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Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.
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Objective:To analyze the compliance with enhanced recovery after surgery (ERAS) protocol in geriatric patients with fresh fracture.Methods:A retrospective study was conducted on the data of the patients with fresh extremity fracture which had been included in the ERAS perioperative protocol database during May 2019 and January 2022 at Department of Orthopaedic Trauma, Beijing Jishuitan Hospital. The patients ≥65 years were selected as a study group which was matched by a control group of the patients < 65 years in sex, fracture type and date frame of hospitalization at a ratio of 1∶1. The 2 groups were compared in the compliance with the 14 ERAS core perioperative elements.Results:The study group and the control group each included 66 patients who were matched in sex and fracture type. 62.1% (41/66) of the patients in the study group had combined diseases, significantly more than that [16.7% (11/66)] in the control group( P<0.001). Altogether, the compliance with the 14 ERAS core perioperative elements was 78.6 (71.4, 85.7) % in both groups, showing no significant difference between them ( P>0.05). Respectively, the compliance with the postoperative oral intake in the study group (80.3%, 53/66) was significantly lower than that in the control group (92.4%, 61/66) ( P<0.05); the compliance with the other 13 elements showed no statistically significant difference between the 2 groups ( P>0.05). Conclusion:The ERAS perioperative protocol can be carried out smoothly in geriatric patients with fresh fracture whose compliance may be comparable to that of the none-elderly patients.
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[Abstract] Objective To elucidate the important role of Nogo-A in climacteric neurodegeneration such as memory impairment by observing memory function and the expression of Nogo-A in hippocampus and striatum of rats under low estrogen condition. Methods Fouthy-five female SD rats were divided into sham operation group, ovariectomized group and ovariectomized estrogen treatment group with 15 rats in each group. Medication was given 2 weeks after ovariectomized. Estrogen treatment group was subcutaneously injected in groin with estrogen [25 μg/ (kg.d)] dissolved in sterile sesame oil. The sham operation group and the ovariectomized group were given the same amount of aseptic sesame oil. Samples were collected after 6 weeks of drug treatment. The difference of memory function of rats in three groups was observed by conditioned fear training experiment, and the expression of Nogo-A in hippocampus and striatum was observed by immunohistochemistry and Western blotting. Results Compared with the sham and estrogen treatment group, memory function in ovariectomized group decreased significantly and the number of Nogo-A positive neurons in hippocampus and striatum of ovariectomized rats was significantly higher than that of sham operation group (P 0. 05). The result of immunoblotting was consistent with the above-mentioned immunohistochemical result. Conclusion The increased expression of Nogo-A in hippocampus and striatum under low estrogen condition may be one of the key reasons for memory impairment in climacteric women.
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In order to better control the quality of Flos Puerariae(FP),qualitative and quantitative analyses were initially performed by using chemical fingerprint and chemometrics methods in this study.First,the fingerprint of FP was developed by HPLC and the chemical markers were screened out by similarity analysis(SA),hierarchical clustering analysis(HCA),principal components analysis(PCA),and orthogonal partial least squares discriminant analysis(OPLS-DA).Next,the chemical constituents in FP were profiled and identified by HPLC coupled to Fourier transform ion cyclotron resonance mass spectrometry(HPLC-FT-ICR MS).Then,the characteristic constituents in FP were quantitatively analyzed by HPLC.As a result,31 common peaks were assigned in the fingerprint and 6 of them were considered as qualitative markers.A total of 35 chemical constituents were detected by HPLC-FT-ICR MS and 16 of them were unambiguously identified by comparing retention time,UV absorption wavelength,accurate mass,and MS/MS data with those of reference standards.Subsequently,the contents of glycitin,genistin,tectoridin,glycitein,genistein,and tectorigenin in 13 batches of FP were detected,ranging from 0.4438 to 11.06 mg/g,0.955 to 1.726 mg/g,9.81 to 57.22 mg/g,3.349 to 41.60 mg/g,0.3576 to 0.989 mg/g,and 2.126 to 9.99 mg/g,respectively.In conclusion,fingerprint analysis in combination with chemometrics methods could discover chemical markers for improving the quality control standard of FP.It is expected that the strategy applied in this study will be valuable for further quality control of other traditional Chinese medicines.
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Objective:To explore the characteristics and clinical values of preoperative imaging signs and intraoperative stress test in the surgery of the Weber type B fracture without medial malleolar fracture.Methods:The data of 52 patients were reviewed who had been treated at Orthopaedic Trauma Department, Beijing Jishuitan Hospital for Weber type B ankle fracture without medial malleolar fracture from January 2018 to December 2021.They were assigned into 2 groups depending on their results of intraoperative stress test. In the positive group of 21 cases showing a positive intraoperative stress test, there were 19 males and 2 females with an age of (34.4±10.2) years; in the negative group of 31 cases showing a negative intra operative stress test, there were 22 males and 9 females with an age of (39.5±14.8) years. The 2 groups were compared in terms of the medial clear space, tibiofibular clear space and vertical length of the fibular fracture on the preoperative X-ray film, as well as the relative size of the posterior malleolar fracture fragment on the preoperative CT. The imaging characteristics of intraoperative stress tests were also observed.Results:There was no significant difference between the 2 groups in the preoperative general data, showing comparability between groups ( P>0.05). The medial clear space (7.2±2.5) mm and the vertical length of the fibular fracture [49.2 (33.7, 58.7) mm] in the positive group were significantly larger than those in the negative group [(4.5±1.7) mm and 29.6 (24.7, 36.0) mm] ( P<0.05). There was no significant difference between the 2 groups in the lower tibiofibular space [(6.0±1.9) mm versus (5.2 ± 1.4) mm] or in the relative size of posterior malleolar fracture measured by CT [15.8% (6.9%, 19.1%) versus 12.7% (0%, 18.9%)] ( P>0.05). The intraoperative stress test imaging data of a total of 22 cases were collected from the 2 groups (11 cases from each of the 2 groups). During the stress test, only the medial clear space was widened with no widening of the inferior tibiofibular space was found in 7 cases (5 cases in the positive group and 2 cases in the negative group). Conclusions:A routine stress test is recommended for Weber B ankle fracture without medial malleolus fracture, because instability sometimes exists after fibular fixation. Patients with a wider medial clear space and a longer fibular fracture line on X-ray after injury are more likely to be afflicted by instability after fibular fixation. In the patients with a widened medial clear space but without a widened inferior tibiofibular clear space during an intraoperative stress test, it calls for further study whether it is necessary to fix the inferior tibiofibular joint.
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Isoflavones are widely consumed by people around the world in the form of soy products, dietary supplements and drugs. Many isoflavones or related crude extracts have been reported to exert pain-relief activities, but the mechanism remains unclear. Voltage-gated sodium channels (VGSCs) play important roles in excitability of pain sensing neurons and many of them are important nociceptors. Here, we report that several isoflavones including 3'-methoxydaidzein (3MOD), genistein (GEN) and daidzein (DAI) show abilities to block VGSCs and thus to attenuate chemicals and heat induced acute pain or chronic constriction injury (CCI) induced pain hypersensitivity in mice. Especially, 3MOD shows strong analgesic potential without inducing addiction through inhibiting subtypes Na1.7, Na1.8 and Na1.3 with the IC of 181 ± 14, 397 ± 26, and 505 ± 46 nmol·L, respectively, providing a promising compound or parent structure for the treatment of pain pathologies. This study reveals a pain-alleviating mechanism of dietary isoflavones and may provide a convenient avenue to alleviate pain.
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Animais , Humanos , Masculino , Camundongos , Analgésicos , Química , Isoflavonas , Química , Camundongos Endogâmicos C57BL , Dor , Tratamento Farmacológico , Genética , Metabolismo , Bloqueadores do Canal de Sódio Disparado por Voltagem , Canais de Sódio Disparados por Voltagem , Genética , MetabolismoRESUMO
To investigate the protective effects of ginkgo diterpene lactone meglumine injection (GDLMI) on cerebral focal ischemia reperfusion injury induced by middle cerebral artery occlusion (MCAO) in rats, and explore its possible mechanism. One hundred and forty male SD rats were randomly divided into sham operation group, model group, ginkgo biloba extract injection (Ginaton, 1.0 mL•kg⁻¹) group, nimodipine (0.4 mg•kg⁻¹) group, and GDLMI (5.2, 2.6, 1.3 mg•kg⁻¹) groups; All of rats received corresponding drugs by tail vein injection 4 days before operation (normal saline in model group and sham operation group). Except the sham operation group, the cerebral ischemic stroke model was established by MCAO method in right brain of the other rats. After 3 h of ischemia, all the animals received intravenous administration again. The neurobehavioral scores of rats after ischemia-reperfusion were evaluated and the infarct rate of brain tissue was observed by TTC staining. The super oxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and lactic acid (LA) contents in brain tissue homogenate and the concentration of Ca2+, glutamate (Glu) and aspartate (Asp), creatine phosphate kinase (CK-BB) and lactate dehydrogenase (LDH) content changes in cerebrospinal fluid were measured. As compared with the sham operation group, the cerebral infarction rate was increased significantly in the model group; the content of MDA and LA in the homogenate of brain tissue was increased, and the content of GSH and SOD was decreased; in cerebrospinal fluid, Ca2+ concentration was decreased, and the content of Glu and Asp, CK-BB and LDH increased significantly. As compared with the model group, the high and medium dose GDLMI groups can significantly reduce the cerebral infarction rate and improve the symptoms of neurological impairment; increase SOD and GSH activity, reduce MDA and LA content in serum; increase Ca2+ concentration in cerebrospinal fluid and decrease the content of neurotransmitter Glu and Asp as well as CK-BB and LDH. GDLMI could obviously improve neurologic impairment in model rats, and the mechanism may be related to recovering the blood brain barrier, scavenging free radicals, decreasing free Ca2+ inflow into the cells and the content of excitatory amino acid in cerebrospinal fluid to improve its protective effect on cerebral ischemia.
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<p><b>OBJECTIVE</b>To investigate the effects of ischemic postconditioning on the expression of HO-1 in the liver graft ischemia and reperfusion injury in rats.</p><p><b>METHODS</b>Fifty-six male SD rats were randomly divided into four groups: sham-operation group (sham) (n = 8), ischemia and reperfusion group (I/R)(n = 16), ischemic postconditioning group (IPo) (n = 16) and inhibitor of HO-1 group (ZnPP) (n = 16). Donor livers were preserved in 0 - 4 degrees C normal saline, and the period of cold preservation and anhepatic phase were 90 min and 15 min. At 6 h after portal vein reperfusion, blood samples were obtained from the abdominal aorta to determine the level of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), simultaneously liver tissues were taken to determine the level of malondialdehyde (MDA), superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) mRNA. The changes of liver tissues were observed by HE staining and electron microscope.</p><p><b>RESULTS</b>SOD activity was significantly lower whereas MDA content was significantly higher in I/R group than that in Sham group (P < 0.05). The expression of HO-1 in I/R group was higher than that in Sham group (P < 0.05). MDA content was significantly lower whereas SOD activity was significantly higher in IPO group than that in I/R group (P < 0.05), and the expression of HO-1 in IPO group was significantly stronger than that in I/R group (P < 0.05). SOD activity and the expression of HO-1 were significantly lower whereas MDA content was significantly higher in ZnPP group than that in I/R group (P < 0.05). The changes of liver tissues also proved the previous results.</p><p><b>CONCLUSIONS</b>Ischemic postconditioning attenuates liver graft injury induced by I/R in rats. The mechanism might be related with the induction of HO-1 and enhancement of liver graft antioxidation.</p>
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Animais , Masculino , Ratos , Modelos Animais de Doenças , Heme Oxigenase (Desciclizante) , Metabolismo , Fígado , Metabolismo , Patologia , Transplante de Fígado , Distribuição Aleatória , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Metabolismo , PatologiaRESUMO
<p><b>BACKGROUND</b>The neuroprotective effect of the cyclooxygenase (COX) inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil (FA, COX inhibitor) and its therapeutic time window in a model of transient middle cerebral artery occlusion (MCAO) in rats.</p><p><b>METHODS</b>Forty-eight male SD rats were randomly assigned into six groups (n = 8 in each group); three FA groups, vehicle, sham and ischemia/reperfusion (I/R) groups. Three doses of FA (5, 10 or 20 mg/kg, intravenous infusion) were administered just after cerebral ischemia/reperfusion (I/R). The degree of neurological outcome was measured by the neurologic deficit score (NDS) at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage (MBIVP) was determined with 2, 3, 5-triphenyltetrazolium chloride (TTC) staining at 72 hours after I/R. In three other groups (n = 8 in each group), the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R.</p><p><b>RESULTS</b>The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12 - 24 hours after ischemia reperfusion.</p><p><b>CONCLUSION</b>COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12 - 24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.</p>
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Animais , Masculino , Ratos , Inibidores de Ciclo-Oxigenase , Farmacologia , Modelos Animais de Doenças , Flurbiprofeno , Farmacologia , Infusões Intravenosas , Ataque Isquêmico Transitório , Tratamento Farmacológico , Patologia , Distribuição Aleatória , Ratos Sprague-Dawley , Fatores de TempoRESUMO
<p><b>OBJECTIVE</b>To establish ELISAs based on rLipL32/1-LipL21-OmpL1/2 fusion antigen of Leptospira interrogans for detecting specific IgG and IgM in serum of patients with leptospirosis.</p><p><b>METHODS</b>Microscope agglutination test(MAT) was performed to detect serum specimens from leptospirosis patients and to determine titers of rabbbit antiserum agaist rLipL32/1-LipL21-OmpL1/2 to reference standard strains of L. interrogans. By using rLipL32/1-LipL21-OmpL1/2, rLipL32/1, rLipL21 and rOmpL1/2 as the coated antigens, ELISAs for detecting specific serum IgM and IgG were established. The established ELISAs were applied to MAT-positive serum specimens from 107 patients with leptospirosis.</p><p><b>RESULT</b>The results of MAT confirmed that 66% (71/107) of the patients were infected with L.interrogans serogroup Icterohaemorrhagiae, and the rLipL32/1-LipL21-OmpL1/2 antiserum were able to agglutinate all 15 reference standard L.interrogans strains with 1 : 20approximate, equals1 : 160 titers. The positive rates of ELISAs using rLipL32/1-LipL21-OmpL1/2, rLipL32/1, rLipL21 or rOmpL1/2 as the antigen were 89.7%, 75.7%, 85.1% and 79.4% for detecting IgM, respectively, while 99.1%, 99.1%, 94.4% and 86.0% for detecting IgG, respectively. The positive detection rate of rLipL32/1-LipL21-OmpL1/2-IgM-ELISA was higher than those of the other three IgM detection ELISAs (P<0.05). The positive detection rate of rLipL32/1-LipL21-OmpL1/2-IgG-ELISA was higher than that of rOmpL1/2-IgG-ELISA (P<0.05), while there was no significant differnce with that of rLipL21-IgG-ELISA and rLipL32/1-IgG-ELISA (P>0.05).</p><p><b>CONCLUSION</b>The ELISAs using rLipL32/1-LipL21-OmpL1/2 as the antigen can be applied as a sensitive,specific and universal serological method for diagnosis of leptospirosis.rLipL32/1-LipL21-OmpL1/2-IgM-ELISA shows a definite value for early diagnosis of leptospirosis compared with the other ELISAs used in this study.</p>
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Animais , Humanos , Coelhos , Testes de Aglutinação , Anticorpos Antibacterianos , Sangue , Antígenos de Bactérias , Genética , Metabolismo , Proteínas da Membrana Bacteriana Externa , Genética , Metabolismo , Ensaio de Imunoadsorção Enzimática , Escherichia coli , Genética , Metabolismo , Imunoglobulina G , Sangue , Imunoglobulina M , Sangue , Leptospira interrogans , Genética , Alergia e Imunologia , Leptospirose , Diagnóstico , Alergia e Imunologia , Lipoproteínas , Genética , Metabolismo , Proteínas Recombinantes de Fusão , Genética , Alergia e Imunologia , Metabolismo , Sensibilidade e Especificidade , Testes Sorológicos , MétodosRESUMO
<p><b>OBJECTIVE</b>To investigate the effect of puerarin on the neural function and the histopathological changes after ischemic spinal cord injury in rabbits.</p><p><b>METHODS</b>Thirty male New Zealand white rabbits were randomly divided into three groups as follows: puerarin group (n=10) receiving intravenous infusion of 30 mg/kg puerarin for 10 minutes, control group (n=10) receiving intravenous infusion of the same volume of normal saline as puerarin for 10 minutes, and sham operation group (n=10) undergoing only the surgical exposure of the abdominal aorta. Temporary spinal cord ischemia was induced by infrarenal aortic occlusion for 20 minutes and followed by reperfusion. The neural status was scored with the Tarlov criteria at 8, 12, 24 and 48 hours after reperfusion. All the animals were killed at 48 hours after reperfusion and the spinal cords (L5) were removed immediately for histopathological study.</p><p><b>RESULTS</b>The neural function scores at 8, 12, 24 and 48 hours after reperfusion were higher in the puerarin group and sham operation group than those in the control group (P<0.05). More normal motor neurons in the anterior horn of spinal cord were present in the puerarin group and sham operation group than those in the control group (P<0.01). There was a strong correlation between the final neural function scores and the number of normal motor neurons in the anterior horn of spinal cord (r=0.839, P<0.01).</p><p><b>CONCLUSIONS</b>Puerarin can significantly ameliorate the neural function and the histopathological damages after transient spinal cord ischemia in rabbits.</p>