��ζ�Ӽ��ض����Բ���Ԥ֪�ºʹ̼�����������Ϊ��Ӱ�켰�����

??OBJECTIVE To investigate the anti-depressant effect of schisandrin A in rats with depression caused by chronic unpredictable mild stress(CUMS)as well as the relevant mechanism. METHODS The depression-like rat model using CUMS was established. Rats were randomly divided into control, CUMS model, CUMS+fluoxetine (10 mg??kg^-1)and CUMS + schisandrin A (25, 50, 100 mg??kg^-1)groups. Drugs or vehicle were administrated after stress procedures for 21 d. Open-field test (OFT), sucrose preference tests (SPT)and forced swim test (FST)were used to evaluate the anti-depressant effects of schisandrin A. The reactive oxygen species (ROS)and prostaglandin E₂ (PGE₂) level as well as superoxide dismutase (SOD) and catalase (CAT)activities in hippocampus were determined by ELISA methods. IL-1??, TNF-??, and IL-10 expression were measured by real time qPCR and Western blot analysis. RESULTS Behavioral test indicated that crossing score and rearing score in OFT and sucrose preference index in SPT of model group were significantly lower than control group (P<0.01), while immobility time in FST was significantly increased (P<0.01). Compared with those in control group, the ROS and PGE₂ level increased significantly (P<0.01), SOD and CAT activities decreased significantly (P< 0.01),the mRNA and protein level of IL-1??, TNF-??, and IL-10 were increased significantly (P<0.05 or P<0.01)in rats of CUMS. CONCLUSION Schisandrin A and fluoxetine could ameliorate those changes induced by CUMS. Schisandrin A could improve the depression-like behaviors of rats induced by CUMS, of which the mechanism might involve the antioxidant and anti-inflammatory effects.     

޺�������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.     

άҩ��Ҷ�����ܻ�ͪ��Ѫ�ܽ����آ��յ��Ĵ����ļ�ϸ���ʴ��Ӱ��

??OBJECTIVE To observe the effect of Dracocephalum heterophyllum flavonoids(DHBF) of Uygur Medicine on cardiomyocyte hypertrophy, which were induced by angiotensin ??(Ang??), and it could provide a basis for further study to the mechanism. METHODS SD rats,0-3 d of age, neonatal rat myocardial cells cultured in vitro, the experiment was divided into control group, Ang??(1 ??mol??L^-1)group, different concentrations of DHBF(10, 25, 50 ??mol??L^-1)+Ang??(1 ??mol??L^-1) groups, cardiomyocyte hypertrophy were induced by Ang?? 1 ??mol??L^-1 and was intervened using DHBF respectively, CCK-8 method was used to observe the activity of myocardial cells,RT-PCR technique was used to detect the expression of m RNA of cardiac hypertrophy gene atrial natriuretic peptide(ANP) and brain natriuretic peptide(BNP),the internal factor was glyceraldehyde-3-phosphate dehydrogenase(GAPDH) .Confocal laser scanning was used to detect the surface area of myocardial cell was [Ca²⁺]_i;the activity of Ca²⁺-ATP was measured by the enzymatic reaction of fragmentation cell; the concentration of NO and the activity of NOS were determined by colorimetry. RESULTS Compared with the control group, the activity of myocardial cell was(85%??5%) in the Ang??group,which was increased significantly after it was dealed with DHBF and Ang??(P<0.05);RT-PCR results showed the expression of mRNA of ANP and BNP were increased by using Ang??, which were lower by using DHBF and Ang??. The surface area of myocardial cell were increased by using Ang??, which could be reversed by using DHBF and Ang??. Confocal laser scanning showed the concentration of[Ca²⁺]_i was increased by using Ang??,but which was lower significantly by using DHBF and Ang??(P<0.05). The enzymatic reaction of fragmentation cell results showed the activity of Ca²⁺-ATP was decreased by using Ang??, but which was increased significantly by using DHBF and Ang??(P<0.05). Colorimetry results showed the concentration of NO and the activity of NOS were decreased by using Ang??, but which was increased significantly by using DHBF and Ang??(P<0.05). CONCLUSION DHBF can improve the activity of hypertrophy cardiomyocytes which were induced by ang??, downregulate expression of mRNA of ANP and BNP, reduce surface area of cardiomyocytes induced by Ang??,the mechanism of action may be related to promoting the release of NO, regulating the concentration of[Ca²⁺]_i and the activity of Ca²⁺-ATP.     

������ͪ�Դ���ǰ������������������

??OBJECTIVE To investigate the inhibitory effect and possible mechanisms of puerariae isoflavone(PI) on prostatic hyperplasia induced by testosterone propionate.METHODS Forty-eight male Wistar rats were randomly divided into six groups according to their body weight including normal control group, model group, 40, 80, 160 mg??kg^-1??d^-1 PI group, and finasteride positive control group. In addition to the sham operation for rats in the normal control group, the rats in other five groups performed castration surgery. After the restoration, the five groups of rats were subcutaneously injected with testosterone propionate (10 mg??kg^-1??d^-1) for 10 d to establish a benign prostatic hyperplasia model and then the subcutaneous injection was maintained every 2 d. High, middle and low dose PI groups were intragastrically administered (40, 80, 160 mg??kg^-1??d^-1) from the second day when the benign prostatic hyperplasia model was successfully constructed. The positive control group was given finasteride (1.0 mg??kg^-1??d^-1) .Rats in normal and model groups were given an equal volume of saline for 28 d. After the last administration, the prostate and seminal vesicles were separated under anesthesia in rats, the wet weight and volume of the prostate and seminal vesicles were measured. The prostate and seminal vesicles index were calculated too. Rat blood was drawn and dihydrotestosterone(DHT) and estradiol (E2) in the serum were measured. Nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD) and malondialdehyde (MDA) levels in prostate tissues were measured. The prostate tissue in each group was randomly selected for HE staining. The pathological structure of the prostate tissue was observed under an optical microscope.RESULTS Compared with the normal control group, the prostate gland index and seminal vesicle gland index of the model group increased significantly (P<0.01), and the DHT and E2 levels in serum increased significantly (P<0.01). MDA content was increased while NO levels, NOS and SOD activities were significantly decreased (P<0.01). HE staining showed that the size of the prostate gland in the model group was different, there were obvious dilation, hyperplasia and papillary protrusions, and the cavity was full of pink and homogeneous density. The interstitial tissue showed obvious dilations of blood vessels, infiltration of inflammatory cells, and proliferation of fibrous connective tissues. Compared with the model group, the index and volume of prostate and seminal vesicles in the PI and positive control groups were significantly decreased (P<0.05 or P<0.01), and the levels of serum DHT and E2 in the middle and high doses PI groups were significantly lower (P<0.05 or P<0.01). In all treatment groups, MDA content was decreased and NO, NOS, and SOD levels were increased (P<0.05 or P<0.01) except the low-dose PI groups. There was moderately hyperplasia in low-dose PI group, mild prostatic hyperplasia in positive control group and middle-dose PI group, basically no hyperplasia in high-dose PI group.CONCLUSION PI has a certain inhibitory effect on prostate hyperplasia induced by testosterone propionate, especially in the medium and high dose PI groups. The mechanism may be related to the effects of pueraria isoflavone on antioxidant,free radical scavenging in vivo, increasing NOS activity and increasing NO level.     

����޽�ն����Բ���Ԥ֪�ºʹ̼��յ��Ĵ���������Ϊ���񾭵���ˮƽ��Ӱ��

??OBJECTIVE To investigate the anti-depressant effect of icariin (Ica)in rats with depression caused by chronic unpredictable mild stress (CUMS) as well as the relevant mechanism. METHODS The depression-like rat model with chronic unpredicted mild stress was established. Rats were randomly divided into normal control, CUMS model, CUMS+Fluoxetine (10 mg??kg^-1) and CUMS + Ica(10, 20, 40 mg??kg^-1) groups. Drugs or vehicle were administrated after stress procedures for 21 d. Open-field test (OFT), sucrose preference tests (SPT)and forced swim test (FST) were used to evaluate the anti-depressant effects of Ica. The concentrations of the monoamine neurotransmitters including noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT)in prefrontal cortex, hippocampus, and striatum were measured by HPLC-ECD. RESULTS Behavioral test indicated that crossing score and rearing score in OFT and sucrose preference index in SPT of model group were significantly lower than normal control group(P<0.01), while immobility time in FST was significantly increased (P<0.01). Compared with those in normal control group, the neurotransmitters including NA, DA and 5-HT were significantly decreased (P<0.01) in prefrontal cortex, hippocampus, and striatum in rats of CUMS. Ica and fluoxetine reversed those changes induced by CUMS. CONCLUSION Ica improves the depression-like behaviors of rats induced by CUMS, of which the mechanism might be increasing the contents of monoamine neurotransmitters including NA, DA and 5-HT.     

ľϬ����������ǰ���ٰ�PC3ϸ������������Ƥϸ����ֳ��Ǩ�Ƽ�����ӻ���

??OBJECTIVE To explore the effects of luteolin on the proliferation and migration of the endothelial cells co-cultured with cancer cells and its molecular mechanism. METHODS Human umbilical vein endothelial cells (HUVECs) were primarily isolated and identified by the expression of VE-cadherin. Cancer-endothelial cell co-culture model was established using the Transwell system. The effects of luteolin at different concentrations (0 [Co-culture control], 20 and 50 ??mol??L^-1) on the proliferation and migration of HUVECs in the co-culture system were determined. A HUVECs control group removed of prostate cancer PC3 cells was also included. Human angiogenesis antibody array kit was used to assay the secretion levels of various protein factors in each group. RESULTS VE-cadherin was expressed on all the cultured HUVECs. Increased proliferation ability was found in the HUVECs co-cultured with PC3 cells compared with that in HUVECs control group (P<0.01). Treatment with 20 or 50 ??mol??L^-1 luteolin significantly inhibited the proliferation ability of the HUVECs in co-culture system (both P<0.01). Increased migration ability was found in the HUVECs co-cultured with PC3 cells compared with that in HUVECs control group (P<0.01). Treatment with 20 or 50 ??mol??L^-1 luteolin significantly inhibited the migration ability of the HUVECs in co-culture system (both P<0.01). Secretion levels of multiple angiogenesis-related proteins in the cultural supernatant of co-culture system were significantly increased compared with those in HUVECs control group. Treatment with 20 ??mol??L^-1 luteolin significantly inhibited the secretion levels of interleukin-8 (IL-8), vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1(MCP-1) in the cultural supernatant of co-culture system (all P<0.01). CONCLUSION Luteolin may inhibit the proliferation and migration of endothelial cells via suppressing the secretions of IL-8, VEGF and MCP-1 in cancer-endothelial co-culture system.     

˫���������յ��˸ΰ�ϸ��SMMC-7721����������ӻ����о�

??OBJECTIVE To investigate the apoptosis effect of human hepatocellular carcinoma cell line SMMC-7721 induced by dihydroartemisinin in vitro and the possible mechanism. METHODS After treatment with 25, 50, 100, 200, and 400 ??mol??L^-1 dihydroartemisinin for 24 h. The proliferation inhibitory effect of dihydroartemisinin on SMMC-7721 cell was detected by MTT assay. Cell cycle and apoptosis were detected by flow cytometry. The change of apoptotic morphology was detected by confocal laser scanning microscopy. Rho 123 staining method was used to detect the changes of mitochondrial membrane potential. Western blot was used to detect expression of Bcl-2, Bax, Cleaved Caspase-3, Cleaved Caspase-9 and Cyto C. RESULTS MTT results showed that 25-400 ??mol??L^-1 dihydroartemisinin can inhibit the proliferation of SMMC-7721 cells obviously. The cell cycle detection results of flow cytometry showed that dihydroartemisinin could block SMMC-7721 cell cycle in G₂/M phase. The results of Hochest 333258 staining showed that the nuclei were heterogeneous, condensed and fragmented in the DHA treatment group. The cell apoptosis detection results of flow cytometry showed that the apoptosis rate of dihydroartemisinin treated groups were increased obviously (P<0.01). The results of Rho 123 staining showed that the mitochondrial membrane potential was decreased significantly (P<0.01). Western blot results showed that the expression of Bcl-2 was down-regulated, expression of Bax was up-regulated, the ration of Bax/Bcl-2 was increased and the expression of Cleaved Caspase-3, Cleaved Caspase-9 and Cyto C were up-regulated. CONCLUSION Dihydroartemisinin can induce apoptosis of SMMC-7721 cells, on the mechanism of apoptosis may be related to mitochondrial pathway.     

�Ⱥ�ע��Һ�ٴ���������ϵ����ü������о�

??OBJECTIVE To observe the effect of guhong injection(GHI) on tibial fracture healing in rats and to explore the mechanism of the action of GHI. METHODS One hundred and eighty male SD rats were randomly divided into 6 groups with 30 rats in each group: sham operation group, model group, positive drug group(compound ossotide injection, 5 mL??kg^-1), low, medium and high dose of GHI groups(2.5, 5, 10 mL??kg^-1). In addition to the sham operation group, the other groups established the rat model of tibial fracture. All were given once daily intraperitoneal injections and samples were taken at 1st, 2nd, 4th and 6th week. Blood biochemical analysis and Elisa kit detection were performed on blood samples. X-rays, biomechanical tests, immunohistochemistry and RT-PCR were performed on the tibial samples. RESULTS ??After administration for one, two and four weeks, the levels of serum calcium(Ca) and phosphorus(P) in medium and high dose of GHI groups were higher than those in model group(P<0.05). ??X-ray showed that the outer callus growth and the disappearance of fracture line in all dose groups of GHI were faster than those in model group. ??Compared with model group, the maximum load and rigidity of medium and high dose of GHI groups were increased at each time point(P<0.05), and the trend of stress line graph were improved obviously. ??The content of alkaline phosphatase(ALP) in medium and high dose of GHI groups were higher than that in model group at each time point(P<0.05). Compared with model group, the serum levels of PDGF were increased in all dose groups of GHI(P<0.05 or P<0.01). After administration for one, two and four weeks, the serum BMP-2 in all dose groups of GHI were higher than those in model group(P<0.05 or P<0.01). ??Compared with model group, the expression of Runx2 mRNA were increased in medium and high dose of GHI groups, as well as Smad5 protein expression(P<0.05 or P<0.01). CONCLUSION GHI could significantly improve the biomechanical properties of bone in fracture rats. The promotion of fracture healing might be through the upregulation of PDGF and BMP-2 expression in different stages of bone healing, and the regulation of BMP/Smad5/ Runx2 signaling may be one of the mechanisms of promoting fracture healing.     

巨噬细胞膜仿生白蛋白纳米体系的构建及其胶质瘤靶向递药性能评价

目的 构建包载WEE1激酶抑制剂adavosertib的巨噬细胞膜仿生白蛋白纳米粒(MM-BSA/Ada),体外评估其作为胶质瘤靶向递药体系的可行性。方法 制备MM-BSA/Ada并筛选最佳膜-核比和最佳药-载比,检测其载体安全性和对C6胶质瘤细胞抗增殖活性,考察其体外细胞摄取、跨血脑屏障转运和跨膜后摄取的能力。结果 MM-BSA/Ada具有良好的稳定性,CCK-8结果初步显示,未载药纳米粒在体外细胞实验中对脑血管内皮细胞呈低毒性;与未包膜纳米粒和游离药物相比,MM-BSA/Ada给药后的体外抗胶质瘤细胞增殖活性(P＜0.001)、胶质瘤细胞摄取量(P＜0.001)、体外血脑屏障透过量(P＜0.01)及跨膜后摄取量(P＜0.001)均显著提高。结论 MM-BSA/Ada有较好的胶质瘤靶向递药性能,有望为胶质瘤提供新的放射增敏策略。     

�������ҿ���Ƭ�ڽ��������ڵ�ҩ��ѧ���������ö�

??OBJECTIVE To explore pharmacokinetics and relative bioavailability of penehyclidine hydrochloride in healthy subjects. METHODS This study was an open, randomized and cross-over trial design. Twelve healthy subjects were randomized to receive pharmacokinetic analysis which were performed according to the order of ABC, BCA and CAB, and then pharmacokinetic trial of multiple dose was performed following penehyclidine hydrochloride. Twenty healthy subjects were selected to receive bioavailability study following an order of BD or DB. Blood and urine samples were collected at prescribed time and then investigated by LC-MS/MS. RESULTS The 11 of 12 cases finished the pharmacokinetic trial. The lineare ranges of penehyclidine hydrochloride in plasma and urine were 0.1-8 ng??mL^-1, 1-100 ng??mL^-1, respectively and accuracy of the method was within 85%-115%. The concentration-time curve of penehyclidine hydrochloride was dose dependent within the ranges of 0.4-0.8 mg after oral administration. ??_max and AUC were significantly increased (P<0.01), Vd and CL were significantly decreased (P<0.01) following multiple dose. The relative bioavailability of penehyclidine hydrochloride was (72.44??21.03)%. The average cumulative excretion rate of penehyclidine hydrochloride with original form accounted for (4.98??1.10)% of the total administered dose. CONCLUSION The characteristic of linear pharmacokinetics of penehyclidine hydrochloride is performed in healthy subjects after oral administration. Its excretion is mostly via non-urinary system or other metabolites.