Alterations of gut microbiota composition and cogni-tive behavior in APP/PS1/tau triple-transgenic mouse model of Alzheimer's disease / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer's disease(AD)is a progressive neurological disease.Given the important role of gut microbiota composition in AD pathology,the observed perturbation in the microbiota composition and diversity may serve as the mechanisms underlying age-dependent APP/PS1/tau triple-transgenic mouse(3×Tg-AD)mice amyloid deposition and memory deficits.Here-in,we intended to investigate the gut microbiota and as-sessed its relationship with the triggering and develop-ment of cognitive impairment of AD.METHODS This study involves the comparative assessment of spatial learning,amyloid β-protein(Aβ)accumulation,and fecal microbiota alterations in 3×Tg-AD mice from three age groups:AD asymptomatic stage(3 m),presymptomatic stage(6 m),and the symptomatic stage of AD(9 m).RE-SULTS We demonstrate that spatial memory deficits,brain Aβ accumulation,and weight gain in 3×Tg-AD mice gradually appear after 6 months of age.However,the total gut bacterial counts underwent changes from 3 to 6 months of age and were further altered at 9 months of age.Importantly,changes in gut bacteria abundance of Desulfobacterota and Actinobacteriota phylain 6-month-old mice preceded apparent spatial memory deficits.CONCLUSION Changes in the gut microbial community are one of the mechanisms of early AD pathology.

Protective effect of gastrodin on A β 25-35-induced HT22 cell injury by improving glycolytic function through activating PI3K/Akt/BACH1 signaling axis / 中国药理学与毒理学杂志

OBJECTIVE To investigate whether gas-trodin(GAS)plays a neuroprotective role by activating PI3K/Akt/BACH1 signaling axis to improve glycolytic func-tion.METHODS HT22 cells were treated with Aβ25-35 for 24 h to establish cell damage model.GAS pretreated HT22 cells for 2 h,and Akt agonist SC79,Akt inhibitor MK2206,PI3K inhibitor LY294002 were added 0.5 h before GAS treatment to detect their protective mecha-nisms.Pharmacodynamic research of GAS in this model were divided into six groups:control group,GAS group(GAS 10 μmol·L-1),model group(Aβ25-35 20 μmol·L-1),model +GAS 2.5,5 and 10 μ mol·L-1 group).Mecha-nism research of GAS in this model was divided into 6 groups:control group,Aβ25-35 20 μmol·L-1 group,Aβ25-35 20 μmol·L-1 + GAS 10 μmol·L-1 group,Aβ25-35 + SC79 group(Aβ25-35 20 μmol·L-1 +SC79 10 μmol·L-1),Aβ25-35+MK2206+GAS group(A β 25-35 20 μ mol·L-1 +MK2206 10 μmol·L-1+GAS 10 μmol·L-1),Aβ25-35+LY294002+GAS group(Aβ25-35 20 μmol·L-1+LY294002 10 μmol·L-1+GAS 10 μmol·L-1).Cell viability was detected by MTT,mor-phological changes of cells were observed by micro-scope,ATP content was detected by chemilumines-cence,and pyruvate(PA)content was detected by colo-rimetry.Western blotting was used to detect the protein levels of transcription factor BACH1,key glycolysis enzyme hexokinase(HK1)and PI3K/Akt signaling path-way related proteins PI3K,p-PI3K,Akt and p-Akt.RESULTS The results showed that compared with the control group,the cell morphology of HT22 cells damaged by Aβ25-35 was damaged,the number of cells decreased,the cell body became smaller,the number of dead cells increased,the cell survival rate,ATP and PA contents decreased significantly,and the protein expressions of p-PI3K,p-Akt,BACH1 and HK1 were significantly down-regulated.GAS treatmentcansignificantlyimprovethemor-phology of HT22 cells damaged by Aβ25-35,increase cell survival rate,ATP and PA contents,and up-regulate the expression of p-PI3K,p-Akt,BACH1 and HK1 proteins.SC79 also significantly increased cell survival rate,ATP content,protein expression of BACH1 and HK1.However,the above ameliorative effect of GAS on HT22 cell dam-age induced by Aβ25-35 was antagonized by LY294002 and MK2206.CONCLUSION GAS exerts a neuroprotec-tive effect on Aβ25-35-induced HT22 cell injury by improv-ing glycolytic function through activating PI3K/Akt/BACH1 signaling axis.

Research progress on molecular mechanisms of angiogenesis after acute myocardial infarction / 中国比较医学杂志

Angiogenesis is a process that new blood vessels generate on the basis of an original vascular plexus via sprouting or other forms during normal growth and development of an organism or under particular conditions such as wound repairing and ischemic hypoxia. In general, angiogenesis includes five stages: degradation of the vascular basement membrane, endothelial cell proliferation, vascular sprouting, lumen formation and vascular network turning stable and mature. Among ischemic heart diseases, acute myocardial infarction seriously threatens human health, its pathological characteristics include myocardial vascular stenosis and blockage,leading to myocardial infarction. Therefore,the promotion of angiogenesis has become one of the therapies for ischemic heart diseases. A variety of pro-angiogenic cytokines are involved in the process of angiogenesis, such as polypeptide growth factors and lipid mediators. In this paper we review the recent progress in research on the expression of pro-angiogenic factors in myocardium after ischemic myocardial infarction.

Protective effects of NDP on LPS induced neuron injuries in rat mixed cultures / 中国药理学通报

Aim To investigate the protective effect of noble dendrobium polysaccharides ( NDP ) on lipopo-lysaccharide ( LPS)-induced neuron injuries in newborn rat cerebral cortex glial cells and neuron mixed cul-tures.Methods The primary cultures of newborn rat cortical neurons and glial cells were established and the existence of the neurons , astrocytes and microglia was verified respectively .NDP was given to LPS-induced mixed cultures , the mRNA levels of IL-1β, TNF-αand COX-2 were assayed by real time PCR .Results NDP reduced the glial cell activation and neuron dam-age after it was given to LPS-induced mixed cultures . The mRNA levels of IL-1β, TNF-α, COX-2 were re-duced .Conclusion NDP protects against LPS-in-duced neuron-inflammation in neurons and glial cells cultures.

Antioxidative effect of total ginsenosides on exprimental pulmonary fibrosis of mice / 中国药理学与毒理学杂志

OBJECTIVE To observe the protective effect and underlying mechanism of total ginsenosides (TG) on bleomycin-induced pulmonary fibrosis. METHODS Intratracheal instillation of bleomycin 5 mg · kg-1 was conducted to establish a pulmonary fibrosis mouse model. Kunming mice(1/2 males and 1/2 females)were randomly divided into sham-operation(Sham),model,total ginsen?osides 40,80 and 160 mg·kg-1 and prednisone acetate(5 mg·kg-1) groups. After 28 d administration,the histopathological changes in the lung were analyzed by hematoxylin eosin(HE)and Masson staining. The exprssion of alpha smooth muscle actin(α-SMA)in the lung was detected by real-time PCR. The content of hydroxyproline(HYP)and glutathione(GSH),level of total antioxidant capacity(T-AOC)and hydroxy radical(·OH),activity of myeloperoxidase(MPO)and nitric oxide synthase(NOS)in the lung were detected by corresponding kits. RESULTS Compared with the sham group,the pulmonary indexes in model group were significantly increased(P<0.01),alveolitis and pulmonary fibrosis were obvious. The mRNA expression ofα-SMA,content of HYP and · OH,activity of MPO and NOS were increased(P<0.05),but the content of GSH and T-AOC in model group was decreased(P<0.05). Compared with model group,the pulmonary indexes in TG 80 and 160 mg · kg-1 and prednisone acetate 5 mg · kg-1 groups were reduced(P<0.05),and the degree of alveolitis and pulmonary fibrosis was mitigated. The mRNA expression ofα-SMA,content of HYP and · OH, the activity of MPO and NO were decreased (P<0.05),while the content of GSH and T-AOC was increased(P<0.05). CONCLUSION TG can improve the degree of mice pulmonary fibrosis induced by bleomycin. The mechanism may be related to the increased antioxidant capacity of organisms.

Cryptotanshinone inhibits TNF-α-induced LOX-1 expression by suppressing reactive oxygen species (ROS) formation in endothelial cells

Cryptotanshinone (CPT) is a natural compound isolated from traditional Chinese medicine Salvia miltiorrhiza Bunge. In the present study, the regulatory effect and potential mechanisms of CPT on tumor necrosis factor alpha (TNF-α) induced lectin-like receptor for oxidized low density lipoprotein (LOX-1) were investigated. Human umbilical vein endothelial cells (HUVECs) were cultured and the effect of TNF-α on LOX-1 expression at mRNA and protein levels was determined by Real-time PCR and Western blotting respectively. The formation of intracellular ROS was determined with fluorescence probe CM-DCFH2-DA. The endothelial ox-LDL uptake was evaluated with DiI-ox-LDL. The effect of CPT on LOX-1 expression was also evaluated with SD rats. TNF-α induced LOX-1 expression in a dose- and time-dependent manner in endothelial cells. TNF-α induced ROS formation, phosphorylation of NF-κB p65 and ERK, and LOX-1 expression, which were suppressed by rotenone, DPI, NAC, and CPT. NF-κB inhibitor BAY11-7082 and ERK inhibitor PD98059 inhibited TNF-α-induced LOX-1 expression. CPT and NAC suppressed TNF-α-induced LOX-1 expression and phosphorylation of NF-κB p65 and ERK in rat aorta. These data suggested that TNF-α induced LOX-1 expression via ROS activated NF-κB/ERK pathway, which could be inhibited by CPT. This study provides new insights for the anti-atherosclerotic effect of CPT.

Analysis of Piper puberulum (Benth.) Maxim.extracts preparation and the preliminary qualitative chemical composition / 中国生化药物杂志

Objective To investigate optimal extraction process of Piper puberulum ( Benth.) Maxim.and qualitative analyze the chemical component of the extracts.Methods Method of solvent heating reflux was used for extraction.On the basis of single factor experiment, L9 (34 ) orthogonal experiment was designed with the variants of extraction frequency, time, material-liquid ratio, and immersion time.Extraction rate as index, extraction processes were optimized to achieve best extraction.The extracts, including total extract, water elution, and ethanol elution, were physiochemically analysed to achieve an initial qualitative result.Results The optimal extraction process was: extractions 3 times for 2 hours, with an 1︰30 material -liquid ratio and 2 hours of immersion, Initial qualitative analyzed the total extracts containing amino acids, polypeptides, proteins, alkaloids, steroids or triterpenes, flavones, saponins, polysaccharides, reducing sugars or glucosides, cumarins, terpene lactones, phenols, and tannins.The water elution containing: amino acids, polypeptides, proteins, saponins, polysaccharides, reducing sugars or glucosides, cumarins, and terpene lactones.The ethanol elution containing: amino acids, polypeptides, proteins, alkaloids, steroids or triterpenes, flavones, polysaccharides, reducing sugars or glucosides, phenols, and tanins.Conclusion The experiments show that optimal extraction process can achieve high extraction yield, stable and practical.

The effects of tetrahydroxystilbene glucoside on mouse liver cytochrome P 450 / 重庆医学

Objective To investigate the effects of tetrahydroxystilbene glucoside (TSG) on cytochrome P450(CYP) in mouse livers .Methods Kunming male mice were divided into the blank ,low dose and the high dose of TSG groups .3 ,5 and 7 after intra-gastrical administration of TSG ,mice were sacrificed and the mRNA expressions of CYP isoenzymes in mouse livers were measured by real time reverse transcription-polymerase chain reaction(RT-PCR) ,respectively .Results TSG significantly inhibited CYP1A2 and CYP 3A4 mRNA expressions at 3th ,5th and 7th day after treatment .TSG time-dependently increased CYP2E1 mRNA expres-sion .TSG inhibited CYP4A14 mRNA expression at 7th day after treatment .Moreover ,TSG had no significant effects on CYP2B10 , CYP3A11 and CYP3A25 mRNA expressions .Conclusion TSG has significant effects on CYP1A2 ,CYP2E1 ,CYP3A4 and CYP4A14 mRNA expressions but no significant effects on CYP2B10 ,CYP3A11 and CYP3A25 mRNA expressions .

Safety evaluation of realgar-and cinnabar-containing traditional Chinese medicine / 中国中药杂志

Realgar (90% of AS4S4) and cinnabar (96% of HgS) have been used in traditional Chinese medicines for thousands of years. Both arsenic and mercury are well-known for toxic effects and the safety of realgar-and cinnabar-containing traditional Chinese medicines is of concern. It is considered that any intentional use of known toxic metals in medicine is an unacceptable risk, while an opposing opinion presumes that realgar and cinnabar have clear pharmacological action with tolerable side effects. This review summarized the progress of toxicological study on realgar-and cinnbar-containing traditional Chinese medicines.

Apoptosis inducing effect of tanshinone II(A) on human nasopharyngeal carcinoma CNE cells / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate anticancer effect and potential mechanism of tanshinone II(A) (Tan II(A)) on human nasopharyngeal carcinoma cell line CNE cells.</p><p><b>METHOD</b>Antiproliferative effect of Tan II(A) on CNE cells was evaluated by morphological examination, cell growth curves, colonial assay and MTT assay. Apoptosis detection was carried out using Hoechest 33258 and PI double-dyeing method. Intracellular Ca2+ concentration and mitochondria membrane potential were detected by fluorospectrophotometer. Bad and MT-1A transcript analysis in CNE cells was analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR).</p><p><b>RESULT</b>Tan II(A) could inhibit CNE cells proliferation in dose- and time-dependent manner. 50% inhibiting concentration of Tan II(A) on CNE cells in 24, 48, 72 h was 45.7, 24.8, 3.3 mg x L(-2), respectively. Typical apoptotic morphology such as chromatin aggregation was observed in CNE cells with Tan II(A) treated for 24 h, and the apoptotic inducing effect was in a dose-dependent manner. After treated with Tan II(A), intracellular Ca2+ concentration of CNE cells was increased, mitochondria membrane potential of the cells was decreased, relative mRNA level of Bad and MT-1A was up-regulated.</p><p><b>CONCLUSION</b>Tan II(A) had anticancer effect on CNE cells through apoptosis via calcineurin-dependent pathway and MT-1A downregulation.</p>

Realgar is active ingredient of Angong Niuhuang pill in protection against LPS-induced neuroinflammation / 中国中药杂志

<p><b>OBJECTIVE</b>To determine the effects of Angong Niuhuang pill (AGNHW) on lipopolysaccharide (LPS)-induced neuroinflammation and further to investigate the role of realgar and cinnabar on AGNHW-mediated neuroprotection.</p><p><b>METHOD</b>Primary rat midbrain neuron-glia cultures were used as an in vitro model to examine the effects of AGNHW on LPS-induced dopamine (DA) neuronal damage. Cultures were divided randomly into five groups: control, LPS, LPS plus AGNHW, LPS plus realgar and LPS plus cinnabar. Dopaminergic neurotoxicity was measured by [3H] DA uptake assay. The production of intracellular reactive oxygen species (ROS) was quantified via the DCFH-DA probe. Real-time RT-PCR was applied to detect the mRNA expression of pro-inflammatory factors. Then the protein levels of these factors were determined by ELISA and western blot assay.</p><p><b>RESULT</b>Compared with the control group, LPS apparently decreased DA uptake capacity (P < 0.05); induced the production of intracellular ROS (P < 0.05); enhanced the mRNA expression of TNF-alpha, iNOS, IL-13 and COX-2 (P < 0.05) and the release of TNF-alpha, IL-1beta and PGE2 in the supernatant of cultures (P < 0.05); and also increased the level of iNOS protein (P < 0.05). Compared with the LPS group, AGNHW and realgar significantly inhibited LPS-induced reduction of DA uptake (P < 0.05); attenuated the production of intracellular ROS (P < 0.05) and the mRNA expression of TNF-alpha, iNOS, IL-1beta and COX-2 (P < 0.05) and the release of TNF-alpha, IL-1beta and PGE2 (P < 0.05) and the level of iNOS protein (P < 0.05). However, there was no significant difference between LPS group and LPS plus cinnabar group.</p><p><b>CONCLUSION</b>AGNHW is effective in protecting against LPS-induced neuroinflammation, and realgar is one of active components for AGNHW to produce anti-inflammatory effects.</p>

Effect of Angong Niuhuang Wan, cinnabar and realgar against lipopolysaccharide-mediated neurotoxicity / 中国药理学与毒理学杂志

OBJECTIVE To investigate the role of cinnabar and realgar in Angong Niuhuang Wan (AGNH) -produced neuroprotection against lipopolysaccharide ( LPS) -mediated neuronal damage and further explore the corresponding mechanisms. METHODS Primary rat midbrain neuron-glia cultures were used as an in vitro model to investigate effects of AGNH on LPS-mediated degeneration of dopamine (DA) neurons. The experiment was divided into normal control group, LPS model group, LPS + cinnabar (4 and 40 mg·L-1) groups, LPS + realgar (4 and 40 mg·L-1 ) groups and LPS + AGNH (40 and 400 mg·L-1 ) group. Drugs were added 30 min before LPS treatment. After 7 d, dopaminergic neurotoxicity was assessed through the quantification of tyrosine hydroxylase (TH)-positive neurons and morphological analysis of TH-positive neurons; the activation of microglia was evaluated using OX-42 antibody; the gene expression of tumor necrosis factor-α (TNF-α) and induced nitric oxide synthase (iNOS) mRNA in microglia was performed by real-time RT-PCR analysis, and the release of TNF-α and nitric oxide (NO) in the supernatant of neuron-glia cultures was determined respectively by the ELISA and Griess reagent. RESULTS Compared with normal control group, DA neurons in LPS model group decreased by 40% (P <0.05) , microglial activation was induced, the expression of TNF-α mRNA and iNOS mRNA in microglia increased 9 and 2 times, respectively ( P < 0. 05 ) , and subsequent production of TNF-α and NO in the supernatant of neuron-glia cultures increased 20 and 30 times, respectively (P<0.05). Compared with LPS model group, AGNH 400 mg·L-1 and realgar 40 mg·L-1 significantly attenuated LPS-mediated DA neuronal loss by 40% and 30% , respectively (P<0.05) and inhibited activation of microglia and expression of TNF-α mRNA by 61% and 52% (P <0.05). iNOS mRNA was reduced by 58% and 51% (P <0.05 ) in microglia. The subsequent release of TNF-α was reduced by 55% and 43% (P<0.05) and NO reduced by 53% and 34% (P<0.05) in the supernatant of neuron-glia cultures. Cinnabar had no inhibitory effect on LPS-induced changes. CONCLUSION AGNH protects LPS-induced neurotoxicity through its anti-inflammatory properties and realgar might be the key contributor to the neuroprotective action of AGNH, while cinnabar fails to show any neuroprotection.

Neuroprotective effect of taurine against acute cortical neuron injury induced by oxygen-glucose deprivation / 中国药理学与毒理学杂志

AIM Taurine was reported neuroprotective under several ischemic models in vivo. In this study, the direct effect of taurine against oxygen-glucose deprivation (OGD) inducing acute neuronal injury and the underlying mechanisms in vitro were investigated. METHODSFour hours OGD was used to induce in vitro ischemic injury in rat cortical neurons. Taurine 5, 10 and 20 mmol·L-1 was added 20 h before and during 4 h OGD period respectively. Mortality rate of neuron was assayed by MTT and flow cytometry methods. Level of neuronal [Ca2+]i was detected by Fura 2/AM loading. Amino acid concentrations in culture media were measured by high performance liquid chromatography. RESULTS Under OGD conditions, neuronal death was markedly increased, and the levels of neuronal [Ca2+]i and extracellular glutamate level were enhanced obviously. Taurine pretreatment obviously decreased the percentage of neuronal death induced by OGD. In addition, abnormal elevation of neuronal [Ca2+]i and extracellular glutamate level induced by OGD both were markedly repressed by taurine. CONCLUSION Taurine can alleviate rat cortical neuron injury induced by OGD, the mechanisms were likely due to repressing calcium overload and inhibiting excessive release or leakage of glutamate under such conditions.

Inhibitory effect of anticomplementary protein atrase B from cobra venom on platelet aggregation induced by activated complement / 中国药理学通报

Aim To investigate the inhibitory effect of atrase B on human platelet aggregation induced by activated complement.Methods By employing CVF to activate complement,the effect of atrase B on gel filtered platelet aggregation induced by activated complement was measured by turbidimetry and the expression of P-selectin and GPⅡb/Ⅲa on platelet membrane were detected by flow cytometry.Results Atrase B inhibited platelet aggregation and the expression of P-selectin and GPⅡb/Ⅲa on platelet membrane induced by activated complement.Conclusion Anticomplementary protein atrase B from Naja atra venom can significantly inhibit platelet activation and aggregation induced by activated complement.

Inhibitory effect of Isorhynchophylline on platelet aggregation and thrombosis / 中国药理学通报

Aim To investigate the effect of Isorhynchophylline(Isorhy)on platelet aggregation or thrombosis,and explore the mechanism of it's action.Methods Rat platelet aggregation was determined.cAMP contents were assessed by Born's method and radioimmunoassay respectively.The effect of Isorhy on rat's thrombosis was observed with the thrombogenesis model of artery-vein bypass.Results Isorhy(0.65 mmol?L-1,1.30 mmol?L-1)was shown to markedly inhibit the rat's platelet aggregation induced by ADP or thrombin in a concentration-dependent manner(P

Effect of protopine on contraction and intracellular free calcium concentration of smooth muscle of thoracic aorta in rats / 第三军医大学学报

Objective To study the effect of protopine (Pro) on the intracellular free calcium ions of the smooth muscular cells of the thoracic aorta in rats. Methods The procedure of calcium absence-calcium addition was designed to observe the changes of the level of calcium ions in the strips of the smooth muscle of the thoracic aorta indirectly. The concentration of calcium ions in the smooth muscle of the thoracic aorta was determined with Fura-2/AM loaded SMCs. The elevation of calcium ions was induced with norepinephrine (NE). The concentration of potassium ions was observed in the presence of Pro. Results Pro significantly inhibited the NE-induced transient contract of the smooth muscle of the thoracic aorta in calcium-free medium and long-lasting contraction after the addition of calcium ions in a concentration-dependent manner. In Fura-2/AM loaded SMCs, Pro (50 ?mol/L or 100 ?mol/L) exerted no effect on the resting calcium ions but obvious effect on the NE-induced and high potassium level-induced elevation of calcium ions. In the presence of extracellular calcium ions, Pro (50 ?mol/L) decreased the NE-induced elevation of calcium ions but showed no effect on potassium-induced elevation of calcium. Pro (100 ?mol/L) significantly decreased NE-induced and high potassium level-induced elevation of calcium ions. Conclusion Pro reduces NE-induced or high potassium level-induced elevation of calcium ions in the smooth muscle of the thoracic aorta through its effect on calcium release and/or calcium influx.

Effects of Rhynchophylla total alkaloids on experimental cerebral ischemia / 中国药理学通报

Aim To study the protective effects of Rhynchophyll a of total alkaloids ( RTA ) on cerebral ischemia/reperfusion injury and the possi ble mechanism of action. Methods The effects of RTA on decapit ated gasping model and model of middle cerebral artery ischemia 2 h/reperfusion 22 h were observed. The neurological scores, cerebral infarct volume and cerebr al water content after ischemia/reperfusion were observed in rats respectively. The activities of NOS and SOD and the content of MDA in rat's brain tissue were measured. Neuron apoptosis in ischemia penumbral area were detected by terminal depoxynucleotidyl transferase mediated dUTP-biotin nick end labeling ( TUNEL ) . Results The average gasping times in mice treated with RTA 50 , 75 mg?kg -1 was significantly prolonged. The cerebral infarct volume and cerebral water content in rats treated with RTA 40, 60 mg?kg -1 were sign ificantly decreased in ischemic rats. RTA 40, 60 mg?kg -1 increased the ac tivity of SOD ,and decreased the activity of NOS and the content of MDA in the i schemic brains of rats. The number of apoptotic neurons in ischemia penumbral ar ea of cerebral tissue of rats treated with RTA 40, 60 mg?kg -1 was signif icantly lower than that in control rats. Conclusions RTA has pr otective effect on cerebral ischemia/reperfusion injury; this may be related to inhibit the activity of NOS and lipoperoxidation, and increasing the activity of SOD and decreasing neuron apoptosis.

Calcineurin signal transduction pathway involves in cardiomyocyte hypertrophy induced by prostaglandin F_(2?) / 中国病理生理杂志

AIM:To study the role of prostaglandin F2?(PGF2?) in cardiac hypertrophy and its relation with calcineurin(CaN) signal transduction pathway in vitro.METHODS:The cultured neonatal rat cardiomyocyte was used to observe the hypertrophic effect of PGF2?,and the hypertrophic response was assayed by measuring the cell diameter,protein content and atrial natriuretic factor(ANF) mRNA expression.For mechanism studies,the intracellular free calcium concentration([Ca2+]i) in cultured cardiomyocytes was measured by using Fura-2/AM as a fluorescent indicator.ANF and CaN mRNA expressions,and the expressions of CaN and its downstream effectors,NFAT3 and GATA4 proteins were assayed by RT-PCR and Western blotting,respectively.RESULTS:In cultured cardiomyocytes,PGF2? induced profound hypertrophic morphology change and the significant increase in cell diameter,and protein content in a concentration-dependent manner compared with those in vehicle control(P

Effects of epidural infusion of different concentrations of lidocaine on the depth of anesthesia during combined general-epidural anesthesia / 中华麻醉学杂志

Objective To evaluate the effects of epidural infusion of different concentrations of lidocaine on the amount of propofol needed to induce anesthesia and the end-tidal isoflurane concentration needed to maintain BIS at 50-55 during operation. Methods Forty-five ASA Ⅰ-Ⅱ patients of both sexes (24 males, 21 females) aged 21-60 yrs, weighing 46-77 kg undergoing elective upper abdominal surgery were randomly divided into 3 groups with 15 patients in each group : group Ⅰ epidural normal saline ( NS); group Ⅱ epidural 1 % lidocaine (Lido) and group Ⅲ 2 % Lido. An epidural catheter was inserted at T9-10 into epidural space and advanced 3-4 cm cephalad. After a test dose of 3 ml, NS or 1% or 2% Lido 10 ml was injected into the epidural space. Anesthesia was induced with propofol infusion at 25 mg?min-1. Propofol infusion was stopped when the patients stopped responding to loud voice (OAAS/2) and the amount of propofol infused was recorded. Then fentanyl 2 ?g?kg-1 and vecuronium 0.15 mg?kg-1 were given i.v. . The patients were intubated and mechanically ventilated and PETC02 was maintained at 35 mm Hg. Anesthesia was maintained with isoflurane inhalation and epidural infusion of Lido or NS at 7 ml?h-1 . BIS was maintained at 50-55 during operation. Results The amount of propofol needed to induce anesthesia was 1.23?0.34 mg?kg-1 in group Ⅱ and 1.02?0.25 mg?kg-1 in group Ⅲ compared to 1.67?0.38 mg?kg-1 in control group (group Ⅰ) (P

Inhibitory effect and mechanism of cobra venom metalloproteinase atrase A on platelet aggregation / 中国药理学通报

Aim To investigate the effect and mechanism of cobra venom metalloproteinase atrase A on inhibiting platelet aggregation.Methods Platelet aggregation induced by collagen,ADP,PAF,AA,ristocetin and thrombin,respectively,was measured turbimetrically after platelet incubated with atrase A.Western blot was used to detect the effect of atrase A on cleavage of platelet membrane glycoprotein and von Willebrand Factor.Results Atrase A significantly inhibited platelet aggregation induced by ristocetin and thrombin in a dose-and time-dependent manner.Meanwhile,atrase A just showed slight inhibitory effect on platelet aggregation induced by PAF,AA,collagen,and ADP after incubated with PRP for 5 min.After incubation time was prolonged to 30 min,significant inhibition was shown on platelet aggregation.Western blot revealed that atrase A cleaved platelet membrane glycoprotein GPIb.Conclusions Cobra venom metalloproteinase atrase A significantly inhibits platelet aggregation induced by ristocetin and thrombin due to the cleavage of platelet membrane glycoprotein Ib.And atrase A also has inhibitory effect on platelet aggregation induced by ADP,PAF,AA,and collagen.