Background and aims: COX-2-selective inhibitors have been associated with an increased risk of cardiovascular complications, and their impact on atherosclerosis ( AS) remains controversial. The proinflammatory COX-2 and 5-LO pathways both play essential roles in AS and related cardiovascular diseases. Previous clinical studies have provided evidence of the ability of COX-2-selective inhibitors to shunt AA metabolism from the COX-2 pathway to the 5-LO pathway. In this study, the effects of celecoxib, a selective COX-2 inhibitor, on AS and the COX-2 and 5-LO pathways were investigated in vivo and in vitro. Methods: Male ApoE(-/-) mice fed a western-type diet for 18 weeks and cultured mouse RAW264.7 macrophages stimulated with 1 mu g/mL LPS for 24 h were used in this study. Results: In ApoE(-/-) mice, intragastric administration of celecoxib ( 80 mg/kg/d) for 18 weeks significantly increased aortic atherosclerotic lesion area but had no effect on hyperlipidemia. In addition, celecoxib significantly lowered TNF-a and PGE2 levels but increased both LTB4 and CysLTs levels in aortic tissues. In LPS-stimulated RAW264.7 macrophages, pretreatment with 8 mu mol/L celecoxib for 1 h significantly lowered the TNF-a, NO, and PGE2 levels but increased the LTB4 and CysLTs levels. Celecoxib also decreased the protein and mRNA expression of COX-2 but increased the expression of 5-LO and LTC4S in both ApoE(-/-) mouse aortic tissues and LPSstimulated RAW264.7 macrophages. Conclusion: The COX-2-selective inhibitor celecoxib can aggravate atherogenesis, an effect that may be related to upregulation of LTs via a 5-LO pathway shunt.

Objective:To study the protective effect of dihydromyricetin (DMY) on acute cerebral hypoxiaischemia in mice.Methods:Male Kuming mice were randomly divided into control or sham group,high-and low-dose DMY group,ginaton group and model group.The mice in the high-and low-dose DMY group were administered 500 mg/kg and 250 mg/kg DMY respectively via intragastric gavage for 10 days.At 1 h after the last administration,the gasping time and gasping number of beheaded mice,survival time,oxygen consumption ratio in hypoxia tolerance mice,and survival time in bilateral carotid artery ligation (BCAO) mice were observed.Results:High-and low-dose DMY could significantly increased the gasping time and gasping number of beheaded mice,prolonged the oxygen consumption ratio of hypoxia tolerance mice and the survival time of BCAO mice.High-dos of DMY could also prolong the surviving time of hypoxia tolerance mice.Conclusion:DMY exerted a protective effect on acute cerebral hypoxia-ischemia in mice.

目的 建立脂多糖(LPS)诱导的RAW 264.7巨噬细胞炎症模型,探讨塞来昔布对其分泌炎症因子的影响.方法 培养小鼠RAW 264.7巨噬细胞,采用1μg/ml的LPS刺激小鼠RAW 264.7巨噬细胞24 h后,收集细胞培养基,采用Griess法测定一氧化氮(NO)及ELISA法测定肿瘤坏死因子α(TNF-α)、前列腺素E2(PGE2)的含量,从而建立LPS诱导的RAW 264.7巨噬细胞炎症模型.采用MTT法检测塞来昔布对LPS刺激的RAW 264.7巨噬细胞的毒性作用后,选用8.00 μmol/L塞来昔布预处理细胞1h,再加入1μg/ml LPS刺激细胞24 h,收集细胞培养基,测定培养基中炎症因子NO、TNF-α及PGE2的含量.结果 1μg/ml的LPS刺激RAW 264.7巨噬细胞24 h后,细胞形态出现明显变形,细胞培养基中炎症因子NO及TNF-α、PGE2含量均较正常对照组明显增高(P＜0.01).与DMSO溶剂对照组相比,8.00μmol/L塞来昔布组能明显抑制LPS诱导的RAW 264.7巨噬细胞炎性因子NO、TNF-α及PGE2的释放(均P＜0.01).结论 成功建立LPS诱导的RAW 264.7巨噬细胞炎症模型,塞来昔布可明显抑制其炎症因子NO、TNF-α及PGE2的分泌.

Objective To study the acute and subchronic toxicity of Podocarpus macrophyllus fruit and evaluate its safety.Methods Maximum dosage method was adopted for acute toxicity experiment.The mice were administrated with the receptacle juice (with mass concentration of 200％) of Podocarpus macrophyllus fruit by intragastric infusion twice a day with total dosage of 160.0 g/(kg · d).After being administrated,the mice were observed for 14 days.In subchronic toxicity test,rats were randomly divided into three groups.The rats of treatment groups were given the juice(with mass concentration of 200％) by oral garage with dosage of 20 g/kg and 10 g/kg for 90 days continuously.And the rats of control group were given distilled water by oral garage.The routine blood test,serum biochemical index determinations,and histopathological examination were carried out at the end of the experiment.The important organs were weighed to calculate the organ/body ratios.Results During the experiments,no toxic effects and death were observed in each group.The index determination and histopathological results showed no statistical significance on the difference between the treatment and control group(P ＞0.05).Histopathological findings did not correlate with histopathological changes in the subjects.Conclusion In this experiment,receptacle juice of Podocarpus macrophyllus fruit shows no acute and subchronic toxicity to animals.It can be used as raw materials for food development and utilization.

Objective To study the influences of dihydromyricetin ( DMY) on inflammatory reaction induced by fo-cal cerebral ischemia-reperfusion ( I/R) injury in mice.Methods Male Kunming mice were randomly divided into 3 groups:sham group,I/R group and DMY 500 mg/kg group.Mice model of middle cerebral artery occlusion (MCAO,3 h)/reperfusion (24 h) model was established by the improved intraluminal filament technique .Drugs were given orally 10 d (once a day ) before the surgery ,1 h before ischemia and 12 h after reperfusion .After reperfusion for 24 h,the expressions of ionized calcium binding adaptor molecule-1( Iba1) and 5-LOX in mice brain were assessed by immunohistochemistry;the contents of TNF-αand 5-LOX metabolites ( LTB4 and CysLTs ) in ischemic brain tissue were detected by ELISA .Results Compared with the I/R group,DMY at 500 mg/kg could obviously inhibit the activation of microglia ,lower the level of TNF-α,and reduce the expression of 5-LOX and the production of LTB4 and CysLTs (P<0.05或P<0.01).Con clusion DMY reduces inflammatory reaction induced by focal cerebral I /R injury,which might be associated with its inhibition on 5-LOX.

目的 比较小鼠脑缺血后星形胶质细胞和小胶质细胞的活化规律.方法 采用改良线栓法制备小鼠大脑中动脉阻塞再灌注局灶性脑缺血损伤模型.昆明小鼠48只,随机分为假手术组24只和脑缺血组24只.脑缺血组缺血3h后再分为再灌注1、3、7和14d,每个时间点6只.再灌注结束后,取脑作HE染色观察脑组织病理改变,免疫组织化学染色法检测星形胶质细胞胶质纤维酸性蛋白(GFAP)和小胶质细胞离子钙接头蛋白1(Iba1)的表达.结果 与缺血再灌注1d比较,脑缺血组缺血再灌注3、7、14d皮质缺血周边区的GFAP阳性产物显著增加[(699.22±160.82)μm2/HP,(1817.97±290.88)μm2/HP,(2831.64±481.38) μm2/HP vs (33.13±7.45) μm2/HP,P＜0.01].脑缺血组缺血再灌注1d皮质缺血周边区出现以“分支状”为主的Ibal阳性小胶质细胞,3、7d活化的小胶质细胞显著增多并表现为“灌木样”细胞,14d后活化小胶质细胞呈现“阿米巴样”细胞.结论 脑缺血再灌注损伤时,小胶质细胞和星形胶质细胞均出现活化,但小胶质细胞活化出现得更早;星形胶质细胞活化只出现在缺血周边区,而活化的小胶质细胞可从缺血周边区向缺血中央区迁移.

Objective To determine the polysaccharides content of fruit from Podocarpus macrophyllus. Methods The ultrasonic-assisted extraction method was used to extract polysaccharides from the fruit of Podocarpus macrophyllus and the polysaccharides content was determined by sulphuric acid-phenol colorimetric method, with glucose as reference substance. The UV detection wavelength was 490 nm. Results Glucose absorbance showed a good linear relationship with the content in the range of 20-100 μg/mL. The regression equation is Y=0. 008 0 X-0. 0158, r=0. 998 0 ( n=5 ) , and the average recovery rate was 101. 64%, RSD=4. 77%( n=6 ) . The aver-age content of polysaccharides in Podocarpus macrophyllus is 4. 74 mg/g ( according to glucose ) . Conclusion This determination method is simple to be operated, with good reproducibility, and the results are accurate and reliable, which can be used to determine the polysaccharides content of Podocarpus macrophyllus.