������������ضԴ����ļ����˵ı�������

??OBJECTIVE To discuss the effect and mechanism of cinepazide maleate (CM) on myocardial injured rats induced by isoproterenol (Iso). METHODS Fifty male and female rats were divided into normal group, model group, the low and the high dose group of the CM, and captopril (Cap)positive control group. The rat model of myocardial injury was established by subcutaneous injection of Iso (5 mg??kg^-1??d^-1)for 7 d, rats in treatment group were given intraperitoneal injection of CM on the second day (1.5,3 mg??kg^-1??d^-1), rats in positive control group were given intragastric administration of Cap(10 mg??kg^-1??d^-1), and rats in normal group and model group were given intraperitoneal injection of normal saline in the same volume, for 14 d. The rats in each group were tested before and after treatment by three times of running endurance test. After stopping drug all rats were anesthetized for measuring the electrocardiogram (ECG), then taken blood for measuring the activities of serum SOD, LDH and CK, and taken hearts for measuring heart weight index (HWI), left ventricular mass index (LHWI), the contents of myocardial hydroxyproline (Hyp)and MDA, and observing the morphological changes of myocardial tissue by HE staining. RESULTS Compared with rats in normal group, rats in model group showed endurance value decrease, ECG abnormalities (arrhythmia and myocardial ischemia in waveform), increased HWI, LHWI (P<0.01), myocardial Hyp content, myocardial MDA level, and the level of serum LDH and CK, and reduced the serum SOD activity (P<0.05 or P<0.01). Compared with model group, CM could significantly increase endurance value, improve abnormal phenomenon of ECG, lower the HWI, LHWI, myocardial Hyp content, myocardial MDA level, and serum LDH and CK levels were lower, and serum SOD activity increased, especially in high dose group of CM (P<0.01). HE staining showed in the model group rat ventricular remodeling, myocardial rupture, a large number of collagen fibers, in the treatment group, ventricular remodeling and myocardial fibrosis were significantly improved. CONCLUSION Cinepazide maleate has protective effect on myocardial injury of rats induced by Iso.     

D-��������˥�ϴ������ڴٺ�ϸ�������ر���µ�����ػƵ���ת����

??OBJECTIVE To observe the change of EPO in brain of aging rat induced by D-galactose(D-gal) and the EPO-based antiaging of the water extract of Radix Rehmanniae Preparata(WERRP). METHODS D-gal-treated groups were received subcutaneous injection of D-gal at dose of 50, 150 and 250 mg??kg^-1 daily for 8 weeks to imitate an aging model that was induced by oxidative stress. After the detection of EPO in hippocampus, the 150 mg??kg^-1 D-gal group was chose as the aging model. In addition the WERRP-treated group and vehicle group was set. The WERRP-treated group was given WERRP oral gavage at a dose of 4 g??kg^-1 daily starting from the 5th week. Morris water maze (MWM) test was used to assess the spatial learning and memory. SOD, MDA and ??-galactosidase in brain were examined by Assay Kits. Finally, EPO, EPOR, and HIF-2?? in hippocampus were determined by immunohistochemistry and Western blot. RESULTS D-gal-treated group showed significant longer latency to platform and less times of cross the platform(P<0.05) in MWM. After treated with D-gal, SOD was drastically decreased and MDA and ??-galactosidase were remarkably increased in brains compared with vehicle (0.9% saline)-treated rats (P<0.01). In addition, the expression of EPO,EPOR and HIF-2?? were significantly decreased in the brains of D-gal-treated rats compared with vehicle-treated rats. Meanwhile, there was a negative correlation between EPOR and MDA in content. Interestingly, WERRP-treated rats showed significant improvement of spatial learning and memory, decrease of oxidative stress and enhancement of EPO/EPOR in the brain compared with 150 mg??kg^-1 D-gal-treated rat(P<0.05). CONCLUSION The aging rats induced by D-gal show a significant decline of EPO in brain which indicate the decrease of brain EPO in aging is related to the increase of oxidative stress. That WERRP reverses the decline of the EPO expression in aging model may be the underlying mechanism of the role of anti-aging of WERRP.     

������Ƭ�ڼ����ļ���������Ѫ�������е����ü������о�

??OBJECTIVE To investigate the influence and mechanism of different doses of Yangxinshi on infarction region angiogenesis of Wistar rats after acute myocardial infarction. METHODS Sixty healthy male Wistar rats were randomly divided into five groups, named as follow:group A: rosuvastatin group (0.75 mg??kg^-1??d^-1), group B: high-dose Yangxinshi(0.27 g??kg^-1??d^-1),group C:mid-dose Yangxinshi group (0.18 g??kg^-1??d^-1),group D: Low-dose Yangxinshi group (0.09 g??kg^-1??d^-1),group E:saline control group. A, B, C, D group was respectively given the drug by gavage, group E received normal saline by gavage. The models of acute myocardial infarction can be established in the forth week . After continued drugs for 4 weeks, rats were killed before detected blood biochemicalindexes such as blood lipids, liver and kidney function. Myocardial tissue was sliced and stained infarcted myocardium by HE to observe the pathological changes, also extract ischemic and infarct myocardium tissue protein and test VEGF protein expression with immunohistochemistry. RESULTS Myocardial tissue HE staining were observed a lot of survival island cardiomyocytes and neonatal thin-walled capillaries in four treatment groups , however,control group exist less normal cardiomyocytes and capillaries mainly disappear. Immunohistochemistry RESULTS showed high-doses of Yangxinshi group express higher VEGF protein compared with mid-dose group, low-dose group and control group, the difference was statistically significant (P<0.05), VEGF protein expression was significantly increased the in mid-dose and high-dose Yangxinshi groups than rosuvastatin group, the difference was statistically significant (P<0.05). CONCLUSION Yangxinshi promote production of VEGF protein and angiogenesis of ischemic myocardium ,in addition its role and its dose is positive correlated. VEGF protein expression was significantly increased the in mid-dose and high-dose Yangxinshi groups than rosuvastatin group, the difference is statistically significant (P<0.05).     

޺�������ﱽ�Ҵ��նԸ�ԭ�������˵ĸ������ü������о�

??OBJECTIVE To investigate the ameliorated effect and mechanisms of phenylethanoid glycosides from Pedicularis muscicola Maxim on high altitude memory impairment. METHODS After successfully trained in the 8-arms radial maze, fifty Wistar rats were randomly divided into normoxic control group, hypoxia group, phenylethanoid glycosides 50, 200 and 400 mg??kg^-1 groups(given corresponding dose). Normoxic control and hypoxia groups were administered with distilled water for a week.When drug delivery in the fourth day, hypoxia and phenylethanoid glycosides groups rats were exposed to a simulated of 7 500 m in a specially designed animal decompression chamber. Eight arms radial maze was used to measure spatial memory, HE stained was used to observe the cell morphology in brain tissue and biochemical technique was used to detect the content of MDA and ROS and enzymatic activity of GSH and SOD in brain tissue and serum. RESULTS Compared with the normoxic control group, for hypoxia group rats, WME, RWE and TE were respectively increased by 800%, 71%, and 127.1%(P??0.01) and neuron damage was significantly increased, the enzymatic activity of GSH and SOD were respectively decreased by 60.9% and 18.11%(P<0.05, P<0.01) in brain tissue and plasma while the content of MDA was increased in brain tissueby 74.8% (P<0.01). Compared with the hypoxia group, for phenylethanoid glycosides 200, 400 mg??kg^-1 groups rats, WME,RWE,TE were respectively decreased by 68.44%,63.11%;33.14%,25.34% and 43.91%, 36.72% (P??0.05, P??0.01) and neuron damage was significantly decreased, the enzymatic activity of GSH were respectively increased by 219.76%, 180.75% and 32.81%, 24.10% (P<0.05, P<0.01) and the enzymatic activity of SOD were respectively increased by 9.57%, 13.88% and 15.41%, 15.45% (P<0.05) in brain tissue and plasma,while the content of MDA in plasma were respectively decreased by 42.73%, 42.73% (P<0.01) and MDA and ROS in brain tissue were respectively decreased by 61.71%, 42.79% and 40.76%, 23.53% (P<0.01); for phenylethanoid glycosides 50 mg??kg^-1 group rats, the corresponding indicators had been ameliorated, but there was no significant difference.CONCLUSION Phenylethanoid glycosides of Pedicularis muscicola Maxim can ameliorate high altitude memory impairment, which its involved mechanism may be antioxidant stress and inhibition on cell damage.     

�����նԼ�����ȱѪС���񾭱������ü������屣�����Ƶ��о�

??OBJECTIVE To observe the neuro-protective effects of harpagide on acute cerebral ischemic injury in mice and its mechanism involving mitochondria. METHODS Acute cerebral ischemia were achieved by operation of MCAO in the left brain, random allocation was taken to divide ICR mice into sham group, model group, nimodipine group and harpagide(5, 10, 15 mg??kg^-1) groups. Mice were intraperitoneal injected harpagide immediately after surgery. Nerve function score, content of brain water, brain index and the common changes of brain pathological structure in HE staining were measured; Ability of mitochondria?? Ca²⁺-Mg²⁺-ATPase and protein expression level of caspase-3 in the MCAO mice?? brains was determined; Ultrastructure change of mitochondria under the TEM was observed. RESULTS Compared with model group, the harpagide groups could decreased the nerve function score, the content of brain water, brain index and the volume of ischemia in mice with different degrees in MCAO mice(P<0.05,P<0.01); 10 mg??kg^-1 of harpagide could increased the activity of Ca²⁺-Mg²⁺-ATPase obviously(P<0.01); And significantly decreased the protein expression level of caspase-3(P<0.01); harpagide groups could protect the pathogeny structure and the ultrastructure of mitochondria with different degrees in MCAO mice, decrease edema of mitochondria obviously. CONCLUSION Harpagide could obviously protect acute cerebral ischemia in mice, its therapeutical effects are approached to protecting the activity of brain mitochondria and decreasing protein expression level of caspase-3.     

��-����ø���Ƽ�DAPT����֢�յ�����С��δ�����԰�������Ӱ��

??OBJECTIVE To investigate the effect of ??-secretase inhibitor DAPT in inflammation-induced brain white matter injury in neonatal mice.METHODS Sixty C57BL/10J neonatal mice are randomly divided into control group, control+DAPT (10 mg??kg^-1) group, inflammation (LPS) group, LPS+DAPT group (inflammation exposure after 10 mg??kg^-1 DAPT treatment). All neonatal mice were killed and brain was removed to the following observation and detection:at P5, the mRNA expression variation of IL-1??, IL-8,TNF-??,Hes1 and NICD by Real-time PCR methods. Oligodendrocytes were identified by immunofluorescence staining. Myelin basic protein (MBP) protein expression was detected by Western blot assay.RESULTS LPS group showed brain injury characterized by inhibition of brain development. There were significant differences in mRNA expression of IL-1??, IL-8, TNF-??, Hes1 and NICD between LPS+DAPT group and LPS group (P<0.05), and the mRNA expression of IL-1??, IL-8,TNF-??,Hes1 and NICD in inflammation-treated were significantly increased than control group (P<0.05). The results showed more expression of MBP in LPS+DAPT group compared with LPS group (P<0.05). Compared with the blank control group, which was obviously decreased after 48 h of inflammation (P<0.05).CONCLUSION Inflammation leads to abnormal of notch signal expression in neonatal mice, and which is shows inflammation involved in brain damage.Its mechanism is probably associated with the maturation of oligodendrocytes.     

����������׻����������⿹�Ҹβ���ʵ���о�

??OBJECTIVE To evaluate the anti-hepatitis B virus (HBV) activity of herpetrione nanosuspension (PEDX-NS) both in vitro and in vivo. METHODS HepG2 2.2.15 cells and duck hepatitis B virus (DHBV) infected ducks as in vitro and in vivo models were used to compare the anti-HBV activity of PEDX-NS and PEDX coarse suspension (PEDX-CS). RESULTS In the HepG2 2.2.15 cell, PEDX-NS effectively suppressed the secretion of the HBV antigens (HBsAg and HBeAg) in a dose-dependent manner with significant difference from PEDX-CS (P<0.05 or P<0.01). In the in vivo evaluation, PEDX-NS with high dose (100 mg??kg^-1) and middle dose (60 mg??kg^-1) significantly reduced the serum HBV DNA level (P<0.05 or P<0.01) and the effect was better than that of PEDX-CS (P<0.05 or P<0.01). CONCLUSION The result revealed that PEDX-NS exhibits anti-HBV activity both in vitro and in vivo and its effect was superior to that of PEDX-CS. The mechanism is probably that the small particle size of PEDX-NS provides a large specific surface area that resulted in better absorption in vivo, thus enhancing its anti-HBV activity.
     

��֥�����Ͷ�����С����Ϊѧ��Ӱ�켰�����������

??OBJECTIVE To study the effects of ganoderma spore oil(GSO) on behavior of the mice with chronic unpredictable mild stress (CUMS) and its possible neurophysiology mechanisms. METHODS Thirteen different kinds of chronic unpredictable mild stress were given to the male BALB/C mice for establishing the mouse model of depression. The mice were treated with GSO at 3 doses (850, 283, 141.5 mg??kg^{- 1}??d^-1) or vehicle [(oil) or fluoxetine (10 mg??kg^{- 1}??d^-1)] by oral administration from the 3rd week. After 2 weeks administration, the mice was evaluated by behavioral tests, and the contents of hippocampal glutamate (GLU) and ??-amino butyric acid (GABA) were analyzed by reversed phase high performance liquid chromatography (RP-HPLC). The contents of hippocampal brain derived neurotrophic factor (BDNF) were measured by ELISA kit. RESULTS Compared with model group, GSO increased the body weight, sucrose preference rate and open field test score, shortened the immobility time in the tails suspension test and forced swimming test in the depression mice (P<0.05 or P<0.01). Meanwhile, GSO significantly decreased the contents of GLU (P < 0.01 ) and increased the contents of BDNF(P<0.01), and the contents of GABA did not changes (P>0.05) in the hippocampus. CONCLUSION GSO shows obvious anti-depressant effect on depressant model mice. The antidepressant effect of GSO may be related to decreasing GLU contents and increasing BDNF contents.