No.LY20H030007.
文摘BACKGROUND Various animal models have been used to explore the pathogenesis of choledochal cysts(CCs),but with little convincing results.Current surgical techniques can achieve satisfactory outcomes for treatment of CCs.Consequently,recent studies have focused more on clinical issues rather than basic research.Therefore,we need appropriate animal models to further basic research.AIM To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs.METHODS Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group,sham surgical group,or control group.A rat model of CC was established by partial ligation of the bile duct.The reliability of the model was confirmed by measurements of serum biochemical indices,morpho-logy of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues.RESULTS Dilation classified as mild(diameter,≥1 mm to<3 mm),moderate(≥3 mm to<10 mm),and severe(≥10 mm)was observed in 17,17,and 2 rats in the surgical group,respectively,while no dilation was observed in the control and sham surgical groups.Serum levels of alanine aminotransferase,aspartate aminotrans-ferase,total bilirubin,direct bilirubin,and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery,while direct bilirubin,total bilirubin,and gamma-glutamyltransferase were further increased 14 d after surgery.Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery.The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues.CONCLUSION The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC,which may contribute to investigating the pathogenesis of CC.
基金National Natural Science Foundation of China(No.81903706)Shandong Provincial Natural Science Foundation(ZR2019BH069)for financial support。
文摘Objective:To explore the effect of age on Qingkailing Granules disposition by comparing the pharmacoknetics of geniposide and baicalin in juvenile and adult rats.Methods:A simple and rapid LC-MS/MS method was developed and validated to simultaneously determine geniposide and baicalin in rat plasma after a simple protein precipitation.The analytes were separated on an Agilent ZORBAX Extend-C18 column.The mobile phase consisted of acetonitrile and water with 0.1%(volume percent)formic acid at a flow rate of 0.6 mL/min.The ionization was conducted using an ESI source in negative ion mode.Multiple reaction monitoring was used for quantification at transitions of m/z 445.0→m/z 268.9 for baicalin,m/z 433.2→m/z 225.0 for geniposide,m/z 431.0→m/z341.0 for vitexin(IS).Juvenile and adult rats were administrated Qingkailing Granules(3 g/kg)orally.Plasma concentrations of baicalin and geniposide were determined by LC-MS/MS.Results:The linear ranges of the analytes were 1-1000 ng/mL for baicalin and 2-2000 ng/mL for geniposide.The method was successfully applied to compare the pharmacokinetics of the analytes between juvenile and adult rats after oral administration of Qingkailing Granules.AUC was bigger in adult rats,while t1/2 was longer in juvenile rats.Conclusion:These results suggested that the absorption and elimination of baicalin and geniposide in juvenile rats was lower than that in adult rats.Additional attention should be paid to the pharmacokinetic difference when Qingkailing Granules were used in children.
文摘Objective To investigate the effect of graded hypothermia on neuropathologic alterations of neonatal rat brain after exposed to hypoxic-ischemic insult at 37℃, 33℃, 31℃, and 28℃, respectively, and to observe the effect of hypothermia on 72-kDa heat shock protein （HSP72） expression after hypoxic-ischemic insult. Methods Seven days old Wistar rats were subjected to unilateral common carotid artery ligation followed by exposure to hypoxia in 8% oxygen for 2 hours at 37℃, 33℃, 31℃, and 28℃, respectively. The brain temperature was monitored indirectly by inserting a mini-thermocouple probe into the temporal muscle during hypoxia. After hypoxia-ischemia their mortality was assessed. Neuronal damage was assessed with HE staining 72 hours after hypoxia. HSP72 expression at 0.5, 24, and 72 hours of recovery was immunohistochemically assessed using a monoclonal antibody to HSP72. Results Hypoxia-ischemia caused 10.5% （2 / 19） of mortality in rat of 37℃ group, but no death oc- curred in 33℃, 31℃ or 28℃ groups. HE staining showed neuropathologic damage was extensive in rats exposed to hypoxia-ischemia at 37℃ （more than 80.0%）. The incidence of severe brain damage was significantly decreased in 33℃ （53.3%） and 31℃ groups （44,4%）, and no histologic injury was seen in the 28℃ group of rats. Expression of HSP72 was manifest and persistent in the rat brain of 37℃ group, but minimum in the rat brain of 28℃ group. Conclusion Mild and moderate hypothermia might prevent cerebral visible neuropathologic damage associated with hypoxic-ischemic injury by decreasing stress response.
文摘BACKGROUND： Pharmacological experiments have demonstrated that gastrodin has a protective effect on neonatal rat brain subjected to hypoxia-ischemia; however, the underlying mechanism has not been fully elucidated. OBJECTIVE： The aim of this study was to investigate the acute therapeutic effects of gastrodin by observing prostaglandin B2 and 6-keto-prostaglandin F 1 a in brain tissue of neonatal rats that received gastrodin injections immediately after hypoxia-ischemia. DESIGN： Single-factor design. SETTING： Department of Pediatrics, Affiliated Hospital of Yanbian University. MATERIALS： This study was performed in the Laboratory of the Department of Pediatrics, Affiliated Hospital of Yanbian University （key laboratory of provincial Health Department） from April to December 2003. Fifty-five Wistar rats of either gender, aged 7 days, were provided by the Laboratory Animal Center of Affiliated Hospital of Yanbian University. The rats were randomly divided into normal control （n =10）, model （n = 15）, gastrodin-treated （n = 15）, and Danshen-treated （n = 15） groups. The protocol was performed in accordance with guidelines from the Institute of Health Sciences for the use and care of animals. The following reagents were. used： Gastrodin （Sancai Medicine Group Co., Ltd., Zhongshan, Guangdong Province, China; component： gastrodin）, Danshen （Conba Stock Company, Jinhua, Zhengjiang Province, China; component： salvia miltiorrhiza）, and reagent kits for ^125I-prostaglandin B2 and ^125I-6-prostaglandin F l a （Research and Development Center for Science and Technology, General Hospital of Chinese PLA）. METHODS： Rats in the normal control group received no treatment. Rats in the remaining 3 groups were anesthetized, followed by ligation of the left common carotid artery. One hour later, the rats were placed in a closed hypoxic box and allowed to inhale 8% oxygen-air （2.0 3.0 L/min） for 2 hours to develop hypoxic-ischemic encephalopathy. Immediately after lesion, rats in the gastrodin and Danshen-treated groups were intraperitoneally injected with l g gastrodin （10 mL/kg） and 15 g Danshen （l 5 mL/kg）, respectively. MAIN OUTCOME MEASURES： Forty-eight hours after lesion, the left brain hemisphere was removed and homogenized to test the levels of prostaglandin B2 and 6-keto-prostaglandin F 1 a by radioimmunoassay. RESULTS： Forty successfully lesioned neonatal rats from the model, gastrodin-treated, and Danshen-treated groups, and ten rats from the control group, were included in the final analysis. Levels of prostaglandin B2 and 6-keto-prostaglandin F 1 a in brain tissue of neonatal rats were significantly higher in the model group than in the control group （both P 〈 0.01）. Levels of prostaglandin B2 and 6-keto-prostaglandin F 1 a were significantly lower in the gastrodin-treated and the Danshen-treated groups compared to the model group （all P 〈 0.01）. However, there were no significant differences in levels of prostaglandin B2 and 6-keto-prostaglandin F 1 a between the gastrodin-treated and the Danshen-treated groups （P 〉 0.05）. CONCLUSION： Gastrodin decreased prostaglandin and thromboxan levels in neonatal rat brains subjected to hypoxia-ischemia.
