Herald of Medicine

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药物研究

Effect of Dihydroartemisinin on the Proliferation, Migration and Tubelike Structure Formation of Mouse Lymphatic Endothelial Cells

ZHANG Bicheng;ZHAO Yong;WANG Jun;GUO Yan;RAO Zhiguo;GAO Jianfei

2008, 27(08): 879-882.

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ObjectiveTo explore the effect of antimalarial dihydroartemisinin (DHA) on the proliferation, migration and tubelike structure formation of mouse lymphatic endothelial cells (LEC). MethodsBenign lymphangiomas were induced by intraperitoneally injected emulsified incomplete Freund’s adjuvant and mechanically disrupted to obtain LEC. MTT assay was used to observe the inhibitory effect of DHA on the growth of LEC. Apoptosis rate of LEC was evaluated by flow cytometry. Migration and tubelike structure formation of LEC were detected by transwell migration assay and matrigel assay, respectively. The expressions of VEGFR3 mRNA and protein in LEC by DHA were detected by real time quantitative RTPCR and Westernblot, respectively. ResultsDHA at 5－40 μg•mL1 significantly inhibited LEC proliferation and induced apoptosis in a dosedependent manner. Cell migration and tubelike structure formation of LEC were suppressed by DHA. Treated with DHA, the expression of VEGFR3 mRNA and protein of LEC were downregulated. ConclusionDHA can inhibit the proliferation, migration and tubelike structure formation of mouse LEC, induce the apoptosis of LEC,and downregulate the expression of VEGFR3. Our results suggest that DHA might be a candidate as an antilymphangiogenesis inhibitor.

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药物研究

Research of the Relationship between CTGF and Myocardial Fibrosis of SHR and the Drug Intervention

XU Ming;MIN Xinwen;YANG Handong;LI Li;LI Dongfeng

2008, 27(08): 883-886.

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ObjectiveTo evaluate the correlation of CTGF and myocardial fibrosis of SHR and the possibility of CTGF as a new antifibrotic target. Methods32 fourteenweek male SHR were randomly assigned to captopril(100mg•kg-1•d-1)、nifedipine(30 mg•kg-1•d-1)、antisterone(30 mg•kg-1•d-1) and SHR group equivalently, 8 male SD rats with the same age as a control group. Expression of CTGF、 TGF-β1 were evaluated by immunohistochemistry and RT-PCR assay. CVF was measured by MASSON staining, and the concentration of Hypro was detected by alkaline hydrolysis method. ResultsThe LVI、CVF、Hypro and the expression of TGFβ1、CTGF in SHR group were significantly higher than those in SD control group (P＜0.01), which were obviously decreased in the captopril and antisterone groups, compared with those in the SHR group (P＜0.05).ConclusionCTGF is closely connected with myocardial fibrosis of SHR and suppressed by captopril and antisterone. It could be regarded as a new antifibrotic target.

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药物研究

Study of Chitosan on the Transdermal Permeation Enhancing Effect by Metronidazole Gels in vitro

LIU Xinyun;YU Hongmei;HE Xiuli;YE Lihong;XIAO Miaosheng

2008, 27(08): 886-888.

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ObjectiveTo study the effect of chitosan (CS) on cutaneous absorption of metronidazole gel in vitro. Methods1.0% CS was used as penetration enhancer in metronidazole gels, which contained 2% of azone as positive control, and that with no penetration enhancer as the negative control. The rats skin was treated as cutaneous barrier, the cumulative penetrationamount (Q) of Azone group and CS groups, respectively was determined by RPHPLC assay to calculate the stable penetration rate J. ResultsJ of metronidazole gels including 2%Azone and 1.0%CS was 2.841 and 2.874 μg•（cm2）1•h1, respectively, which showed no significant difference (P＞0.05) between each other. However, both displayed significant difference with that in metronidazole gels without any enhancer (P＜0.05). Conclusion1.0%CS could enhance cutaneous absorption of metronidazole, which deserves further research.

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药物研究

Angiotensin II induces Podocytes Apoptosis and the Protective Effect of its Receptor Antagonists

ZOU Minshu;NIE Guoming;YU Jian;HE Weixun;LUO Liman;XU Hongtao

2008, 27(08): 889-892.

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ObjectiveTo investigate the influence of angiotensin II on the apoptosis of glomerular podocytes(PC), and the inhibitor of AT1 and AT2 on podoctyes apoptosis induced by angiotensin II. MethodsPC was cultured with the same concentration of AngⅡ 1×107 mol•L1 for difference time periods or for the fixed time with different concentrations 1×108,1×107,1×106 mol•L1 and detected the percentage of apoptosis and the production of TGFβ1. The podocytes were pretreated with losartan (an inhibitor of AT1) and PD123319(an inhibitor of AT2) for 24 h in other groups, and then exposed to AngⅡ. The percentage of apoptotic PC and the production of TGFβ1 were determined as well. ResultsWith time lasted and concentrations of Ang II increased, PC apoptosis was more obvious and the supernatant levels of TGFβ1 was increased progressively by AngⅡ. Losartan or PD123319 significantly inhibited Ang II induced PC apoptosis and TGF 1 production. The combination of losartan and PD123319 completely blocked the PC apoptosis and recovered TGF 1 production. ConclusionAT1,AT2 receptors are involved in the mediation of AngⅡ induced PC apoptosis by a mechanism involving TGF 1 expression in a time and dosedependent fashion.

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药物研究

Effect of Atorvastatin on the Expression of Integrin α3β1 in the Kidney of Diabetic Rats

ZHANG Huimin;JIA Ruhan;YANG Dingping;LIU Hongyan;DING Guohua

2008, 27(08): 892-895.

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Objective To observe the effect of atorvastatin on the expression of integrin α3β1 in the kidney of diabetic rats. MethodsTwentyone SD rats were randomly divided into three groups: normal rats, diabetic rats, diabetic rats treated with atorvastatin (20 mg•kg1•d1) for 8 weeks. Blood glucose,blood lipid, serum creatinine, urinary albumin excretion and Ccr were measured after 8 week’s treatment; the expression of integrin α3β1 was determined by immunochemistry; the level of lipid peroxidatin(MDA) and total antioxidative capacity(TAOC) were examined by colorimetric method; the renal tissue pathology was observed under light microscope; In addition, the ultrastructure of glomeruli was observed by electron microscope. ResultsNo significant differences of blood glucose and blood lipid were found between the diabetic rats and the atorvastatin treated rats; Compared with those of the diabetic rats, the level of Ccr, urinary albuminin excretion and the renal MDA of the treatment rats were decreased significantly, but the activities of renal TAOC and the expression of integrin α3β1 were increased markedly; renal pathologic changes were also improved ConclusionAtorvastatin attenuates proteinuria, improves renal pathology and protects renal function in the early stage of diabetes though decreasing the level of reactive oxygen species and upregulating the expression of the integrin α3β1.

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药物研究

Antiaging Effect of αLipoic Acid on Dgalactose Induced Aging Mice

KANG Hua;KUANG Rong

2008, 27(08): 896-898.

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ObjectiveTo investigate the antiaging effect of αlipoic acid on aging mice induced by Dgalactose. Methods60 mice were divided into 6 groups randomly: normal group, the model group, Vit E group (100 mg•kg1), different doses of αlipoic acid (200, 100 and 50 mg•kg1). The aging model was established by s.c.injecting Dgalactose daily, for consecutive 40 d. Mice were i.g. three doses of αlipoic acid, and controls for 40 d. The levels of SOD in RBC, SOD、GSHPx、MDA、NO in blood serum and Na＋K＋ATPase、MAO in brain tissue were detected. ResultsCompared with model group , αlipoic acid obviously improved SOD in RBC; content of GSHPx,,decreased MDA and NO in blood serum, and significantly stimulated Na＋K＋ATPase, suppressed MAO in brain tissue.ConclusionαLipoic acid shows a good antiaging action on the aging murine model induced by Dgalactose.

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药物研究

Antioxidative Effects of Total Coumarins from Peucedanum Praeruptorum Dunn in vitro

WANG Decai;ZHANG Xianzhong;FENG Lei

2008, 27(08): 899-901.

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ObjectiveTo investigate the eliminating effect on oxygen radicals by total coumarins from Peucedanum Praeruptorum Dunn(TCP) and its inhibitory effect on lipid peroxidation. MethodsHydroxyl free radical (•OH) was produced by Fenton reaction and superoxide anion free radical(O-2•) was produced by the oxidation of pyrogallol. The inhibition on lipid peroxidation as the content of MDA was determined by colorimetry. ResultsTCP strongly eliminated oxygen radicals with the EC50 being 287.1 and 124.8 μg•mL1 for•OH and O-2•, respectively. EC50 for MDA suppression by TCP was 409.5 μg•mL1. ConclusionTCP could eliminate oxygen radicals and inhibit lipid peroxidation in a dose related manner.

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药物研究

Effects of Irbesatan on the Connective Tissue Growth Factor of Rats with Diabetic Nephropathy

SONG Enfeng;LIU Meng;JIA Ruhan;XIANG Qiong

2008, 27(08): 902-904.

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ObjectiveTo investigate effects of irbesatan(angiotensin Ⅱ receptor antagonist,IRB) on the connective tissue factor (CTGF) in type 2 diabetic rats.MethodsThe model of diabetic nephropathy (DN) was established by right kidney removed+high fat diet+STZ injection on SD rats. The rats were randomly divided into 3 groups:a diabetic nephropathy model group,IRB treated group and a group with sham operation. The blood glucose, insulin, lipid,urine protein for 24 h and Ccr were measured. Immunohistochemistry was applied to measure the expression of CTGF in the nephridial tissue. ResultsThe blood glucose,insulin,lipid,urine protein for 24 h, Ccr and the expression of CTGF in the sham operation group was lower than those in the DN group（P＜0.05）. CTGF in kidneys showed positively related with urine protein and the glomerular volume（P＜0.05）. ConclusionThe expression of CTGF was increased in group DN.IRB may protect kidney by suppressing the expression of CTGF.

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药物研究

Low Dose Arginine Vasopressin Increase Spatial Learning and Memory Ability in Rats

QU Min;JIANG Zhengyao;HE Xuebin

2008, 27(08): 905-907.

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Objective To study the effect of multiple low dose of arginine vasopressin (AVP) on the spatial learning and memory ability in rats. MethodsWistar male rats were treated with different doses of AVP (0.5 and 1.0 μg•kg1) or saline (0.12 mL) by subcutaneous injection 30 min before training, then the ability of their spatial learning and memory and doseeffect relationship were measured by Morris water maze method. ResultsNo evident difference of the latent period and distance in the hidden platform test was observed between rats administrated with 0.5 and 1.0 μg•kg1AVP. In the probe test, however, the swimming durance and distance in the quadrant for rats treated with AVP (0.5 and 1.0 μg•kg1) were significantly longer than those in control group, moreover, no significant difference between three groups of rats on the motive to find the platform and visual acuity. ConclusionMultiple low dose of periphery AVP could increase long term memory of the rats.

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药物研究

Study of the Cellular Mechanism Underlying the Venous Injury by Sodium Aescinate

ZHU Huifen;XU Rong;XIE Ying;ZENG Fandian

2008, 27(08): 908-911.

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Objective To observe the effect of sodium aescinate(EscNa) on the activity of human umbilical vein endothelial cell(HUVEC) and the cell cycle. MethodsCultured HUVEC were treated with EscNa or tumor necrosis fatorα (TNFα) at different concentrations for 24 hours. MTT method and the neutral red method were employed to detect the cellular activity. The cell cycle of HUVECs was measured by flow cytometry. ResultsThe results showed that the halfmaximal inhibiory concentrations（IC50）of EscNa were(42.89±3.42) for MTT and( 44.19±3.58) μg•mL1for neutral red methool . At the concentration between 10 to 80 μg•mL1,EscNa inhibited the growth of HUVEC in a concentration dependent manner. It was also showed that EscNa decreased the Sphase cells and reduced G2•M phase cells to inhibit the proliferation of HUVEC. ConclusionEscNa exerted the cytotoxic effects to HUVEC by decreasing the cellular activity and inhibiting the cellular proliferation.

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药物研究

Adenosine Promotes Proliferation of Neural Stem Cells in vitro

CHEN Xiaping;DU Shiming;WANG Qibin;ZHANG Che;ZHANG Penghua;ZHU Xiaohu

2008, 27(08): 911-914.

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ObjectiveTo study the effects of adenosine on proliferation of neural stem cells in vitro. MethodsPrimary neural stem cells(NSCs) from newborn mice were cultured, neurospheres were observed, and immunocytochemical staining of characteristic protein and BrdU labeling were performed to identify NSCs and their proliferative properties. Adenosines with 0.4, 2.0, 10.0 μmol•L1 were respectively added to the cultured NSCs, and at the same time, a vehicle control and positive control were set up. The morphology of NSCs was observed with the convert phase microscope, the neurosphere numbers were counted, and NSCs viability was determined with MTT assay in order to analyze the proliferation of NSCs by adenosine in vitro. ResultsA great deal of neurospheres were formed in cultured cells, the characteristic protein of NSCs and BrdU labeling were positive, which suggesting that the cultured cells were NSCs, and had the potential of selfrenewal and selfproliferation.The number of neurosphere and the A values of 2.0 μmol•L1 and 10.0 μmol•L1 adenosine treated group, respectively were significantly higher than those of the vehicle control group. ConclusionAdenosine shows effects of promoting the proliferation of neural stem cells.

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药物研究

Study on the Relative Bioavailability of Diammonium Glycyrrhizinate Capsule in Healthy Volunteers by HPLCMS

JIN You;YANG Jun;WEI Lei;WU Pengfei;LONG Lihong;CHEN Jianguo;

2008, 27(08): 915-917.

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ObjectiveTo develop a LCMS assay for determination of glycyrrhetic acid in human plasma and to estimate the relative bioavailability of diammonium glycyrrhizinate capsules in 20 healthy volunteers. MethodsAccording to a randomized twoperiod crossover design, 20 healthy volunteers were orally administered with 150 mg diammonium glycyrrhizinate capsules or reference ones, respectively. Glycyrrhetic acid in plasma was determined by LCMS with ursolic acid used as internal standard,　and the data were processed with DAS 2.0 pharmacokinetic program. ResultsThe pharmacokinetic parameters of the two tablets were as follows: AUC0t were (1 648.49±230.55) and （1 609.27 ± 265.59） ng•mL1•h, Cmax were （95.97±14.99） and （93.05±17.91） ng•mL1, tmax were (12.00±1.30) and (11.80±1.44) h, respectively. ConclusionThe concentrationtime curves of two tablets are consistent with a twocompartment model. The mean relative bioavailability is (103.5±12.7)%（AUC0t）,both of which are bioequivalent.

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药物研究

Influence of Jinkuishenqiwan on Mice Myelosuppression Induced by Cyclophosphamide

WU Haitao;GU Hai;YIN Xing;LIU Yuanjun;JIANG Lihua;WANG Mingyan

2008, 27(08): 923-924.

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ObjectiveTo study the influence of jinkuishenqiwan on myelosuppression in mice induced by cyclophosphamide. Methods 30 mice were randomly divided into 3 groups: the model control, the jinkuishenqiwan group and the blank control, which were administrated by gavage with jinkuishenqiwan 0.125 mL•d1 , the same volume of distilled water for 10 days, respectively. The model was established by injecting cyclophosphamide for 3 consecutive days at 40 mg•kg1 daily. Thereafter, the bone marrow hematoplast and bone marrow cell micronucleus were observed and analyzed. ResultsJinkuishenqiwan significantly inhibited the decrease of mouse bone marrow hematoplast and the increase of bone marrow cell micronucleus ratio caused by cyclophosphamide（P＜0.01）. Conclusion Jinkuishenqiwan could relieve the mice myelosuppression induced by cyclophosphamide.

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药物研究

Effects of Oxymatrine on Human Prostate Cancer PC-3 Cells in vitro

ZHANG Xiantu;ZHANG Zhong;WANG Xianyou;HAN Zihua

2008, 27(08): 925-927.

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ObjectiveTo study inhibition and mechanisms of oxymatrine(OMT)on the growth of human prostate cancer PC3 cells in vitro. Methods Cell suppression rates were measured by MTT assay, cell cycle were measured by flow cytometry and expressions of bcl2 and bax protein inside PC3 were detected by immunohistochemistry. ResultsInhibition on the growth of prostate cancer cell was intensed by OMT in a dose and time dependent manner in vitro(P＜0.05). The ratio of G0/G1 and S phase cells was increased and the ratio of G2/M phase cells was decreased, with the addition of OMT. Meanwhile, expression of Bcl2 protein was downregulated and Bax protein was upregulated. ConclusionOMT could inhibit the growth of human prostate cancer PC3 cells by directing cell cycle arrested at G0/G1 and S phase,downregulating Bcl2 protein expression and upregulating Bax protein expression

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药物研究

Study on the Acute Toxicity and Main Therapeutic Effects of Qianliean Granules

GUO Jin;LIU Linggai;HU Yulu;RONG Chengcai;ZHOU Chunhua

2008, 27(08): 928-930.

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ObjectiveTo verify the curative effects of qianliean granules for providing the basis for its clinical use. MethodsAcute toxicity and the main pharmacodynamics experiments were carried out. for exploring the influence of qianliean granules on nonbacterium prostatitis induced by 1.5% carrageenin on rats, ears swelling by dimethylbenzene and the change of abdominal capillary permeability causd by 0.6% acetic acid. ResultsLD50 wasn’t able to be detected the largest tolerated dosage was 96 g•kg1•d1, which was equal to 224.3 times of that for adults. Qianliean granules suppressed the inflammation caused by carrageenin, by increasing the density of lecithin inside prostate tissue, and the formation of granuloma. It also obviously inhibited the inflammation induced by dimethylbenzene. Qianliean granules significantly reversed the increase of capillary permeability by 0.6% acetic acid. ConclusionQianliean granules is safe for clinical application on inhibiting prostatitis.

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药物研究

Effects of Oxymatrine on Human Bladder Cancer T24 Cell Line

CHEN Zhenqian;CHEN Qi

2008, 27(08): 931-933.

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ObjectiveTo study antitumor effects and mechanism of oxymatrine(OMT) on human bladder cancer T24 cell line in vitro. MethodsCell suppression rates were detected by MTT assay, cell cycle was measured by flow cytometry and expressions of bcl2 and bax protein were detected by immunohistochemistry. ResultsCell suppression rates were 14.10% and 49.67%, after treated with 2 mg•mL1 OMT for 24 and 72 h, respectively. The rates increased to 35.40% and 80.50% by 8 mg•mL1 OMT. The ratio of G0/G1 phase cells was increased and the ratio of G2/M phase cells was decreased. Bcl2 protein expression was downregulated and Bax protein expression was upregulated after different treatment of OMT. ConclusionOMT could inhibit the growth of human bladder cancer T24 cell by inducing cell cycle arrest at G0/G1 phase, which may be related to the downregulation of Bcl2 protein expression and upregulation of Bax protein expression.

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药物与临床

Effects of Colon Dialysis with the Traditional Chinese Medicine on Endotoxin、TNFα、IL6 and IL2 in Patients with Severe Chronic Hepatitis

SHI Weizhen;WANG Yufang;GUO Jianchun;SHI Junping;LIU Yan;CHEN Qunwei;XUN Yunhao

2008, 27(08): 935-937.

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ObjectiveTo investigate effects of colon dialysis with the traditional Chinese medicine on endotoxin, tumor necrosis factorα, interleukin6 and interleukin2 in patients with severe chronic hepatitis. Methods60 patients with severe chronic hepatitis were randomly divided into the treatment group and control group. The controls were received conventional treatment of hepatoprotection, and the treatments were given conventional treatment and colon dialysis with the traditional Chinese medicine. The symptoms and physical signs of patients were observed, the liver function and changes of blood endotoxin and cytokines (tumor necrosis factorα,interleukin6, interleukin2) were measured before and after 4 weeks of treatment. ResultsThe liver function and prothrombin time were significantly improved in the treatment group than those in the control group（P＜0.01）. The levels of endotoxin, tumor necrosis factorα and interleukin6 were significantly lowered in the treatment group（P＜0.01）. No significant difference of IL2 was found between two groups. ConclusionThe colon dialysis with the traditional Chinese medicine could improve the liver function of patients with chronic severe hepatitis. It removes endotoxin, tumor necrosis factorα and interleukin6, but doesn’t change the level of interleukin2.

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药物制剂

Preparation and Drug Release Characteristics of the pH-sensitive Dextran Hydrogel Nanoparticles

ZHANG Hui;WU Hong;FAN Li;LI Fei

2008, 27(08): 967-970.

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ObjectiveTo prepare the pH-sensitive glycidyl methacrylate derivatized dextran (dexGMA)/acrylic acid (AAc) poly(dexGMA/AAc) nanoparticles, and study their properties such as drug release and degradation. MethodsThe poly(dexGMA/AAc) nanoparticles were prepared by emulsion polymerization. Under different pH, the particle size distribution and drug release of poly(dexGMA/AAc) nanoparticles were determined by dynamic dialysis methods with erythromycin as a drug model. Results The mean diameter of poly(dexGMA/AAc) nanoparticles was about 100 nm, the drug loading rate and encapsulation efficiency were 90.7%, and 1.06%,respectively.In the artificial gastric fluid without enzymes(SGF), the cumulative drug release ratio was 7.0% within 2 h, afterwards reached to 37.0% within 4 h in the artificial intestinal fluid (SIF) without enzymes. ConclusionThe poly(dexGMA/AAc) nanoparticles were pHsensitive, which released EM slightly in SGF, whereas released considerably more in SIF by swelling and degradating. It is suggested that the poly(dexGMA/AAc) nanoparticle would be a potential colontarget carrier.

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药物制剂

Spraying Granulation Technique for Guyanning Granules

LV Yi;LIU Yani;CHEN Huating

2008, 27(08): 970-972.

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ObjectiveTo select the optimum condition for the spray granulation of guyanning granules. MethodsThe newlyfluidbedspraydriergranulation technique was adopted with the temperature of exit and entry（A）,blast pressure（B）and condensed solution（C） as inspecting factors, three levels of each factors, the content of caffeotannic acid in semifinished guyanning granules as inspecting markers by the orthogonal experiment. ResultsThe temperature of exit and entry was most notable（P＜0.01) among three factors. However, blast pressure and extracting technique was of little importance. ConclusionThe optimum spraying granulation technique of guyanning granules is A1B3C3, which is that A: 90－100/50－60 ℃, B:－1 800 Pa

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