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1.
??OBJECTIVE To investigate the cardioprotective effect of exogenous zinc (Zn2+)on the mitochondrial pathway, and to explore its possible mechanism. METHODS Rat heart tissue-derived H9c2 cardiac cells were cultured, and then randomly divided into control group, ZnCl2 group (1-20 ??mol??L-1, 20 min), ZnCl2 plus inhibitor group [PI3K inhibitor LY294002, 10 ??mol??L-1 and mitochondrial ATP sensitive potassium channel (mKATP) inhibitor 5-HD, 0.5 mmol??L-1, inhibitors treated cells for 10 min and then ZnCl2 20 min] and inhibitor group (10 min). The mitochondrial permeability transition pore (mPTP) opening was evaluated by measuring mitochondrial membrane potential (????m). Tetramethylrhodamine ethyl ester (TMRE) diacetate fluorescence images were obtained with laser scanning confocal microscopy. GSK-3?? and AKT phosphorylation were determined with Western blot. The cells were subjected to simulated ischemia/reperfusion injury, cell viability were determined with flow cytometry. Cells were transfected with constitutively active GSK-3??-S9A(GSK-3??-S9A)plasmid by Fugene 6 transfection kit, mPTP opening was evaluated by confocal microscopy. RESULTS Compared with the normal, exposure of cells to H2O2 for 20 min caused a marked decrease in TMRE fluorescence, treatment of cells with different dose of Zn2+ prevented the loss of TMRE fluorescence caused by H2O2 with the peak at 10 ??mol??L-1. Western blot showed that Zn2+significantly enhanced the GSK-3?? and AKT phosphorylation, the effect that was significantly reversed by LY294002, but not 5-HD. Compared with the normal, ischemia/reperfusion markedly reduced cell viability. Zn2+ applied at ischemia did not increase the cell viability, but significantly increased the cell viability when given at reperfusion. Zn2+could mimic the specific mPTP inhibitor cyclosporin A (1 ??mol??L-1) and prevent the mPTP opening, which was again reversed by LY294002 but not 5-HD. Zn2+ was not able to exert protection in cells transfected with the GSK-3??-S9A. CONCLUSION Zn2+ can induce myocardial mitochondrial protective effect by modulating the mPTP opening through the inactivation of GSK-3?? via PI3K/AKT pathway. mKATP may not be involved in the action of Zn2+.  相似文献   

2.
??OBJECTIVE To investigate the effects of lithium chloride (LiCl) on neuroapoptosis in hippocampus induced by isoflurane and the relationships with GSK-3??/CRMP2 pathway in neonatal rats. METHODS Sixty neonatal rats at postnatal day 7 were assigned randomly into air+NS group, air+LiCl group, Iso+NS group, Iso+LiCl2, Iso+LiCl4 and Iso+LiCl8 group .Rats in groups of air+NS and air+LiCl were exposed to air for 6 h. Rats in groups of Iso+NS, Iso+LiCl2,Iso+LiCl4 and Iso+LiCl8 were exposed to 0.75% isoflurane for 6 h. Rats in groups of Air+NS and Iso+NS were injectedintracerebroventricularlywith NS 5 ??L separately 30 min before exposure to air or isoflurane. Rats in groups of air+LiCl, Iso+LiCl2, Iso+LiCl4 and Iso+LiCl8 were injected intracerebroventricularly with LiCl 5 ??L separately 30 min before exposureto air or isoflurane. Rats in groups of Iso+LiCl2, Iso+LiCl4,Iso+LiCl8 and Air+LiCl were injected intracerebroventricularly with LiCl 5 ??L separately 30 min before exposure with the different concentrations(20,40, 80,80 mmol??L-1,respectively). At the end of exposure, the hippocampus of some rats were separated and proteins expression of cleaved caspase-3, phospho-GSK-3??(p-GSK-3??), GSK-3??, phospho-CRMP2(p-CRMP2) and CRMP2 were detected by Western blot (n=5); other rats were perfused and their brain were embedded by paraffin 2 h after exposure, the neuroapoptosis in the hippocampus CA1 area was detected by TUNEL staining (n=5). RESULTS Lithium chloride (80 mmol??L-1) significantly decreased the cleaved caspase-3 levels(P<0.01)induced by isoflurane in hippocampus of neonatal rats. TUNEL positive cells in CA1 area were significantly decreased by 41.69%(P<0.01)in group Iso+LiCl8 when compared with those in group Iso+NS.The protein expressionof p-GSK-3?? and p-CRMP2 in group Iso+NS were significantly decreased and increased respectivelycompared to those in group air+NS. The ratio of p-GSK-3??/ GSK-3?? and p-CRMP2/CRMP2 in the hippocampal increased 41.03%(P<0.05) and decreased 23.64%(P<0.05)respectively in Iso+LiCl8 group when compared with Iso+NS group.CONCLUSION Lithium chloride attenuates isoflurane-induced neurodegeneration through inhibiting hippocampal neuroapoptosis in neonatal rats. Inhibition of the activation of GSK-3??/CRMP2 signaling pathways may involve in the mechanisms.  相似文献   

3.
??Secretory phospholipase A2 group ??A is an enzyme that hydrolyzes the sn-2 ester in glyceroacyl phospholipids present in lipoproteins and cell membranes. There have been an increasing number of reports regarding the pathogenesis of the enzyme in cardiovascular,tumor and autoimmune diseases in recent years and drug development targeting the enzyme is receiving more and more attention as a result. This article reviews research RESULTS in the above areas and current status of drug development based on reported sPLA2-II inhibitors.  相似文献   

4.
??OBJECTIVE To study the pharmacokinetics and bioequivalence of hydroxysafflor yellow A (HSYA) and hydroxysafflor yellow A nanoemulsion (HYAN) in rats.METHODS Twelve male rats were randomly divided into two groups. The rats were administered intragastrically with HSYA or HYAN, respectively, and then blood was collected from the venous plexus at different time points. HPLC method was used for the determination of HSYA blood concentration.RESULTS The main pharmacokinetic parameters of HYAN were as follows: the area under curve (AUC0-24 h), peak concentration (??max), peak time (tmax) and clearance (CL) were (31.56??4.58) mg??L??h-1, (12.75??2.64) mg??L-1, (0.83??0.54) h and (1.89??0.93) L??h-1??kg-1, respectively. The AUC0-24 h, ??max and tmax of HYAN increased by 5.49, 10.22 and 2.50 times, respectively, and the CL of HYAN was only 1/4 of that of HSYA. The 90% confidence intervals for AUC0-24 h and ??max were not within the prescribed range of bioequivalence criteria.CONCLUSION Relative to HSYA, the high plasma concentration and prolonged peak time of HYAN in vivo can significantly improve the oral bioavailability of HSYA. HSYA solution and HYAN are not bioequivalent.  相似文献   

5.
??OBJECTIVE To study the intellectual property provisions relating to drug regulation in the TPP agreement, analysize the interaction mechanism between drug regulation and intellectual property rights on the basis of information sharing, study the possible impact, and then discusses the references to China. METHODS This article analysizes the TPP final text and relevant research literatures, study the interaction mechanism between drug regulation and intellectual property rights and the possible impact of,and then discuss the relevantlaw of China. RESULTS The TPP agreement provides several intellectual property provisions relating to drug regulation, demanding the concordant relation between the registration of pharmaceutical and patent protection period, drug data protection and patent protection,which will establish the interaction mechanism based on information sharing. The intellectual property provisions relating to drug regulation are a summary of the experience of the TPP parties forming a coordinated and interactive mechanism between encouraging innovation and ensuring drug safety and an attempt to a wide range practice, which will have abroad impact on the bio-pharmaceutical industry. CONCLUSION Refer to the relevant experience in TPP agreement, China can amend the Pharmaceutical Administration Law and the Patent Law in the process of revision by improving the information sharing mechanism to achieve a higher level of institutional interaction.  相似文献   

6.
??OBJECTIVE To isolate and purify 2??,3??,24-trihydroxy-12-alkene-28-ursolic acid from the roots of Actinidia eriantha Benth, establish its determination method, and compare the contents in different extracted parts and samples from different sources. METHODS An HPLC-PDA method was established for the content determination. The contents of 2??,3??,24-trihydroxy-12-alkene-28-ursolic acid in the roots of Actinidia eriantha Benth from five different sources and different extracted parts were determined by standard curve method. RESULTS The content of 2??,3??,24-trihydroxy-12-alkene-28-ursolic acid was higher in the samples from Shouning county of Fuzhou city and Yunhe county of Lishui city while lower in those from Yongjia county of Wenzhou city and Lishui city. And in different extracted parts, the content was the highest in dichloromethane part, lower in ethanol part, and the lowest in methanol part. CONCLUSION The method is stable and accurate with good reproducibility and can be used for the determination of 2??,3??,24-trihydroxy-12-alkene-28-ursolic acid in the roots of Actinidia eriantha Benth. The content of 2??,3??,24-trihydroxy-12-alkene-28-ursolic acid is different in Actinidia eriantha Benth samples from different sources, which is the highest in dichloromethane part.  相似文献   

7.
??OBJECTIVE To study the chemical constituents of Microtropis triflora Merr. et Freem. METHODS The compounds were isolated and purified by various chromatographic technigues such as silica gel, Sephadex LH-20, and pre-HPLC. Their structures were identified on the basis of chemical properties and spectral analysis. RESULTS Ten triterpenes were isolated and elucidated as 3, 25-epoxy-1??, 3??, 11??, 12, 23, 25-hexahydroxy-urs-12-en(1), ??-amyrin(2), ??-amyrin palmitate(3), 3??-hydroxy-11-oxo-olean-12-enyl-3-palmitate(4), lupeol(5), friedelin(6), 3-oxo-28-friedelanoic acid(7), oleanolic acid(8), salaspermic acid(9), and orthosphenic acid(10). CONCLUSION Compound 1 is a new compound and has cytotoxic activity against Bcap37 and SMMC7721 cells with IC50 values of 27.86 and 11.38 ??g??mL-1, respectively.  相似文献   

8.
??OBJECTIVE To evaluate the compatibility of 3-layer coextrusion (powder-liquid) infusion bag with lactose azithromycin powder and sodium chloride injection. METHODS The sterile powder of lactose azithromycin was dispensed in different infusion bags and the turbidities were observed after the accelerated test. The dissolve degree of packaging materials and additives, including infusion membrane and inner cap, in different acid, alkali and polar solvent were studied. The extent of migration of packaging material components into the drugs were researched after the lactose azithromycin powder and sodium chloride injection were dispensed in the 3-layer coextrusion (powder-liquid) infusion bag. RESULTS Compared with the four kinds of common membrane, the membrane material we chosed was the best and the turbidities of liquid were meet the specification. In the extraction studies of different test solution, the antioxidant was not checked out, and the content of both Mg and Al was less than 0.05 ??g??mL-1. In the security evaluation of migration, the maximum migration, the biggest one-day intake value and the accumulated maximum intake of additives in the special infusion bag were far lower than its toxicology statistics. CONCLUSION The quality of 3-layer coextrusion (powder-liquid) infusion bag is good. The migration and adsorption degree of of packaging material are tested to make sure the packaging material could ensure the drug quality and stability. The compatibility of 3-layer coextrusion (powder-liquid) infusion bag with drug is nice.  相似文献   

9.
??OBJECTIVE To investigate the chemical constituents in the roots of Allium tuberosum. METHODS Colum chromatography with different materials such as silica gel was used to isolate and purify the chemical constituents. Their structures were identified by spectroscopic analysis. RESULTS Nine compounds were isolated from the roots of Allium tuberosum and their structures were identified as 4,8-dihydroxyacetophenone-8-O-ferulate(1), 4,8-dihydroxyacetophenone(2), 3,4,5-trimethoxybenzoic acid(3), 3,4,5-trimethoxycinnamic acid(4), buddlenol D(5), E-1,6,11-triene-4,5,9-trithiadodeca-9,9-dioxide(6), tianshic acid(7), daucosterol(8), and linoleic acid(9). CONCLUSION Compound 1 is a new compound and compounds 2-5 are obtained from Allium tuberosum for the first time.  相似文献   

10.
??OBJECTIVE To establish a method for simultaneous determination of 56 kinds of pesticide residues in Radix Ophiopogonis by using gas chromatography tandem mass spectrometry (GC-MS/MS), and apply it to screening of 137 batches of samples. METHODS The forbidden, restricted and frequently-used pesticides were selected as the detecting indexes. The samples were prepared by QuEChERS, and quantitative analysis was carried out by GC-MS/MS in multiple-reaction monitoring (MRM)mode. There were three supplemental levels for detection recoveries and RSD. RESULTS All the 56 pesticides had good linearity in certain ranges with correlation coefficients(r) higher than 0.997 8. The recoveries of 96.4% pesticides ranged from 60% to 130% at three supplemental levels (1, 2 and 10 LODs), with the RSDs of 92.9% pesticides less than 15%. The LODs for most of the selected pesticides were below 0.01 mg??kg-1. Twelve pesticides were detected in 137 batches of samples. CONCLUSION The detecting indexes are meaningful and the developed method is simple, rapid, sensitive and reliable for screening multiple pesticide residues in Radix Ophiopogonis. The test result has certain reference value for the cultivation and distribution supervision of Radix Ophiopogonis.  相似文献   

11.
??OBJECTIVE To study the antitumor effect of Pileostegia tomentella 95% alcohol extract (PTAE) on H22 tumor-bearing mice and its possible mechanisms. METHODS Sixty mice were chosen and mouse models bearing H22 solid tumor were established in fifty mice, and the others were as normal control. H22 tumor-bearing mice were randomly divided into five groups:model control group, fluorouracil group(20 mg??kg-1), PTAE high, middle and low-dose group(180, 90, 45 g??kg-1 of crude drug, respectively). The mice in treatment groups were intragastric administration respectively, meanwhile, the mice in normal control and model groups were treated with the same volume of distilled water, once a day for ten days. The blood was collected from eyeball in all mice, and the serum were separated and detected by ELISA for IL-2 and TNF-??.Then the mice were put to death. Their tumors, thymuses and spleens were separated and weighted, and the tumor inhibitory rates, thymus and spleen indexes were calculated. The pathological change of tumor tissue was observed. RESULTS Compared with model control group, the tumor weights of PTAE high and middle-dose groups were significantly decreased (P??0.05, P??0.01), the tumor inhibitory rates were 37.44% and 38.46% respectively. The spleen index of PTAE middle-dose group was increased significantly (P??0.01). The level of IL-2 in serum of tumor-bearing mice in the PTAE high-dose group was increased significantly(P??0.05), and the level of TNF-?? in serum (P??0.01) could be increased significantly in the PATE high, middle and low-dose groups. CONCLUSION Pileostegia tomentella 95% alcohol extract has antitumor activity, its mechanism may be developed by immuno-regulation.  相似文献   

12.
13.
??OBJECTIVE To analyze the cost-effectiveness of irbesartan and bisoprolol using Markov model for the purpose of choosing a secure and effective therapy for hypertension with heart failure. METHODS Markov state transition model was built to simulate the dynamic changes of the four states (event free, non-fatal myocardial infarction, non-fatal stoke and death) in the hypertension with heart failure patients who received the irbesartan or bisoprolol treatment. Markov model was applied using roll back analysis, Markov cohort simulation to project the costs and effectiveness for the hypertension with heart failure who had been long-term treated with irbesartan or bisoprolol. One way sensitivity analysis was carried out to determine the robustness of this baseline results. RESULTS The results of cost-effectiveness analysis showed that patients receiving irbesartan cumulative costs and effects were 60 635.48 yuan and 6.22 quality-adjusted life years gained. Patients receiving bisoprolol cumulative costs and effects were 58 185.12 yuan and 6.17 quality-adjusted life years gained and the ICER was 49 007.20 yuan/QALYs. According to the sensitivity analysis, the change of key parameters in the set range did not affect the model results. CONCLUSION Bisoprolol treatment is more economical than irbesartan treatment for hypertension with heart failure patients. This study could be used as methodology reference of pharmacoeconomics on the hypertension with heart failure diseases for Chinese pharmacoeconomist.  相似文献   

14.
??OBJECTIVE To advocate Patient Assistant Program Projects (PAP Projects) decision-making, this study assesses the long-term cost-effectiveness of 1-year adjuvant trastuzumab therapy for women with human epidermal growth factor receptor 2 (HER2) positive early breast cancer. METHODS A Markov model tracked yearly patients?? transitions between five health states. The cycle length was 1 year and the sum was 45. From the perspective of the China health insurance system, the direct medical cost was estimated based on a survey of clinical expert panels. A discounting rate of 3% was used to discount direct medical cost and health outcomes. Utility and transition probabilities were retrieved from the HERA trial and literature. To estimate the direct medical cost, a survey of clinical expert panels was conducted. The cost of trastuzumab and HER2 test based on Roche. The key factor of the model was realized by one-way sensitivity analysis. The result of a probability sensitivity analysis conducted by Monte Carlo simulation was expressed as an incremental cost-effectiveness scatter plot. RESULTS Without PAP Projects in Guangzhou, the adjuvant trastuzumab treatment prolonged 1.79 QALYs when the cost increased ??53 301 and the Incremental cost-effectiveness ratio (CER) was ??29 731/ QALY, which is cost-effective based on Guangzhou's per capita GDP in 2015. With PAP Projects, the adjuvant trastuzumab treatment was totally cost-effectiveness. The sensitivity analysis demonstrated that the model was moderate. CONCLUSION One year adjuvant trastuzumab treatment is a cost-effective therapy for patients with HER-2 positive breast cancer. With PAP Projects in Guangzhou, the adjuvant trastuzumab treatment is projected to be associated with improved QALYs and reduces direct medical costs, compared with the standard chemotherapy, represents a dominant treatment option among patients with HER2-Positive Early Breast Cancer. PAP Projects in Guangzhou should be persisted and spread in China.  相似文献   

15.
??OBJECTIVE To prepare capsaicin-solid lipid nanoparticles (CAP-SLNs) and study their physical and chemical properties. Then, the CAP-SLNs were modified with chitosan (CTS) and the pharmacokinetics across colon of rats was studied in vivo. METHODS CAP-SLNs were prepared by emulsion-solvent evaporation method. The mean size, encapsulation efficiency and drug loading of the nanoparticles were investigated. RESULTS The average diameter of CAP-SLNs was (118.89??25.0) nm, the encapsulation efficiency was (38.56??2.6)%, and the drug-loading was (6.17??0.21)%. After colon-specific delivery in rats, the AUC0-360 min(243.63??61.46) mg??min??L-1 and ??max(1.23??0.18) mg??L-1 of CTS-CAP-SLNs were 1.81-fold and 1.95-fold higher than CAP. CONCLUSION It is simple and feasible to prepare CAP-SLNs by emulsion-solvent evaporation method. The pharmacokinetic parameters in rats are improved remarkably compared with CAP.  相似文献   

16.
??OBJECTIVE To synthesize a novel cationic cholesterol derivative, N-(N??,N??-dimethyl)propyl succinic mono-cholesteryl mono-amide(DMAPA-CHEMS), and evaluate its feasibility as a none-viral gene vehicle. METHODS DMAPA-CHEMS and phospholipid were employed to produce liposomes by thin membrane dispersion method, and the morphology of liposomes was observed under transmission electron microscope. The average diameter and Zeta potential were determined by laser particle size analyzer. The combination to and protection for DNA were investigated via agarose gel electrophoresis. The uptake of FITC-labelled oligonucleotides into HepG2 cells was determined by flow cytometry, while the transfection promotion of liposomes for GFP-plasmid DNA was observed by inverted fluorescence microscope. RESULTS The obtained liposomes showed regular shape and uniform size, with a mean diameter of 94.0 nm and Zeta potential of 24 mV. The liposomes could combine DNA completely and protect DNA from the degradation of DNase I when the charge ratio of cationic cholesterol to DNA was more than 4. The cationic liposomes had low cytotoxicity. Although the uptake efficiency of liposomes made of DMAPA-CHEMS was lower than that of DC-Chol, the gene expression efficiency was higher. CONCLUSION DMAPA-CHEMS is a novel gene carrier with high transfection efficiency and low cytotoxicity, which has a great potential for application.  相似文献   

17.
18.
??OBJECTIVE To establish a high performance liquid chromatography coupled with tandem mass spectrometry and ultraviolet detector (HPLC-UV-MS) method for determination of the mixture of Glycyrrhiza Radix extract at detoxification dosage and Semen Strychni extract at poisonous dosage, which will be applied to the characteristic ingredients profiling in rat plasma. METHODS Sino Chrome ODS-BP column (4.6 mm??250 mm, 5 ??m) was employed, which was maintained at 40 ??, and the mobile phase was composed of water (0.1% formic acid) (A) and acetonitrile (B). The gradient elution program was as follows: 0.01 min 8% B, 2 min 8% B, 30 min 25% B, 32 min 30% B, 50 min 45% B, 53 min 85% B, 60 min 85% B, 61 min 8% B, and terminated at 77 min, eluted at a flow rate of 0.3 mL??min-1. A UV detector was equipped and the detection wavelength was 254 nm. ESI+ mode was selected for strychnos alkaloids with cone voltage of 30 V and capillary voltage of 2.5 V, while ESI- mode for glycyrrhiza with cone voltage of 25 V and capillary voltage of 3.5 V. Acetonitrile was used as protein precipitation agent to determine the characteristic ingredients in rat plasma. RESULTS An HPLC-UV-MS method for simultaneous determination of liquorice and Semen Strychni extract was established and applied to measure the components absorbed into blood. The material changes of liquorice and Semen Strychni in vivo and vitro were also compared. CONCLUSION A simple, repeatable HPLC-UV-MS method for analysis of Glycyrrhiza Radix and Semen Strychni in vivo and vitro was established. The related components are speculates, which provided the experimental basis to research the detoxification mechanism of Glycyrrhiza Radix against strychninization.  相似文献   

19.
??OBJECTIVE To study the chemical constituents of Catharanthus roseus. METHODS Various column chromatograghic METHODS on silica gel, Rp-18, and Sephadex LH-20 were applied for the isolation and purification of the 95% ethanol extract. The structures were elucidated by their physicochemical properties and spectral data. RESULTS Twenty-two compounds were obtained and identified as ursolic acid (1), daucesterol (2), tetrahydroalstonine (3), 7??-hydroxy-??-sitosterol (4), vindoline (5), ??-sitosterol (6), aurantiamide acetate (7), lochnericine (8), oleanolic acid (9), ajmalicine (10), (22E,24R)-ergosta-7,22-dien-3??,5??,6??-triol (11), betulinic acid (12), stigmasterol (13), quercetin (14), keampferol (15), vindorosine (16), catharanthine (17), diaaurantiamide acetate (18), reserpine (19), panarine (20), serpentine (21), and 16R-E-isositsirikine (22). CONCLUSION Compounds 4, 7, 11, 13, 18, and 20 are isolated from C. roseus for the first time.  相似文献   

20.
??OBJECTIVE To investigate the chemical constituents from the stems of Lythrum salicaria L..METHODS The constituents were isolated and purified by silica gel, Sephadex LH-20 column chromatography, and TLC. The structures were identified on the basis of spectral data and physiochemical characteristics. RESULTS Twenty compounds were isolated from 70% ethanol extracts and identified as betulinic acid(1), 2??,3??,24-trihydroxy-12(13)-en-urs-28-oic acid(2), 6-O-(E)- sinapoylpoligalitol(3), feruloyl-6??-O-??-D-glucopyranoside(4), 7-oxo-??-sitosterol(5), en-tisolariciresinol(6), muramine(7), aesculetin(8), apigenin(9),(2E,6S)-2,6-dimethyl-6-O-??-D-xylpyranosyloxy-2,7-menthiafolic acid(10), quercetin3-O-(6??-caffeoyl)-??-D-galactopyranoside(11), cycloart-23-ene-3??,25-diol(12), (1??S,6??R)-8??-hydroxyabscisic acid-??-D-glucoside(13), 3??,5-dihydroxy-3,6,4??-trimethoxyl-7-O-??-D-glucopyranoside flavonoid(14), aurantiamide acetate(15), 5,6,3??,4??-tetrahydroxy-3,7-dimethoxy-flavone(16), ursolic acid(17), oleanolic acid(18), 4-O-11-methyl-oleoside-p-hydroxyphenyl-(6??-11-methyloleoside)-??-D-glucopyranoside(19), and 6-O-galloylarbutin(20). CONCLUSION Except for compounds 8 and 9, all the compounds were isolated from this plant material for the first time.
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