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The study investigated the effect of Buyang Huanwu Decoction(BYHWD) on endogenous biomarkers in the urine of rats with chronic inflammation induced by lipopolysaccharide(LPS) using ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS), aiming to elucidate the molecular mechanism underlying the therapeutic effect of BYHWD on chronic inflammation from a metabolomics perspective. Male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose BYHWD groups(7.5, 15, and 30 g·kg~(-1)). The model group and BYHWD groups received tail intravenous injection of LPS(200 μg·kg~(-1)) on the first day of each week, followed by oral administration of BYHWD once a day for four consecutive weeks. Urine samples were collected at the end of the administration period, and UPLC-Q-TOF-MS was used to analyze the metabolic profiles of the rat urine in each group. Multivariate statistical analysis methods such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the effect of BYHWD on endogenous metabolites. One-way ANOVA and variable importance for the projection(VIP) were used to screen for potential biomarkers related to chronic inflammation. The identified biomarkers were subjected to pathway and enrichment analysis using MetaboAnalyst 5.0. A total of 25 potential biomarkers were screened and identified in the rat urine in this experiment. Compared with the normal group, the model group showed significant increases in the levels of 14 substances(P<0.05) and significant decreases in the levels of 11 substances(P<0.05). BYHWD was able to effectively reverse the trend of most endogenous biomarkers. Compared with the model group, BYHWD significantly down-regulated 13 biomarkers(P<0.05) and up-regulated 10 biomarkers(P<0.05). The metabolic products were mainly related to the biosynthesis of pantothenic acid and coenzyme A, tryptophan metabolism, retinol metabolism, and propionate metabolism. BYHWD has therapeutic effect on chronic inflammation induced by LPS, which may be related to its ability to improve the levels of endogenous metabolites, enhance the body's anti-inflammatory and antioxidant capabilities, and restore normal metabolic activity.
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Ratas , Masculino , Animales , Cromatografía Líquida de Alta Presión/métodos , Lipopolisacáridos , Ratas Sprague-Dawley , Metabolómica/métodos , Inflamación/tratamiento farmacológico , Biomarcadores/orinaRESUMEN
To investigate the effect of Gegen Qinlian Decoction(GQD) on enzyme activity, gene expression and methylation level of fatty acid synthase(FASN) in adipose tissue from rats with insulin resistance induced by high-fat diet. The 60% fat-powered high-fat diet was continuously given to male SD rats to induce the insulin resistance model. Then, they were divided into five groups randomly and administrated by gavage every day for 16 weeks with following drugs respectively: 10 mL·kg~(-1)water for control group(C) and insulin resistance model control group(IR), 1.65 g·kg~(-1)GQD per day for low-dose group(GQDL), 4.95 g·kg~(-1)GQD per day for medium-dose group(GQDM), 14.85 g·kg~(-1)GQD per day for high-dose group(GQDH), and 5 mg·kg~(-1) rosiglitazone per day for rosiglitazone group(RGN). Epididymal adipose tissue was taken to determine enzyme activity of FASN by colorimetric method, mRNA expression level of Fasn by quantitative Real-time PCR(Q-PCR) and CpGs methylation level between +313 and +582 by bisulfite sequencing PCR(BSP). These results showed that Fasn expression was significantly lowered in IR model rats compared with the control rats(P<0.01). Enzymatic activity and CpGs methylation level of Fasn in IR group showed downward trends. Low and medium-dose GQD can increase enzyme activity of FASN(P<0.05). Moreover, low-dose GQD increased the total CpGs methylation level of Fasn fragment between +313 and +582 in insulin resistance rats(P<0.05). For GQDM group, the methylation frequency of CpGs at positions +506 and +508(P<0.01) as well as the methylation frequency of CpGs on the binding sites of transcription factorzinc finger protein 161(P<0.05) were significantly increased. The methylation frequency of CpG at +442 position was positively correlated with Fasn expression(P<0.01, r=0.735), and methylation frequencies of CpGs at +345 and +366 positions were positively associated to enzyme activity of FASN respectively(P<0.05, r=0.479; P<0.01, r=0.640). In conclusion, GQD can reverse enzyme activity of FASN and methylation level of Fasn in adipose tissue of insulin resistant rats, and CpG sites at positions +506 and +508 may be the targets of GQD. The methylation level of CpGs at + 345 and + 366 sites were possibly related to FASN activity, while methylation of CpG at + 442 site may be closely correlated with mRNA level of Fasn. In addition, GQD did not significantly change mRNA expression level of Fasn, but effectively reversed enzymatic activity, suggesting that GQD may regulate the post transcriptional expression of Fasn.
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Animales , Masculino , Ratas , Tejido Adiposo , Medicamentos Herbarios Chinos , Ácido Graso Sintasas/genética , Expresión Génica , Resistencia a la Insulina/genética , Metilación , Ratas Sprague-DawleyRESUMEN
The resistance and dose limitation of tumors is a serious obstacle to cytotoxic drug therapy in the field of medical oncology. Nitric oxide (NO) is a powerful adjuvant for tumor hypersensitivity for traditional chemotherapy and radiation therapy. The concentration of NO plays an important role in affecting its anti-tumor effect. This review summarizes the mechanism of concentration-dependent effects of NO on tumor cells and the mechanism of chemotherapy sensitization. It provides evidence for rational use of NO to exert anti-tumor effects, and overcoming multidrug resistance and anti-tumor drug development.
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Shenfutang is a famous prescription used in clinic. It has been used for more than one thousand years, and currently is still widely used in clinic, with a significant effect. Shenfutang was first recorded in the Shengji Collection. It consists of two herbs, namely Ginseng Radix Et Rhizoma and Aconiti Lateralis Radix Praeparata. It can be used to mainly treat syncope and collapse due to sudden collapse of Yang Qi, and the symptoms include disfigurement of the extremities, cold sweats, cold limbs, umbilical and abdominal pain, weak breathing, and slight desire. Ginseng supports healthy Qi, and comforts five organs. Aconitum is good at activating twelve meridians and collaterals. With the effect of returning the yang to rescue the enemy, aconitum can also support yang. Different ratios of ginseng and aconitum are combined for reinforcing Yang of heart, kidney and spleen, so as to treat various syndromes. However, the occurrence and development of diseases are complicated and changeable. Different ratios of Shenfutang may increase the efficacy due to the synergistic effect, or weaken or even lose the original efficacy due to mutual antagonism. Different ratios of ginseng and aconitum can be used for different diseases, such as cardiovascular disease, various types of inflammation, respiratory diseases. In the existing literatures on Shenfutang, there is a lack of systematic summarization for how to adjust the ratios. This paper introduces the effect and mechanism of the combination, and summarizes different ratios of the two herbal ingredients, so as to provide certain reference for the clinical application.
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Objective: To identify the chemical constituents of Pinelliae Rhizoma(BX)by ultrahigh-pressure liquid chromatography coupled with electrospray time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Method: Chromatograpic separation was performed on a shim-pack xR-ODS Ⅲ column (2.1 mm×75 mm,1.6 μm) using a gradient elution program with mixtures of acetonitrile and 0.1% formic acid-water as mobile phases at a flow rate of 0.25 mL·min-1. UPLC-Q-TOF-MS/MS was developed for rapid and high-throughput screening of the preliminary chemical profile of BX in positive ion modes. Result: Ninety chemical components were found in BX,according to the accurate Charge-mass Ratio and the MS/MS data,retention time of reference standard,references or databases,the fragmentation regularities of mass spectra. Eighty were identified preliminarily,including 7 alkaloids,8 poly-alcohols,12 fatty glycerides,5 flavonoids,12 lysophosphatidylcholines (LPCs),10 alcohol amines,11 amino acids,11 amides and 4 other type. Conclusion: LPCs were first found in BX. Because BX has certain toxicity,it is found that BX contains LPCs by analyzing the chemical constituents of BX,which can cause inflammatory reaction and neuronal myelin sheath loss and degeneration. Therefore,the analysis of the chemical composition of BX can explain the causes of the toxicity and provide a foundation for the basic research and quality control of the potency of BX.
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Gas chromatography (GC) is mainly used to detect the levels of short-chain fatty acids (SCFAs), but with the deepening of research,the drawbacks of GC have become more and more obvious in the fields of food,chemical engineering and clinical application. The analysis on existing research results showed that ultra performance convergence chromatography (UPC2) was appropriate for the analysis of lipid metabolism. The UPC2 is a new kind of chromatographic separation technology developed in recent five years and the level of SCFAs is associated with the research on multiple diseases. Therefore,application of UPC2 in the detection of SCFAs would be helpful for the scholars at home and abroad to carry out deeper researches,and also helpful to guide the treatment for various metabolic disorders. In this paper,the researches on SCFAs in recent ten years were reviewed; the shortcomings of GC and liquid chromatography (LC) in the detection of SCFAs were reviewed; the development process,basic characteristics and research status of UPC2 at home and abroad were introduced; feasibility and innovation of UPC2 in the detection of SCFAs were summarized. Pretreatment methods for UPC2 application to the detection of SCFAs in feces or serum were collected; the problems that should be noticed during the process of sample pretreatment were pointed out; meanwhile, an research outlook on methodology of UPC2 application in the detection of SCFAs was conducted. The effects of extracting solvent,mobile phase,and auxiliaryt solvent on chromatographic behavior as well as the physicochemical property, type and choice of UPC2 chromatographic column were mainly discussed in this paper. In addition, the choices of basic modifier,acid modifier,and salinity modifier were briefly outlined, in order to provide efficient,simple,environmental,and economic detection technologies for the research on SCFAs, and provide better reference solutions for the rapid detection of massive clinical samples.
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This study was designed to explore the antipyretic mechanism of Pueraria radix. The method of network pharmacology was used to determine the known ingredients corresponding to Pueraria radix, predict the drug-related gene /protein targets, and analyze the interplay between key ingredients and targets. Biological Information Annotation Databases (DAVID) was used to enrich the biological processes and pathways. The result of network analysis was validated by molecular docking. It was found that 49 active ingredients of Pueraria radix not only regulate 21 targets (e.g. PTGS2, EGFR), but also affect 11 biological processes (e.g. oxidation-reduction process, prostaglandin synthesis, positive regulation of fever generation and inflammatory response) and 7 metabolic pathways (arachidonic acid metabolism, serotonergic synapse and HIF-1, et al). Molecular docking results showed that more than 65% of the active ingredients could be well docked with key targets, and the relevant literatures indicated that the active components could inhibit the expression of PTGS2, which means the result has a high reliability. These results indicated that Pueraria radix may carry its pyretic action via a "multi-ingredients-multi-targets-multi-pathways" mode, which provides a scientific basis for further research and drug development.
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OBJECTIVE To explore the biomarkers and molecular mechanism of Huanglianjiedu decoction (HJD) on high fat diet-induced experimental atherosclerosis in rats. METHODS SD male rats were randomly dividedinto five groups(n=8):normal control group,model group,and three dosage groups (1.5, 3 and 6 g crude drug per kilogram of body weight). Atherosclerosis was induced by the combination of regular intraperitoneal injection of vitamin D3and high fat diet for 8 weeks. HJD was administered by oral gavage from the third week once per day and until the end of the study.After the final administration, the blood samples were collected for biochemical analyses [total cholesterol (TC), triglycerides (TG), highdensity lipoprotein (HDL-C), low-density cholesterol (LDL-C)] and blood gas analyses(PaO2, PaCO2, pH, ctHb, etc); the abdominal aorta sections were stained with hematoxylin and eosin for histopathology; the liver homogenate were determined for MDA, SOD, OX-LDL, MCP-1 and VCAM-1.The plasma samples were detected using ultraper formance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS).The data of endogenous compounds were preliminarily preprocessed by software Progenesis QI and then analyzed by multivari-ate statistical analysis software EZinfo 2.0 to screen the distinguished biomarkers and the metabolic pathways were analyzed through website http://www.metaboanalyst.ca/. RESULTS Compared with the normal control group,the content of TC,TG,LDL-C,PaCO2,MDA,Ox-LDL,MCP-1 and VCAM-1were significantly increased and HDL-C, PaO2, ctHb and SOD decreased in the atherosclerosis rats. HJD could significantly attenuated the high fat-induced atherosclerosis pathological injury and the above-mentioned indexes (P<0.05). The five groups could be clearly distinguished using the metabolomics method.The administration groups profile exhibited an apparent returning trend from that of the model group and that of the normal control group.Twenty-one endogenous metabolites has been significantly changed in atherosclerosis rats.HJD could remarkably up-regulate 5-L-glutamyl-taurine,L-beta-aspartyl-L-glutamic acid, histidinyl-hydroxyproline, tryptophyl-alanine, 4′-O-methyl-(-)-epicatechin, and down-regulate protoporphyrin IX,azelaic acid,lacto-N-triaose,cinnamoylglycine and 9′-carboxy-alpha-tocotri-enol. CONCLUSION The beneficial effect of HJD in high fat-induced atherosclerosis rats may be due to anti-oxidant and anti-inflammatory. And it is suggested that HJD may affect the model rats through tryptophan metabolism, taurine and hypotaurine metabolism, histidine metabolism, lysine degradation and porphyrin and chlorophyll metabolism pathway.
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OBJECTIVE To explorethe correlation betweenhypoxiaand insulin resistance bythe blood gas index in high-fat diets-induced obese rat model. METHODS 36% of high-fat diets were fed to SD male rats for 12 weeks. The model group was divided into IR group and non-IR group with the HOMA-IR index of the 12th week,and the abdominal aorta blood was taken for blood gas analysis. RESULTS The HOMA-IR index,Hct,ctHb and ctO2in IR group were significantly higher than those in normal group andnon-IR group(P>0.05),simultaneously no significant difference in pO2,pCO2and sO2 between tree groups.CONCLUSION Circulating blood of obese rat with insulin resistance is normoxia,accompanied by higher Hct,tHb and ctO2,which may be due to the higher blood viscositand the self-regulation of chronic hypoxia in the body.
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OBJECTIVE To investigate the underlyingmechanism on the association of red blood cell and gut microbiota in rats induced by High-Fat Diet(HFD).METHODS A total of 36 male Sprague-Dawley rats (180±20g) were randomly divided into two groups. The control group (n=10) was given a normal chow diet(10% calories of fat),and the High-fat diet group(n=26)was given a HFD(60% calo-ries of fat).We recorded body weight,length and detected serum glucose,serum lipids and insulin ev-ery two weeks.The fresh arterial blood was collected during the experiments and blood gases were measured immediately (Radiometer Medical ApS, Denmark).Thehematocrit (Hct) and partial pressure of oxygen(pO2)were detected by the sensor cassette,following themanufacturer′s instructions.The de-tection method was conductivity measurements and current method, respectively. The feces from ce-cum were analyzed by 16S rRNA gene high-throughput sequencing(Illumina Miseq,USA). RESULTS According to the insulin resistance(IR),body weight and body length,the model group was divided into two small groups.(1)IR group,in which IR,body weight and body length were higher than the control group (P<0.05). (2) un-IR group, body weight and body length were higher than the control group (P<0.05),but the IR was not significantly different.In addition,the levels of hematocrit(Hct),checktotalhe-moglobin (ctHb) and check total blood oxygen content (ctO2) showed significantly increased in the IR group when compared with the control group (P<0.05), however, the pO2was not statistically signifi-cant. Furthermore, we identified that the genus Lactobacillus was moderate positive correlation with Hct,ctHb and ctO2(P<0.05).Compared with the control group,the relative abundance of the Lactoba-cillus was significantly lower in IR group(P<0.05).CONCLUSION The high-fat diet induced rats′local tissue hypoxia under the red blood cell increasing,oxygen partial pressure constant and the reduction of Lactobacillus′abundance might be caused by aerobic oxidation and glycolysis inhibition in the meantime.
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<p><b>OBJECTIVE</b>To investigate the impact of dampness-heat (DH) on the development of mammary tumors in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rats.</p><p><b>METHODS</b>Forty rats were randomly divided into 3 groups in a randomized block design, including the control group (n=13), DMBA group (n=14), and DMBA plus DH group (n=13). Rats in the DMBA group and DMBA plus DH group were intragastrically administrated with DMBA (100 mg/kg) for twice, once per week, while rats in the control group were treated with equivalent volumes of sesame oil. After DMBA administration, rats in the DMBA plus DH group were exposed to a simulated climate chamber with ambient temperature (33.0±0.5°C) and humidity (90%±5%) for 8 weeks, 8 h per day. The body weight, time of tumor formation, and number of tumors were measured weekly to calculate tumor incidence, average latency period, average number of tumors, and average tumor weight. At the end of the experiment, the levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in serum, and the contents of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β in serum and tumor tissue were measured, respectively. Some tumor tissues were processed for hematoxylin-eosin staining to determine the histopathological changes.</p><p><b>RESULTS</b>Compared with DMBA, DMBA plus DH significantly increased the average number of tumors, average tumor weight, levels of serum MMP-9, TIMP-1, TNF-α and IL-1β, and contents of tumor tissue TNF-α and IL-1β (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>DH could accelerate the development of mammary tumors through increasing the expressions of MMP-9, TIMP-1, TNF-α and IL-1β in DMBA-induced rats.</p>
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Adipocytokines are closely associated with insulin resistance (IR) in adipose tissues, and they are more and more seriously taken in the study of the development of diabetes. This experiment was mainly to study the effect of berberine on mRNA expression levels of PPARγ and adipocytokines in insulin resistant adipocytes, and investigate the molecular mechanism of berberine in enhancing insulin sensitization and application advantages of droplet digital PCR (ddPCR). ddPCR absolute quantification analysis was taken in this experiment to simply and intuitively determine the appropriate reference genes. ddPCR and quantitative Real-time PCR (qPCR) were used to compare the effect of different doses of berberine (10, 20, 50, 100 μmol•L⁻¹) on mRNA expression levels of PPARγ, adiponectin, resistin and leptin in IR 3T3-L1adipocytes. Antagonist GW9662 was added to study the inherent correlation between PPARγ and adiponectin mRNA expression levels. ddPCR results showed that the expression level of β-actin in adipocytes was stable, and suitable as reference gene for normalization of quantitative PCR data. Both of ddPCR and qPCR results showed that, as compared with IR models, the mRNA expression levels of adiponectin were decreased in the treatment with berberine (10, 20, 50, 100 μmol•L⁻¹) in a dose-dependent manner (P<0.01); the expression of PPARγ was decreased by 20, 50, 100 μmol•L⁻¹ berberine in a dose-dependent manner in qPCR assay (P<0.01) and decreased only by 50 and 100 μmol•L⁻¹ berberine in ddPCR assay (P<0.05). PPARγ specific antagonist GW9662 intervention experiment showed that adiponectin gene expression was directly relevant with PPARγ (P<0.05). ddPCR probe assay showed that various doses of berberine could significantly reduce mRNA expression levels of resistin and leptin (P<0.01) in a dose-dependent manner. In conclusion, berberine enhanced insulin sensitization effect not by up-regulating adiponect in expression of transcriptional level in PPARγ-dependent manner, but may by the elevated multimerization of adiponectin in the posttranslational regulation level. Berberine down-regulated the resistin and leptin expression levels, which could alleviate lipolysis and improve IR in adipocytes. ddPCR provided better sensitivity and linear range than qPCR, with obvious technical advantages for the detection of low abundance expression of target genes.
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Proteomics method, based on NanoLC-LTQ-Orbitrap technology, was applied to explore the biological basis of intervention effect of "Qi enriching" herbs on "Qi deficiency" rats. The "Qi deficiency" rat model was established with caloric restriction combined with excessive swimming. Muscle proteins of vastus lateralis from the blank group, the model group and the ginseng group were detected by NanoLC-LTQ-Orbitrap system. The data were imported into Protein Discovery software to identify the proteins and all the raw datum were analyzed by SIEVE software. Compared with model group, 26 significant difference proteins were found in ginseng group, which the variation trend was consistent with the blank group. Through the biological function analysis, the found proteins could be classified into proteins involved in energy metabolism, proteins involved in glucose metabolism, electrolyte balance and material transfer related proteins, inflammation related protein and cytoskeleton protein. The above target proteins and their regulation pathways may be the biological basis which ginseng played a role of tonifying "Qi" of "Qi deficiency" symptom.
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This study aimed to explore the mechanism of Chinese traditional medicine, Kudzu root(Chinese name:Ge-Gen; Latin name: Puerariae Lobatae Radix) how to improving insulin resistance (IR) through the regulation of the glucose and lipid metabolism in the IR-3T3-L1 adipocytes. After the 3T3-L1 mouse preadipocytes were differentiated into mature adipocytes, IR model(IR-3T3-L1) was built with 1 μmol•L-1 dexamethasone treatment for 96 h. IR adipocytes were treated with different concentrations (5%,10% and 15%) of Ge-Gen containing serum (GG-CS)for 12 h or 24 h, whereas rosiglitazone group as positive control in this study. The glucose contents in cell culture supernatants were detected by glucose oxidase assay and the intracellular triglyceride (TG) contents were measured by glycerol phosphate oxidase assay respectively.The mRNA expression levels of PPARγ, ADPN, GLUT4, LPL, FABP4 and FASn gene were determined by real-time quantitative PCR(qPCR).Results showed that IR-3T3-L1 adipocytes significantly increased glucose consumption (P<0.01)and decreased TG contents (P<0.01) as compared with the normal control group, the glucose consumption significantly increased with the treatment of GG-CS (P<0.01) by dose-dependent and time-dependent manners,whereas the intracellular TG content was sigificantly decreased (P<0.01) by dose-dependent manner.qPCR analysis revealed that 10% and 15% GG-CS significantly up-regulated the mRNA expression level of PPARγ, ADPN and GLUT4 (P<0.01) with the same dose-dependent manner,whereas the GLUT4 mRNA expression was showed similar expression pattern with the treatment of 10% and 15% GG-CS (P<0.01).We also detected the mRNA expression levels of several important lipid-metabolizing enzymes such as LPL, FASn and FABP4 by PPARγ regulation. 15% GG-CS elevated LPL mRNA expression (P<0.05);10% and 15% GG-CS enhanced the FASn mRNA expression (P<0.01), whereas 5%,10% and 15% GG-CS down-regulated FABP4 mRNA expression (P<0.01). Together, our results indicated that GG could regulate the glucose and lipid metabolism to ameliorate IR with multi-target manners in 3T3-L1 adipocytes.
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To establish a HPLC method for simultaneously determining plasma concentrations of gastrodin (Gas) and its metabolites hydroxybenzyl alcohol (HBA), puerarin (Pur) and internal standard (IS) p-hydroxyphenylethanol (Tyr) in rats and studying the pharmacokinetic process and interactions of gastrodin and puerarin after single and combined intravenous injection and oral administration. With Tyr as the internal standard, plasma samples were processed with methanol for protein precipitation, supernatant was dried with N2, and residues were re-dissolved with acetonitrile-0.05% phosphoric acid (20: 80). Chromatography was carried out on an Agilent ZORBAX SB-Aq C18 column (4.6 mm x 250 mm, 5 μm), with acetonitrile-0.05% phosphoric acid as the gradient mobile phase for the gradient elution. The UV detector wavelength was set at 221 nm for Gas HBA and IS and 250 nm for Pur. After the single or combined administration of Gas and Pur, their plasma concentrations in rats were detected. WinNonlin 5.2 pharmacokinetic software and SPSS 17. 0 software were used to respectively calculate pharmacokinetic parameters of each group, make a statistical analysis and compare the pharmacokinetic processes of Gas and Pur after the single or combined administration. According to the results, the absolute recoveries between low, media and high concentrations of Gas, HBA and Pur and IS as well as Tyr were more than 77.20%, with a good linearity (r > 0.999 6, n = 5) for Gas, HBA and Pur within concentration ranges of 0.10-101, 0.03-7.58 and 0.05-5.98 mg xL ('1) respectively. The lower limits of quantification for Gas, HBA and Pur were 0.10, 0.03, 0.05 mg x L(-1), respectively. Their in-ra-day and inter-day precisions were less than 12% with the accuracy between 85. 1% -1 10. %. All of the three substances and IS were stable during the whole analysis process. The findings showed significant differences in the main in vivo pharmacokinetic parame-ers in rats (AUC, C.(max) T,½ T.(max) MRT) after the single and combined administration of Gas and Pur. Either after the oral adminis-ration or after the intravenous injection, parameters showed a lower clearance rate ( L) longer mean residence time ( RT) and higher relative bioavailability, especially after the oral administration. Specifically, the relative bioavailability of the combined oral ad-inistration of Pur was 10. 7 times of that of the single administration, while that of Gas was 1. times of that of the single administra-ion. The combined administration of Gas and Pur can promote the absorption, decrease the elimination rate and prolong the mean resi-ence time. The method is simple and accurate and can be applied in the simultaneous determination of plasma concentrations of Gas, HBA and Pur in rats and the pharmacokinetic studies.
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Animales , Masculino , Ratas , Administración Oral , Alcoholes Bencílicos , Sangre , Farmacocinética , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos , Farmacocinética , Glucósidos , Sangre , Farmacocinética , Isoflavonas , Sangre , Farmacocinética , Ratas WistarRESUMEN
To establish a LC-MS/MS method to determine the concentrations of liquiritin, glycyrrhizin, glycyrrhetinic acid, amygdalin, amygdalin prunasin, ephedrine, pseudoephedrine and methylephedrine of Maxing Shigan decoction in rat plasma, and study the differences on their pharmacokinetic process in normal rats and RSV pneumonia model rats. After normal rats and RSV pneumonia model rats were orally administered with Maxing Shigan decoction, the blood was collected from retinal vein plexus of different time points. Specifically, tetrahydropalmatine was taken as internal standard for determining ephedrine, while chloramphenicol was taken as internal standard for determining other components. After plasma samples were pre-treated as the above, the supernatant was dried with nitrogen blowing concentrator and then redissolved with methylalcohol. The chromatography was eluted with mobile phase consisted of acetonitrile and 0.1% formic acid solution in a gradient manner. ESI sources were adopted to scan ingredients in ephedra in a positive ion scanning mode and other ingredientsin a negative ion scanning mode. The multiple-reaction monitoring (MRM) method was developed the plasma concentration of each active component. The pharmacokinetic parameters of each group were calculated by using Win-Nonlin 4.1 software and put into the statistical analysis. The result showed the plasma concentration of the eight active ingredients, i.e., liquiritin, glycyrrhizin, glycyrrhetinic acid, amygdalin, amygdalin prunasin, ephedrine, pseudoephedrine and methylephedrine within the ranges of 1.04-1040, 1.04-1040, 0.89-445, 1.05-4200, 1.25-2490, 0.3-480, 0.3-480, 0.3-480 microg x L(-1), with a good linearity and satisfactory precision, recovery and stability in the above ingredients. After modeling, except for glycyrrhetinic acid whose pharmacokinetic parameters were lacked due to the data missing, all of the rest components showed significant higher Cmax, AUC(0-1) and lower clearance rate (CL) than that of the normal group, indicating the increase in absorption in rats in the pathological state by reducing the clearance rate. The method is accurate and sensitive and so can be used to determine the plasma concentrations of the eight active ingredients in Maxing Shigan decoction. RSV pneumonia-infected rats absorbed more ingredients in Maxing Shigan decoction.
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Animales , Masculino , Ratas , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Farmacocinética , Neumonía Viral , Quimioterapia , Metabolismo , Ratas Sprague-Dawley , Infecciones por Virus Sincitial Respiratorio , Quimioterapia , Metabolismo , Espectrometría de Masas en TándemRESUMEN
<p><b>OBJECTIVE</b>To observe the effect of the modified artificial esophagus on postoperative stenosis in dogs.</p><p><b>METHODS</b>The models of defected esophagus were established in dogs. The double-layered membrane tube (modifying type) was implanted in the test group (n = 10) and the esophageal stent was further inserted when the stenosis occurred. The single pattern tube (original type) was transplanted to the control group (n = 30). The dilation treatment was performed to relieve the postoperative stenosis; alternatively, the esophageal stent was implanted in the unsuccessful dogs.</p><p><b>RESULTS</b>The average artificial esophagus removal time was 19.10 days in the test group, which was significantly lower than 39.07 days in the control group (t = 15.6, P = 0.000). No obstruction after removal was observed in the experimental group. The incidence of postoperative stenosis had no significant difference between these two groups.</p><p><b>CONCLUSION</b>The double-layered membrane tube can make the tube removal safer by shortening the removal time.</p>
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Animales , Perros , Femenino , Masculino , Órganos Artificiales , Estenosis Esofágica , Esofagectomía , Esófago , Trasplante , Complicaciones Posoperatorias , Distribución AleatoriaRESUMEN
<p><b>OBJECTIVE</b>To evaluate the effect of high intensity focused ultrasound (HIFU) for liver cancer.</p><p><b>METHODS</b>HIFU treatment was performed in 44 liver cancer patients under general anesthesia and ultrasound positioning. Before and after HIFU treatment, the clinical symptoms, liver functional tests, AFP and MRI were evaluated.</p><p><b>RESULTS</b>After HIFU treatment, the remission rate of clinical symptoms was 87.5% (28/32), with the scanty ascites in 3 patients disappeared. ALT (79.73 +/- 12.31 U/L) and AST (103.47 +/- 24.55 U/L) before HIFU were reduced to normal in 84.6% (22/26) and 73.5% (25/34) patients. AFP in 64.3% (18/28) patients decreased > or = 50% of the original value. After HIFU, MRI showed coagulative necrosis and blood supply reduction or disappearance of tumor in the target region.</p><p><b>CONCLUSION</b>HIFU treatment pocesses good effect on liver cancer, which will offer a considerable weight in noninvasive local treatment of hepatic tumor.</p>