Aim To investigate the effect of fenofibrate on focal cerebral ischemia injury in rats and its mechanism.Methods The rat model of global cerebral ischemia/reperfusion injury was established by bilateral common carotid arteries occlusion combined with hemorrhagic hypotension.Fenofibrate (33, 100, 300 mg·kg~(-1)) was intragastriclly administered 30 min before the operation, MK886 (6 mg·kg~(-1)) was given intraperitoneally 30 min before administration of fenofibrate (300 mg·kg~(-1)).Morris water maze was used to evaluate the ability of spatial learning and memory function.HE staining was used to observe pathological morphological changes of hippocampal neurons. NF-κBp65 expression was detected by immunohistochemistry, SOD activities and MDA contents were analyzed by biochemistry, and IL-1β, IL-6, IL-10, TNF-α levels were detected by ELISA.Results Fenofibrate remarkably improved the spatial learning and memory function, obviously prevented the hippocampal neurons from karyopycnosis and losing induced by I/R. Fenofibrate significantly blunted the increase of MDA, NF-κBp65, TNF-α, IL-1β, IL-6, and the decrease of IL-10 and SOD activities of I/R rats.Conclusions Fenofibrate has an obviously neuroprotective effect on global cerebral ischemia/reperfusion damage by activating PPARα.The anti-inflammation and antioxidative stress of fenofibrate may be involved in the protective mechanism.

Aim To establish primary cultured rat hip-pocampal neuron damage model induced by aluminum maltolate and study the effect of intervention for DP2 on primary cultured rat hippocampal neuron treated with aluminum overload. Methods The hippocampus was dissected out from fetal rat ( embryonic 18 d ) . After being cultured for 7 d, the hippocampal neuron was treated with Al( malt) 3 to establish the model of prima-ry cultured rat hippocampal neuron damage and mean-while treated with DP2 agonist DK-PGD2 and DP2 an-tagonist CAY10471, respectively. After treatment for 24 h, the cell viability was measured by MTT and LDH, Ca2+ fluorescence intensity. Neuronal pathomor-phology was observed by HE staining. Results The purity of hippocampal neuron was more than 95%. Compared with the control group, the number of hipp-ocampal neurons was reduced and neurons became chromatic agglutination and karyopyknosis in aluminum overload group. Treatment of aluminum caused a sig-nificant decrease in MTT value ( P<0. 01 ) and an in-crease in the LDH leakage rate (P<0. 01). The Ca2+fluorescence intensity significantly increased ( P <0. 01 ) in aluminum overload group. Compared with that of the aluminum overload group, treatment of DK-PGD2 , a selective DP2 agonist, significantly aggravated the primary cultured rat hippocampal neuron injury caused by aluminum overload accompanied with the significant decrease of MTT value ( P <0. 01 , P <0. 05 ) and an increase of the LDH leakage rate ( P<0. 01), significant increase of Ca2+ fluorescence inten-sity of neuron. Treatment of CAY10471, a selective DP2 antagonist, had opposite effects of DK-PGD2 . Conclusion The activation of DP2 can increase hipp-ocampal neural susceptibility to aluminum overload.

OBJECTIVE:To investigate the protective effect of meloxicam on aluminum overload-inducing damage of hippocampal neuron.METHODS:Primary hippocampal neuron attained from new born SD rats was cultured for 7 days.There were 5 groups e.g blank control group (200 ?mol?L-1 NaCl),aluminum model group (200 ?mol?L-1 AlCl3) and meloxicam low-dose (10-8 mol?L-1),medium-dose (10-7 mol?L-1) and high-dose (10-6 mol?L-1) groups.HE staining was used to observe the change of neuronal morphology.The optical densities of cells were measured.The activities of SOD,leakage of LDH and content of MDA were also detected.RESULTS:As compared with control group,the optical density of cells and activity of SOD were decreased and leakage of LDH and content of MDA were increased (P

AIM:To study the effects of domestic glimepiride(Gli) on blood sugar,glucose tolerance and release of insulin in rabbits and rats METHODS:Taken the changes of blood sugar level and glucose tolerance before and after giving drug as parameters,the hypoglycemic effect of Gli was observed in rabbits and rats RESULTS:Gli dose-dependly decreased the levels of blood glucose in rats with a decrease of 23% in high-dose group and seemed to be similar to glibenclamide in potency of lowering blood sugar Gli increased release of insulin by 40%～70% in rats and rabbits and was twice as potent as glibenclamide;Glucose tolerance test showed that Gli could restrain the rising of blood glucose at 30 min and 60 min after glucose was administrated ig in rabbits Time-response relation displayed that blood glucose began to drop 30 min after Gli 1 0mg/kg administered and the levels of blood glucose dropped by 40% 3 h later CONCLUSION:The domestic Gli has similar effects to glibenclamide on lowering blood sugar However,its effect on lowering blood sugar seems to be quicker,shorter and more moderate than that of glibenclamide

Aim To study the protective effect of caffeic acid on brain damage induced by chronic aluminum overload in rats.Methods The brain injury model of rats was established via intragastric administration of aluminum gluconate(element aluminum 200 mg?kg-1) once a day,5 d a week for 20 weeks.The 5-LO inhibitor caffeic acid(30 mg?kg-1,10 mg?kg-1) was intragastrically administered 1 h after aluminum administration.Pathomorphological changes of hippocampal neuron and the spatial learning and memory function were observed.The MAO-B,AChE and SOD activities,and the MDA contents of brain tissue in rats were measured.Results Chronic aluminum overload could markedly induce spatial learning and memory function impairment,and hippocampal neuronal injury in rats.The MAO-B and AChE activities,and the MDA content significantly increased,while SOD activities significantly decreased in chronic aluminum overload rats.The administration of the caffeic acid can significantly prevent rats from learning and memory function impairments and hippocampal neuronal death,and blunted the decrease of SOD activities and increased MDA contents induced by chronic aluminum overload in rats.Caffeic acid also obviously decreased the MAO-B activities and AChE activities of chronic aluminum overload rats.Conclusion Administration of caffeic acid can prevent the rat brain from damage induced by chronic aluminum overload.

Objective To study the neurotoxicity of chronic aluminum overload and the protective effects of nimodipine in rats.Methods The brain damage models of rats were established via intragastric administration of aluminum gluconate(element aluminum 400 mg/kg)once a day,5 d/week for 12 weeks.The step-down test and programmed Morris water maze test were used to evaluate the changes of learning and memory functions of rats.Pathomorphological changes of hippocampi of rats were observed.The activities of SOD,ChAT,AchE,MAO-B and the contents of MDA of brain tissue in rats were also measured.Nimodipine(80 mg/kg)were intragastrically administered 4 h after aluminum administration every time for 12 weeks.Results Chronic aluminum administration induced the impairment of avoidance learning and memory ability and spatial oriental ability.Consistent with the behavioral changes,neuronal death in the hippocampi,decreased activities of SOD and ChAT,increased content of MDA,and increased activity of MAO-B and AchE were detected in the aluminum-overload mice.The administration of nimodipine could significantly protect rats from the brain damage,and behavioral and biochemical changes above caused by aluminum overload were in a dose-dependent manner.Conclusion These results suggest that changes of cellular calcium overload and oxide stress and MAO-B activities are involved in pathophysiological mechanisms of brain injury induced by chronic aluminum overload.Nimodipine has a protective effect on neurotoxicity of chronic aluminum overload.

Aim In order to study the protective effect of caffeic acid on damage induced by aluminum-overload in primary cultured rat hippocampal neuron.Methods Primary cell cultures were obtained from the cerebral hippocampus of Newly born SD rats within 24 h.On the d 7 of neuronal culture, the immunohistory of NSE was used to identify the purity of neuron.There were 5 experimental groups,NaCl(200 μmol·L~(-1))-treated group, AlCl_3-treated group(200 μmol·L~(-1)),and aluminum+caffeic acid(10~(-6) mol·L~(-1),10~(-7) mol·L~(-1) and 10~(-8) mol·L~(-1))-treated groups. HE staining was used to observe the change of neuronal pathomorphology. The cell viability was measured by MTT assay. SOD activity, LDH leakage and MDA contents were also detected.Results The purity of neurons was more than 95%. Aluminum administration induced loss of neurons and damage to dendrite and axon.Compared with that of the control group,the decreased viability of neurons,increased leakage of LDH, decreased activity of SOD and increased contents of MDA were observed in aluminum-treated groups.Compared with that of the model group, the administration of Caffeic acid could significantly blunt the death of the primary cultured hippocampal neurons, and blunt the decrease of neuronal viability and SOD activity and the increase of LDH leakage and MDA contents.Conclusions These results suggest that caffeic acid has an obvious protective effect against neuronal damage induced by aluminum overload in primary cultured neurons. The mechanism of protection might involve the anti-inflammation and anti-oxidative effects of caffeic acid.

OBJECTIVE:To evaluate the preventive and therapeutic effects of extract of Curcuma on experimental hyper?lipidemia models in rats and rabbits.METHODS:Hyperlipidemia models of healthy rats and rabbits,fed on a forage containing cholesterol,fat and etc,were established.TG,TC,LDL,HDL and LDL/HDL in serum of animals were measured.RESULTS:The preventive administration of extract of Curcuma could significantly reduce the serum TC,LDL,LDL/HDL and increase serum HDL in hyperlipidemic rats in a dose-dependent manner.Its hypolipidemic action was stronger than that of positive contrast agent lovastatin.The serum levels of TC,TG,LDL and HDL not of LDL/HDL obviously decreased in hyperlipidemic rabbits after either preventive or therapeutic administration and its hypolipidemic action was weaker than that of positive con?trast agent lovastatin.CONCLUSION:Extract of Curcuma could obviouly reduce hyperlipidemic in rats and rabbits.Its action is stronger than that of lovastatin in rats,but weaker in rabbits.

Aim To investigate the effects of heme oxygenase-1(HO-1) on brain damage due to cerebral ischemia/reperfusion.Methods 120 male mice were divided into four groups randomly and the cerebral ischemia/reperfusion(I/R) model was established through drawing out and reperfusing 40% of the whole blood volume in combination with clamping the carotid arteries for 20 min after anesthesia with 40 g?L-1chloral hydrate(400 mg?kg-1 ip).The mice were intracerebraventricularly(icv) injected with 3(l of150 ?mol?L-1 hemin,150 ?mol?L-1 ZnPPIX,or artificial cerebrospinal fluid(ACSF),respectively 16 h before the model established.Sham operation group only received anesthesia and operation without I/R and icv injection.The hippocampal HO activity and cerebral cortex xanthine oxidase(XO) activity,the levels of malonaldehyde(MDA) and reactive oxygen species(ROS),hippocampal neuron apoptosis,and hippocampal HO-1 expression were determined by spectrophotometer,TUNEL method,and Western blot,respectively.Results The increased hippocampal HO-1 expression and HO activity,decreased XO activity,MDA and ROS levels,and diminished hippocampal apoptosis were observed in the hemin group,compared with ACSF group(P0.05),but inhibited the activity of HO with the elevation of XO activity,MDA and ROS levels,as well as cellular apoptosis(vs ACSF,P