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OBJECTIVE To expl ore the mechanism of effe ctive fractions from Xiongma decoction in the treatment of migraine with hyperactivity of liver-yang and blood stasis. METHODS Totally 70 male SD rats were randomly divided into normal group ， model group ，positive control group （Flunarizine hydrochloride capsules 0.9 mg/kg），low-dose and high-dose groups of Xiongma decoction effective fractions （ethyl acetate extract 0.87，3.46 g/kg，n-butanol extract 1.80，7.20 g/kg）. Except for normal group ， rats in other groups were given aconite decoction （2 g/kg），once a day ，for 4 consecutive weeks to establish the hyperactivity model of liver-yang. On the 15th day of modeling ，all administration groups were given corresponding drugs intragastrically at the same time ，once a day ，for 2 consecutive weeks. On the 29th day of modeling ，rats trigeminal ganglion was stimulated to establish the migraine model with hyperactivity of liver-yang and blood stasis ，then the medication was maintained for another time according to the above method. The macroscopic signs and behavior of the rats were observed ；positive expression ，mRNA and protein expression of transient receptor potential vanilloid 1 （TRPV1），calcitonin generelated peptide （CGRP），calcitonin receptor-like receptor （CRLR） and receptor-associated membrane proteins 1 （RAMP1） in trigeminal cervical spinal complex （TCC） were detected by immunohistochemistry ，RT-qPCR and Western blot assay. RESULTS Rats in model group showed macrophysical signs and behaviora l manifestations related to migraine with hyperactivity of liver-yang and blood stasis. Thirty minutes after last administration ，the above conditions of rats in Xiongma decoction effective fraction groups were improved significantly. Compared with normal group ， positive expression，mRNA and protein expression of TRPV 1，CGRP， CRLR and RAMP 1 in TCC of rats in the model group were significantly increased （P＜0.05）. Compared with model zengguirong@hnse.org group， most of above indicators in Xiongma decoction effective fraction groups were significantly decreased （P＜0.05）. CONCLUSIONS The mechanism of Xiongma decoction in preventing and treating migraine with hyperactivity of liver-yang and blood stasis may be related to inhibit the activity of TRPV1-CGRP/CGRP receptor signaling pathway in TCC.
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ABSTRACT OBJECTIVE：To study the effects of the extract of Xiongmatang on 5-HT and CGRP in brain tissue of rats with liver-yang hyperactivity and blood stagnation migraine. METHODS：Fifty male spontaneously hypertension （SHR） rats were randomly divided into model control group，Zhengtian pill positive control group （1.6 g/kg），the extract of Xiongmatang low-dose，medium-dose and high-dose groups（4.5，9.0，18.0 g/kg，by crude drug），with 10 rats in each group. Another 10 normal rats were taken as normal control group. Administration group was given relevant medicine intragastrically，once a day，for consecutive 28 d. Normal control group and model control group were given equal volume normal saline intragastrically. After last administration，except for normal control group，other groups were used to stimulate trigeminal ganglia（10 min）to establish liver-yang hyperactivity and blood stagnation migraine model，and maintained the administration once more after making the model. 30 min later，general behavior and tongue quality of rats were observed，and the blood pressure was measured；the contents of 5-HT and CGRP in cerebral tissue of rats were determined by ELISA. The protein expression of CGRP in cerebral tissue of rats were determined by Western blot method. RESULTS： Compared with the normal control group， the rats in the model control group had behavioral symptoms，such as the color of conjunctiva deepened and reddened， excessive hairdressing，head flicking，and most of the rats had purple tongue；the systolic pressure and the content and protein expression of CGRP were all increased obviously（P＜0.05 or P＜0.01）， while the content of 5-HT in cerebral tissue was decreased obviously（P＜0.01）. Compared with model control group，general behavior and tongue quality of rats were improved significantly in administration groups. Systolic pressure，the content and the protein expression of CGRP in cerebral tissue of rats were decreased significantly in Zhengtian pill positive control group and the extract of Xiongmatang high-dose group （P＜0.05），while the content of 5-HT in cerebral tissue of rats were increased significantly in Zhengtian pill positive control group，the extract of Xiongmatang medium-dose and high-dose groups（P＜0.05）.CONCLUSIONS：The extract of Xiongmatang has obvious protective effect on liver-yang hyperactivity and blood stagnation migraine model rats，the mechanism of which may be associated with reducing the content of CGRP in cerebral tissue and raising the content of 5-HT in cerebral tissue
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Adipocytokines are polypeptides or proteins that are secreted by fat cells with a wide range of biological activities. Adiponectin is a fatty cytokine with insulin sensitization. It possesses the function of anti- diabetes, atherosclerosis and anti-inflammation. Adiponectin may participate in regulating the development of cognitive impairment, which is considered as a new regulatory factor for cognitive impairment.
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Humans , Adiponectin , Cognitive Dysfunction , Diabetes Mellitus , Insulin , Insulin ResistanceABSTRACT
Objective@#To observe the improving effect of Hypericum Perforatum L Extracts (HPLES)on depression induced by chronic unpredictable mild stress in mice.@*Methods@#The depression model was established by the method of chronic unpredictable mild stress. Fifty depression model mice were divided into model control group, fluoxetine hydrochloride group (2.6 mg / kg), Hypericum perforatum extract low, medium and high (0.2 g / kg, 0.4 g / kg, 0.8 g / kg) dose groups according to the random number table method. Another 10 normal mice matched with body weight were taken as the normal control group. The mice in normal control group and the model control group were given pure water by gavage every day, and the mice in other groups were given corresponding solution by gavage for 4 weeks. In addition to the normal control group, the mice in other groups continued to undergo chronic unpredictable mild stress during gavage.The sugar water preference test and forced swimming test were performed after the last administration. Blood samples were collected from the posterior orbital venous plexus, and the levels of dopamine (DA) and brain-derived neurotrophic factor (BDNF) were measured by Elisa. The hippocampal tissues of mice were examined by HE staining.@*Results@#Compared with the normal control group, the body mass of mice in the model control group decreased significantly at the first, second, third and fourth weeks (t=2.739, 4.162, 4.082, 3.957; all P<0.05). At the first, second, third and fourth weeks, the body mass of mice in the low, middle and high dose group of Hypericum perforatum extract were not significantly different from those in the model control group (all P>0.05). Compared with the normal control group, the sugar water preference index of mice in the model control group was significantly reduced((61.3±4.5)%, (52.6±5.2)%; t=2.721, P<0.05), the swimming immobility time was prolonged((44.3±20.00) s, (101.8±50.8) s; t=2.939, P<0.05), the difference were statistically significant. Compared with the model control group, the sugar water preference index of mice in the low, middle and high dose group of Hypericum perforatum extract increased((61.8±4.7)%, (65.2±4.1)%, (62.6±5.6)%, t=-3.005, 5.073, -2.928, all P<0.05), the swimming immobility time decreased ((47.2±17.9) s, (54.8±50.3) s, (61.3±44.2) s; t=2.803, 1.921, 1.903, all P<0.05). The results of Elisa showed that compared with the normal control group, the levels of serum DA and BDNF of mice in the model control group were significantly lower (t=3.031, 8.507, all P<0.05); compared with the model control group, the levels of serum DA of mice in the low dose and high dose group of Hypericum perforatum were significantly higher (t=5.025, 3.414, P<0.05), and the serum BDNF of mice in the high dose group of Hypericum perforatum was also significantly higher (t=6.098, P<0.05), the difference was statistically significant. HE staining showed that compared with the normal control group, the neurons in CA3 area of hippocampus in the model control group mice were seriously damaged, suggesting the establishment of the mouse model. Compared with the model control group, the atrophy and degeneration of hippocampal CA3 cells in the three dose groups were significantly reduced. The atrophy and deformation of hippocampal CA3 neurons in the low, middle and high dose groups of Hypericum perforatum extract were relieved.@*Conclusion@#HPLES have obvious improving and antidepressant effects on the depression model mice induced by chronic unpredictable stress.The above effects may be related to the improvement of serum DA, DBNF level and reduce neuronal damage in CA3 area.
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Objective To observe the improving effect of Hypericum Perforatum L Extracts (HPLES)on depression induced by chronic unpredictable mild stress in mice. Methods The depression model was established by the method of chronic unpredictable mild stress. Fifty depression model mice were divided into model control group,fluoxetine hydrochloride group (2. 6 mg / kg),Hypericum perforatum ex-tract low,medium and high (0. 2 g / kg,0. 4 g / kg,0. 8 g / kg) dose groups according to the random num-ber table method. Another 10 normal mice matched with body weight were taken as the normal control group. The mice in normal control group and the model control group were given pure water by gavage every day,and the mice in other groups were given corresponding solution by gavage for 4 weeks. In addition to the normal control group,the mice in other groups continued to undergo chronic unpredictable mild stress during gavage. The sugar water preference test and forced swimming test were performed after the last administration. Blood samples were collected from the posterior orbital venous plexus,and the levels of dopamine (DA) and brain-derived neurotrophic factor (BDNF) were measured by Elisa. The hippocampal tissues of mice were exam-ined by HE staining. Results Compared with the normal control group,the body mass of mice in the model control group decreased significantly at the first,second,third and fourth weeks ( t=2. 739,4. 162,4. 082, 3. 957;all P<0. 05). At the first,second,third and fourth weeks,the body mass of mice in the low,middle and high dose group of Hypericum perforatum extract were not significantly different from those in the model control group (all P>0. 05). Compared with the normal control group,the sugar water preference index of mice in the model control group was significantly reduced((61. 3± 4. 5)%,(52. 6± 5. 2)%; t=2. 721,P<0. 05),the swimming immobility time was prolonged(( 44. 3± 20. 00) s,(101. 8± 50. 8) s;t=2. 939,P<0. 05),the difference were statistically significant. Compared with the model control group,the sugar water preference index of mice in the low,middle and high dose group of Hypericum perforatum extract increased ((61. 8±4. 7)%,(65. 2±4. 1)%,(62. 6±5. 6)%,t=-3. 005,5. 073,-2. 928,all P<0. 05),the swimming immobility time decreased ((47. 2±17. 9) s,(54. 8±50. 3) s,(61. 3±44. 2) s; t=2. 803,1. 921,1. 903,all P<0. 05). The results of Elisa showed that compared with the normal control group,the levels of serum DA and BDNF of mice in the model control group were significantly lower (t=3. 031,8. 507,all P<0. 05); com-pared with the model control group,the levels of serum DA of mice in the low dose and high dose group of Hypericum perforatum were significantly higher (t=5. 025,3. 414,P<0. 05),and the serum BDNF of mice in the high dose group of Hypericum perforatum was also significantly higher (t=6. 098,P<0. 05),the differ-ence was statistically significant. HE staining showed that compared with the normal control group,the neu-rons in CA3 area of hippocampus in the model control group mice were seriously damaged,suggesting the es-tablishment of the mouse model. Compared with the model control group,the atrophy and degeneration of hippocampal CA3 cells in the three dose groups were significantly reduced. The atrophy and deformation of hippocampal CA3 neurons in the low,middle and high dose groups of Hypericum perforatum extract were re-lieved. Conclusion HPLES have obvious improving and antidepressant effects on the depression model mice induced by chronic unpredictable stress. The above effects may be related to the improvement of serum DA,DBNF level and reduce neuronal damage in CA3 area.
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To study the protective effect of Xingnaojing Injection on early global brain ischemia-induced deep coma in rats. Methods: The deep coma model was induced by global brain ischemia by using four-vessel occlusion method in male SD rats. According to the body weight, the rats were randomly divided into 8 groups: a model control group, three different dose of Xingnaojing Injection (1.8, 3.6 and 5.4 mL.kg-1) groups, a Xingnaojing Injection (3.6 mL.kg-1) plus PI3K inhibitor group, a naloxone injection (0.04 mL.kg-1) group and a naloxone injection (0.04 mL.kg-1) plus Xingnaojing Injection (3.6 mL.kg-1) group (n=8 per group). In addition, eight animals served as the sham group were performed same operation with the model group excepting no blockage of the blood vessels. After the operation, three different doses of Xingnaojing Injection and/or naloxone injection were given intravenously once a day for three days. Ten μL PI3K inhibitor (LY294002, 10 mmol/L) was injected via anterior cerebral ventricle at once after global brain ischemia. The awakening time after the first drug treatment, the grasping power and the autonomous activity within 10 min after the last drug treatment were recorded. The levels of both dopamine (DA) and glutamate (Glu) in cerebrospinal fluid were detected by ELISA. The pathological changes were observed in brain tissue slices with HE staining and the protein levels of Akt/p-Akt and cAMP-response element binding protein (CREB)/p-CREB in hippocampus were detected by Western blotting. Results: Comparing with the model group, single administration of Xingnaojing Injection could significantly shorten the waking time (P<0.05) and continuous administration of Xingnaojing Injection for 3 d could increase grasping power, distance, frequency and duration of autonomous activities (P<0.05 or P<0.01) in the deep coma rat. Also, Xingnaojing Injection could inhibit these increases in neurotransmitters DA and Glu contents (P<0.05 or P<0.01), and improve pathological changes of hippocampal tissue. Xingnaojing Injection significantly induced protein phosphorylation of both Akt and CREB (P<0.05 or P<0.01); this effect was inhibited by PI3K inhibitor (P<0.05 or P<0.01). Moreover, the protective effects of naloxone on awakening time, grasping power, the autonomous activity and hippocampus damage in global brain ischemia-induced deep coma could be enhanced by joint use of Xingnaojing Injection (P<0.05 or P<0.01). Conclusion: Xingnaojing Injection could significantly improve deep coma induced by global brain ischemia in rat, which is related to inducing PI3K/Akt-dependent protein phosphorylation of CREB, and reducing hippocampal damage. The protective effect of Xingnaojing Injection is synergistically enhanced by naloxone.
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Animals , Male , Rats , Brain , Brain Ischemia , Coma , Drugs, Chinese Herbal , Phosphatidylinositol 3-Kinases , Rats, Sprague-DawleyABSTRACT
Postpartum depression(PPD)is one of the most common types of postpartum psychiatric syndromes. Because of the complex and changeable characteristics in PPD disease and the special period after childbirth, there are many clinical limitations in the study of this disease. Therefore,the preparation and establishment of a proper animal model closed to clinical and behavioral evaluation method plays an important role in study of its pathogenesis. This review mainly introduces the commonly used postpartum depression animal models and the behavioral evaluation method. It is hoped to provide a reference for further study of PPD pathogenesis and for the drug research and development.
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Objective To study the protective effect of shenfu injection on cerebral ischemia reperfusion injury in rats.Methods 120 male Sprague Dawley (SD) rats(320-350 g) were randomly divided into sham operation group,model control group,Nimodipine injection group,low,medium and high dose group of shenfu injection according to gender weight.20 males in each group were given medicine once a day for 7 days before operation.The cerebral ischemia model was established by thread embolization after 5 days of administration.In the sham operation group,the other operations were the same as those in the model group except for carotid artery ligation and thread insertion.After 24 hours of perfusion,the neurological score,abdominal aorta blood flow,malondialdehyde (MDA),superoxide dismutase (SOD) and glutathione (GHS) levels in brain tissues were measured.Triphenyltetrazolium chloride (TTC) staining was used to calculate the area of cerebral infarction and pathological examination of brain tissues.Results Compared with the model control group,the middle and high dosage of shenfu injection could obviously improve the nerve function and increase the percentage of cerebral infarction area (P ＜ 0.05);the high dosage group of shenfu injection could obviously decrease the whole blood viscosity (P ＜ 0.01);the middle and high dosage of shenfu injection could obviously reduce the level of MDA in rat brain tissue (P ＜ 0.01) while increasing the levels of SOD and GSH (P ＜0.01),finally could significantly improve the pathological changes of brain tissues such as mild swelling of nerve fibers,mild neuronal degeneration,inflammatory interstitial edema and inflammation.Conclusions Shenfu injection has obvious protective effect on cerebral ischemia reperfusion model in rats.
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Objective To establish a mouse model of circulating tumor cells (CTCs) by applying mouse hepatoma Hapa 1-6 cells.Methods 108 healthy male C57BL/6 mice were randomly divided into 3 groups according to their body weights.Hepa 1-6 cell suspension was intravenously injected to each mouse in the three groups at a concentration of 1×106,5×106 and 1×107/mL,0.2 mL per mouse,respectively.Blood samples were collected from the mice on the 1st,5th,9th,13th,17th and 21st days after tumor cell injection.The number,ratio and relative inhibition rate of CTCs were calculated in 20,000 nucleated cells.The mortality of mice was recorded.②80 male C57BL/6 mice were averaged into 2 groups according to their body weight: control and sorafenib tosylate groups.0.2 mL of Hepa 1-6 single cell suspension was injected to each mouse through the caudal vein at a concentration of 5×106/mL.The mice were gavaged with sorafenib tosylate (50 mg/kg) for 21 days and blood samples were collected at the 3rd,8th,15th,and 21st days for CTC assessment.Results For the 1×106/mL group,the CTC inhibition rate was 25.1%,18.1%,8.9%,4.4%,2.9% and 0.3% on the 1st,5th,9th,13th,17th and 21st days,respectively,and all the mice were alive.For the 5×106/mL group,the CTC inhibition rate was 40.4%,35.4%,15.4%,9.0%,6.6% and 4.1% on the 1st,5th,9th,13th,17th and 21st days,respectively,and all the mice were alive.For the 1×107/mL group,the CTC inhibition rate was 39.1% and 33.5% on the 1st and 5th days,respectively.Some mice died immediately after intravenous injection and all mice died within 7 days.②The relative clearance of CTCs was-7.5%,4.6%,55.3% and-94.5% on the 3rd,8th,15th and 21st days of sorafenib tosylate administration.Compared with the control group,there were significant differences among the three groups (P<0.05 or P<0.01).Conclusions A mouse model of circulating hepatoma cells has been established by intravenous injection of 0.2 mL of 5×106/mL mouse Hepa 1-6 cell suspension.This mouse model can be used for screening and evaluation of drugs for circulating tumor cell inhibition.
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Objective To establish animal models of functional dyspepsia with spleen deficiency and to compare the efficacy of different methods.Methods Rat models were established by iodoacetamide(IA)-treatment or combined with swimming.Appearance,body weight,food intake of the rats were observed,and serum motilin,cholecystokinin,lactate,gastrin content and urinary D-xylose excretion rates were detected to confirm whether the model of functional dyspepsia with spleen deficiency was established.Results The IA-treated rats had less food intake and a slower body weight gain.The IA-treated combined with swimming rats presented spleen-hypofunction symptoms,such as emaciation,hair dry and loose stools,their urinary D-xylose excretion rate,serum motilin,gastrin content were decreased,and serum cholecystokinin and lactate contents were increased significantly (P<0.05 for all).Conclusions All the three methods used in this study can result in symptoms of functional dyspepsia with spleen deficiency.However,IA-treatment combined with swimming models appear more close to spleen deficiency-like presentation,and the best model is the IA-treated combined with platform standing.
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Objective To investigate the influence of mannitol and glycerin injection (containing 15％ mannitol and 15％ glycerin) on experimental intracranial hypertension.Methods Rabbits were randomly divided into eight groups (n =8 rabbits/group):normal control group,model control group,mannitol-glycerol injection groups (2.5 ml/kg group,5 ml/kg group,and 10 ml/kg group),compound mannitol injection fluid group,20％ mannitol group,and 10％ glycerol-sodium chloride injection group.The continuous intravenous infusion of nitroglycerin [0.04 mg/(kg · min),10 min] on rabbits was used to establish intracranial hypertension model except the normal control group of animals,and effect of mannitol glycerol injection on it with a single intravenous injection was observed.Serum renal function,electrolytes and other indicators were tested.Results Intravenous infusion of mannitol glycerol injection (2.5 ml/kg,5 ml/kg,and 10 ml/kg) could significantly reduce rabbit nitroglycerin-induced intracranial hypertension,and dosedependent,with increasing dose reducing intracranial pressure could enhance(P ＜ 0.05).Mannitol glycerol injection (5 ml/kg) produced the same intracranial pressure compared to 20％ mannitol and compound mannitol injection,and maintained a long-time role.Conclusions Mannitol glycerin injection can significantly reduce intracranial pressure.Its intensity is the same as 20％ mannitol and compound mannitol injection,and maintains a longer intracranial pressure without significant renal dysfunction and electrolyte distnrhances.
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Objective To study the effect of sandalwood essential oil on isolated ileum smooth muscle of guinea pigs and the small intestine movement function of mice.Methods We used the experiment method of isolating ileum smooth muscle of guinea pigs and intestine propulsion of carbon ink in mice.We constructed the models of healthy mice,neostigminetrested mice and adrenaline-loaded mice.Results Sandalwood essential oil had an inhibitory effect on the spontaneous movement of guinea pigs isolated ileum and an antagonistic action on intestinal spasm caused by acetylcholine,histamine and barium chloride(P