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Objective:To analyze the improvement effect of monk fruit on diabetic nephropathy(DN)by network pharmacology,and to elucidate its possible related mechanism.Methods:The Traditional Chinese Medicine Systems Pharmacology(TCMSP)Database was used to detect the active ingredients and their targets of monk fruit;the DN target genes were screened out by DisGeNET Database and Genecards Database;the key targets of monk fruit against DN were obtained by comparing the monk fruit with DN targets;protein-protein interaction(PPI)network diagram was constructed by STRING Database and Cytoscape software;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed by Cytoscape software.Molecular docking technology was used to predict the binding abilities of the core targets and the main active ingredients of monk fruit.Results:The TCMSP Database combined with the selection criteria was used to screen out a total of five active ingredients of monk fruit(ZINC03860434,Perlolyrine,beta-sitosterol,Kaempferol,and Flazin)as well as 85 targets represented by serine/threonine protein kinase 1(AKT1),transcription factor RELA,c-Jun N-terminal kinase(JUN),and tumor necrosis factor(TNF).Among them,Kaempferol contained the most targets.Among the 85 targets,34 were associated with DN.The GO functional enrichment analysis mainly included biological process(BP)such as oxidative stress,regulation of inflammation and apoptosis,and cell signaling transduction.The KEGG enrichment analysis included advanced glycosylation end product(AGE)-receptor of AGE(AGE-RAGE)signaling pathway,TNF signaling pathway,and C-type lectin receptor signaling pathway.The results molecular docking technology of the main active ingredients of monk fruit and DN target proteins showed that 5 kinds of molecular docking engergy were-8.00--5.00 kJ·mol-1.Conclusion:Kaempferol is the most effective active ingredient in the monk fruit for the treatment of DN,and its mechanism is mainly related to anti-inflammatory.
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ObjectiveBased on spatial metabolomics technology combined with pharmacological indexes， to analyze the mechanism of Fritillariae Cirrhosae Bulbus（FCB） powder in improving bleomycin-induced pulmonary fibrosis in rats. MethodSixty SD rats were randomly divided into five groups， including the blank group， the model group， and high， medium， low dosage groups of FCB. Except for the blank group， rats in all other groups were injected with bleomycin by tracheal injection to establish a pulmonary fibrosis model. Postoperatively， the high， medium and low dosage groups of FCB were administered aqueous solutions of FCB powder at doses of 0.36， 0.18， 0.09 g·kg-1， respectively， continuously for 28 d. The blank and model groups were given an equal volume of distilled water by gavage. After the last administration， lung tissues and blood samples were collected， the pathological conditions of rat lung tissues were comprehensively evaluated by hematoxylin-eosin（HE） and Masson staining， and aerodynamic assisted desorption electrospray ionization mass spectrometry imaging（AFADESI-MSI） was used for MSI of rat lung tissues from different experimental groups. Spatial metabolomics analysis was conducted on the fibrotic areas of lung tissues in the model group and the high dosage group of FCB based on HE staining images. Differential metabolites between groups were screened by orthogonal partial least squares-discriminant analysis（OPLS-DA）， with variable importance in the projection（VIP） values>1， t-test P<0.05， and fold change analysis. Metabolic pathway analysis of the identified differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG）. Protein expression levels of nuclear transcription factor-κB p65（NF-κB p65） and heme oxygenase-1（HO-1） in rat lung tissues were detected by Western blot. Biochemical assessments of superoxide dismutase（SOD）， malondialdehyde（MDA） and glutathione（GSH） levels in rat lung tissues were conducted. Serum levels of interleukin（IL）-1β， IL-6， nuclear factor erythroid 2 related factor 2（Nrf2）， and tumor necrosis factor-α（TNF-α） were measured by enzyme linked immunosorbent assay（ELISA）， and some of the screened signaling pathways with strong correlation were verified. ResultThe results of MSI experiment showed that after 28 d of the administration of FCB powder to rats with pulmonary fibrosis， the content of L-arginine in the fibrotic regions of lung tissues was significantly different from that of rats in the model group， and the content of phosphatidylcholine was lower than that in the fibrotic region of lung tissues of rats in the model group. Western blot results confirmed that， in comparison to the model group， oral administration of FCB powder for 28 d could inhibit the elevated expression of NF-κB p65 protein in the lung tissues of rats with pulmonary fibrosis. Furthermore， high dose of FCB powder was able to significantly inhibit the expression of HO-1 after oral administration （P<0.05）. The cytokine detection results indicated that the concentrations of IL-1β， IL-6 and TNF-α in the serum of rats from the high， medium， low dosage groups of FCB were reduced by comparing with the model group， and the high dose of Chuanbeimu powder administered by gavage could significantly inhibit the trend of decreased SOD， GSH， Nrf2 contents and increased MDA content induced by bleomycin. ConclusionOral administration of FCB powder has the potential to partially ameliorate bleomycin-induced pulmonary fibrosis in rats， and its mechanism may be related to the regulation of pathways associated with inflammation（NF-κB p65） and oxidative stress（Nrf2/HO-1）.
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Objective To evaluate the effects of ultrasound-guided paravertebral nerve block(PVNB)and local infiltration anes-thesia on postoperative inflammation level and recovery quality of patients after robot-assisted radical nephrectomy.Methods A total of 100 patients who underwent elective robot-assisted laparoscopic radical nephrectomy in General Hospital of Central Theater Command from January 2022 to August 2022 were selected prospectively.They were randomly divided into observation group and control group by random number table method,with 50 cases in each group.The observation group chose general anesthesia combined with PVNB,while the control group chose general anesthesia combined with incision local infiltration anesthesia.All patients were connected with patient-controlled intravenous analgesia(PCIA)after operation.The pain visual analogue scale(VAS)of rest and cough,the systemic immune inflammatory index(SII),interleukin-6(IL-6),and the QoR-15 scores of the patients after operation in the two groups were recor-ded.The dosage of remifentanil,the times of effective compression of analgesia pump and remedial analgesia were recorded in the two groups.Adverse reactions and related complications were recorded.Results Compared with the control group,the pain VAS of rest and cough in the observation group were lower on first and second day after operation(P<0.05).SII and IL-6 were lower on the first and third day after operation(P<0.05).The QoR-15 scores on the first,second,and fifth day after operation were higher(P<0.05).The dosage of remifentanil was less during operation(P<0.01).The effective pressing times of intravenous analgesia pump were less af-ter operation(P<0.05).Lower incidence of remedial analgesia and adverse effects(P>0.05).Conclusion Compared with local in-filtration anesthesia,PVNB can provide better intraoperative and postoperative analgesia effect,reduce the early postoperative inflammato-ry reaction and accelerate the early recovery of patients for robot-assisted radical nephrectomy.
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OBJECTIVE：To study the effects of chrysophanol on the activa tion of microglia and the expression of inflammatory factors in cerebral ischemia model rats. METHODS ：SD rats were randomly divided into sham operation group ， model group and chrysophanol high ，medium，low dose groups [7.88，3.94，1.97 mg/（kg·d）]，with 20 rats in each group （the number was complemented in cases of death or unsuccessful modeling during modeling process ）. Except for sham operation group ， middle cerebral artery occlusion model was established in other groups by improved thread method. After 2 hours of ischemia ， sham operation group and model group were intraperitoneally injected with 1 mL normal saline ，and each administration group was intraperitoneally injected with 1 mL corresponding drug ，once a day ，for 7 consecutive days. After last medication ，the score of neurological impairment was recorded ；cerebral infarction of rats was observed by TTC staining ，and the percentage of cerebral infarction area was calculated. The expression of Iba- 1 positive cells in ischemic penumbra of rats was observed by immunofluorescence staining. The expression of Notch- 1，TNF-α and ICAM-1 in the ischemic penumbra of rats were detected by Western blotting assay. RESULTS ：In sham operation group ，there was no infarction area in the brain tissue ，and the Iba- 1 positive cells in the ischemic penumbra were few and branched. Compared with sham operation group ，the infarction area of cerebral tissue in rats was obvious in model group ； the 052）number of Iba- 1 positive cells in ischemic penumbra were 〔ZQ2017003〕） increased significantly ，and they were in amoeba or round shape；the neurological impairment score ，the percentage of cerebral infarction area ， relative expression of Notch- 1， TNF-α and ICAM-1 protein in ischemic penumbra were increased significantly （P＜0.05）. Compared with m odel rats ，the infarction area of cerebral tissue in each dose group of chrysophanol was reduced to different extent ；the number of Iba- 1 positive cells in ischemic penumbra was decreased ；neurological impairment score ，the percentage of cerebral infarction area ，relative expression of Notch- 1，TNF-α and ICAM-1 protein were significantly decreased （P＜0.05 or P＜0.01）. CONCLUSIONS ：Chrysophanol has a certain protective effect on the brain tissue of cerebral ischemia model rats ，and can relieve the nerve injury. Its mechanism may be associated with inhibiting the activation of microglia and expression of inflammatory factors mediated by Notch pathway.
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OBJECTIVE： To observe the effects of nicorandil on vascular endothelial function and angina pectoris recurrence in patients with unstable angina pectoris after percutaneous coronary intervention （PCI）. METHODS： Totally 195 patients with unstable angina pectoris were collected from Sichuan Provincial People’s Hospital during Jan. 2016-Mar. 2018， and then divided into control group （97 cases） and observation group （98 cases） according to random number table. Both groups received PCI， and then given basic treatment as Enoxaparin sodium injection， Isosorbide mononitrate sustained-release tablets， Aspirin enteric-coated tablets， Clopidogrel sulfate tablets and Atorvastatin calcium tablets after PCI. Observation group additional received Nicorandil tablet 5 mg， tid， on the basis of control group. Both groups were treated for 6 months. The levels of vascular endothelial function related indexes （FMD， ET-1， NO）， myocardial injury markers （cTnⅠ， CK-MB） and inflammatory factors （hs-CRP） were observed before and after PCI. The recurrent angina pectoris， the occurrence of MACE and ADR were recorded. RESULTS： 6 patients of control group and 4 patients of observation group withdrew from the study. One day before operation， there was no significant difference in the levels of vascular endothelial function， myocardial injury markers or inflammatory factors between 2 groups （P＞0.05）. One day after operation， the levels of FMD and NO in both groups decreased significantly， while the levels of ET-1， cTnⅠ and CK-MB increased significantly （P＜0.05）. The levels of FMD and NO were increased significantly in the 1st and 6th months after surgery， and the observation group was significantly higher than the control group； the levels of ET-1， cTnⅠ， CK-MB and hs-CRP were decreased significantly， and the observation group was significantly lower than the control group （P＜0.05）. The incidence and times of recurrent angina pectoris， duration， the proportion of grade Ⅲ angina pectoris and total incidence of MACE in observation group were significantly lower， less or shorter than control group （P＜0.05）. There was no statistical significance in total incidence of ADR between 2 groups （P＞0.05）. CONCLUSIONS： Additional use of nicorandil can improve vascular endothelial function， relieve the myocardial injury and inflammatory response， reduce the occurrence of recurrent angina pectoris and MACE after PCI and doesn’t influence the safety of routine treatment.
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Objective The expressions of inflammatory factors and brain edema after traumatic brain injury (TBI) are the main factors for deterioration of the condition.TBI after drunkenness is even more difficult to be managed than simple TBI.This study was to discuss the effects of drunkenness on the inflammatory factors TNF-o and IL-6 and the aquaporin-4 (AQP-4) protein in rats after TBI.Methods Forty-eight male adult SD rats were randomly divided into a TBI and an ethanol (ETH) pretreatment group.TBI was induced using the Feeney's method after intraperitoneal injection of 3％ chloral hydrate at 30 mg/kg (the TBI group) or following gavage of ETH (the ETH group).At 1,3 and 5 days after modeling,modified neurological function scores (mNSS) were obtained,the expressions of TNF-α,IL-6 and AQP-4 protein determined by Western blot,and the levels of TNF-α.IL-6 and AOP-4 mRNA measured by RT-PCR at 6,24 and 72 hours.Results Compared with the TBI group,the ETH group showed significantly decreased mNSS at 1 day (9.00±0.63 vs 7.17±1.72,P＜0.05),3 days (7.00±1.10 vs 4.83±1.47,P＜0.05) and 5 days after modeling (5.50±1.05 vs 3.83± 0.75,P＜ 0.05),but remarkably up-regulated expressions of TNF-α (0.068± 0.008 vs 0.257 ± 0.008,P＜ 0.01),IL-6 (0.102 ±0.013 vs 0.320±0.016,P＜0.01) and APQ4 (0.054±0.007 vs 0.212±0.015,P＜0.01) at 6 hours,as well as at 24 and 72 hours (P＜0.01).Conclusion Drunkenness may increase the expressions of inflammatory factors and brain edema after traumatic brain injury and consequently aggravate secondary brain injury.
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OBJECTIVE:To investigate the effects and mechanism of total flavonoids from Armeniaca mume on depression in chronic stress depression model rats. METHODS:60 rats were randomly divided into normal saline group,model group,fluox-etine group(positive control,20 mg/kg)and total flavonoids from A. mume low-dose,medium-dose,high-dose groups(80,160, 240 mg/kg), 10 in each group. Except for normal saline group, the other groups adopted chronic unpredictable mild stress (CUMS)+solitary feeding condition to induce depression model. These groups were intragastrically administered,once a day,for 28 d. Changes of body mass and food intake,degree of preference for sugar were observed;forced swimming test and tail suspen-sion test were used to determine the time that rats did not move;open field test was used to determine the changes of residence time in central square,horizontal crossing lattice,standing times,modification times;tumor necrosis factor α(TNF-α),cortisol, interleukin 6 (IL-6),serotonin (5-HT) levels in serum after 24 h of last administration were determined. RESULTS:Compared with normal saline group,growth of body mass,food intake and sugar preference percentage in model group were decreased;the time that rats did not move was prolonged in forced swimming test and tail suspension test;residence time in central square was prolonged,while horizontal crossing lattice,standing times and modification times were decreased in open field test;serum levels of TNF-α,cortisol were increased,while IL-6,5-HT were decreased,with statistical significances (P<0.05 or P<0.01). Com-pared with model group,except that there were no obvious improvement in sugar preference percentage,the time that rats did not move in forced swimming test,modification times in open field test in total flavonoids from A. mume low-dose group and IL-6, 5-HT levels in serum in total flavonoids from A. mume low-dose,medium-dose groups,the above-mentioned indexes were obvious-ly improved in other groups (P<0.05 or P<0.01). CONCLUSIONS:Total flavonoids from A. mume can obviously improve the CUMS-induced depression in rats,and the mechanism may be related to inhibiting inflammation response,adjusting the hypothala-mus-pituitary-adrenal axis functions.
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OBJECTIVE:To explore the effects of xingnaojing combined with naloxone on related indexes of patients with he-patic encephalopathy. METHODS:In retrospective analysis,76 patients with hepatic encephalopathy were divided into control group(40 cases)and observation group(36 cases)according to drug use. Based on routine treatment,control group was additional-ly given Naloxone injection 1 mg added into 10% Glucose solution 100 mL intravenously twice a day. Observation group was addi-tionally given Xingnaojing injection 20 mL added into 0.9% Sodium chloride injection 250 mL intravenously once a day on the ba-sis of control group. Treatment courses of 2 groups lasted for 2 weeks. HDS score,MMSE score,the levels of blood ammonia,β-endorphin,CRP,IL-6 and TNF-α,the occurrence of ADR were observed in 2 groups before and after treatment. RESULTS:Af-ter treatment,HDS score and MMSE score of 2 groups were significantly higher than before treatment,and the observation group was significantly higher than the control group;the levels of blood ammonia,β-endorphin,IL-6,CRP and TNF-α in 2 groups were significantly lower than before treatment,and the observation group was significantly lower than the control group,with statis-tical significance(P0.05). There was no statistical significantly in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Based on routine treatment,Xingnaojing combined with naloxone can significantly improve cognitive function for patients with hepatic en-cephalopathy and reduce peripheral blood neurotoxin and inflammatory factor,moreover,do not increase the incidence of ADR.
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Objective @#To compare the inflammatory reaction of peritoneal macrophage after Pg-LPS stimulated in healthy rabbit and hyperlipidemia rabbit. @*Methods @#12 New Zealand rabbits were randomly divided into 2 groups with 6 rabbits in each group, and normal diet and high-fat diet were fed to them respectively. The hyperlipidemia model was set up after 6 weeks. The peritoneal macrophage in normal and hyperlipidemia group were isolated and cultured, and then the cells in both groups were respectively divided into 3 groups: control, 1 μg/mL Pg-LPS, and 1 μg/mL E.coli-LPS. After 24 h treatment, the expressions of C-reaction protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6) , interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were detected by realtime PCR. @*Results @#The levels of CRP, IL-1β, IL-6, IL-8, and TNF-α were higher in hyperlipidemia control group than normal control group. The expressions of inflammatory substances were increased after stimulated by Pg-LPS, and statistically higher in hyperlipidemia rabbit group than normal group (P < 0.05). @*Conclusion@#Pg-LPS can enhance the mRNA expressions of inflammation related factors in peritoneal macrophage in hyperlipidemia rabbit.
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Objective To investigate the effect of clopidogrel on platelet function and inflammation factor in treatment of severe carotid artery stenosis after stent-assisted angioplasty.Methods Patients (120 cases) with severe carotid artery stenosis after stent-assisted angioplasty were chosen and divided into two groups,the control group were given atorvastatin combined with aspirin,and the observation group were given atorvastatin combined with chlorine.The serum coagulants DD level,FIB level,inflammation factor P-chosen element level and restenosis event incidence of two groups were observed.Results D-double polymer of two groups had no significant difference;After surgery,the D-double polymer and FIB level of two groups were all higher (P ＜ 0.05).After surgery for 24 h,the D-double polymer and FIB level of observation group were higher,after 3 months of surgery,the D-double polymer and FIB level had no significant differences compared with before surgery,which were all in normal level.After 24 h,1 month,3 months of surgery,the D-double polymer and FIB level of observation group were all lower than control group (P ＜ 0.05).Before treatment,the P-chosen selectin of two groups had no significant differences,which were all decreased after surgery,and the observation group was lower than control group (P ＜ 0.05);The restenosis event of observation group was lower than control group (P ＜ 0.05).Conclusion Clopidogrel could control the platelet aggregation of severe carotid stenosis after surgery to prevent the thrombogenesis and decrease the restriction incidence,while control the inflammation factor expression to prevent the atherosclerosis.
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Objective To investigate the effect of clopidogrel on platelet function and inflammation factor in treatment of severe carotid artery stenosis after stent-assisted angioplasty.Methods Patients (120 cases) with severe carotid artery stenosis after stent-assisted angioplasty were chosen and divided into two groups,the control group were given atorvastatin combined with aspirin,and the observation group were given atorvastatin combined with chlorine.The serum coagulants DD level,FIB level,inflammation factor P-chosen element level and restenosis event incidence of two groups were observed.Results D-double polymer of two groups had no significant difference;After surgery,the D-double polymer and FIB level of two groups were all higher (P ＜ 0.05).After surgery for 24 h,the D-double polymer and FIB level of observation group were higher,after 3 months of surgery,the D-double polymer and FIB level had no significant differences compared with before surgery,which were all in normal level.After 24 h,1 month,3 months of surgery,the D-double polymer and FIB level of observation group were all lower than control group (P ＜ 0.05).Before treatment,the P-chosen selectin of two groups had no significant differences,which were all decreased after surgery,and the observation group was lower than control group (P ＜ 0.05);The restenosis event of observation group was lower than control group (P ＜ 0.05).Conclusion Clopidogrel could control the platelet aggregation of severe carotid stenosis after surgery to prevent the thrombogenesis and decrease the restriction incidence,while control the inflammation factor expression to prevent the atherosclerosis.
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Objective To study the effect and mechanism of Water extract from Jiangtang Decoction (WEJTD) on diabetes mellitus and diabetic nephropathy (DN) in spontaneous type 2 diabetes mellitus model KK-Ay mice.Methods Totally 50 KK-Ay mice were randomly divided into five groups:model group,metformin (positive drug,250 mg/kg) group,WEJTD low,medium and high dose (2,4,and 8 g/kg) group,with 10 C57BL/6J mice as normal group.The relative drugs were ig administered once a day for 12 weeks,and mice in control group and model group were perfused with distilled water of equal volume.After 12 weeks' oral administration,mice were put into metabolism cages,and the food-intake,water-intake and urine volume were calculated and collected.Blood were collected to detect the concentration of IL-6,ICAM-1 and TNF-α.Then mice were executed,and HE staining and PASM staining were used to check the effect of WEJTD on kidney.Western blotting and qRT-PCR were used to detect the concentration of PI3K,Akt,NF-κB,IL-6,ICAM-1 and TNF-α in kidney.Results WEJTD can alleviate the symptoms of diabetes,such as food ration,polydipsia and polyuria (P ＜ 0.05,0.01,and 0.001);Relief the pathological changes of kidney and significantly decreased glycogen deposition (P ＜ 0.001),down-regulate the increase of IL-6,ICAM-1 and TNF-α in serum and kidney (P ＜ 0.05,0.01 and 0.001),up-regulate the phosphorylation of PI3K and Akt (P ＜ 0.05,0.01,and 0.001),and inhibit the phosphorylation of NF-κB (P ＜ 0.001).Conclusion WEJTD had positive effects on kidney morphology of KK-Ay,and the underlying mechanism might be related to the regulation of PI3K-Akt and NF-κB-mediated inflammation.
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Objective To observe the changes of inflammatory factors and clinical parameters on septic patients with hemoperfusion,and to discuss the application of hemoperfusion on sepsis. Methods 43 patients with sepsis were divided into treatment group and control group randomly. In the treatment group,the patients received conventional treatment and hemoperfusion together,which performed every 24 hours,continuously for 3 times when they arrived in ICU in the first hour. The concentrations of TNF-α,IL-6,IL-10 and PAF were dynamically detected before hemoperfusion,after 24 hours,48 hours and 72 hours in treatment group. The concentrations of TNF-α,IL-6,IL-10 and PAF were compared between the two groups after 72 hours. So did the clinical parameters as WBC count,CRP,PCT and blood lactate acid. Results The concentrations of TNF-α,IL-6, IL-10 and PAF were increased significantly in the early stage of sepsis,and were decreased obviously after hemoperfusion(P < 0.01). After 72 hours treatment,the concentrations of TNF-α,IL-6 and PAF were decreased rapidly,so did the level of CRP,PCT and blood lactate acid. There were significant differences between the two groups(P < 0.05). ConclusionHemoperfusion could remove the inflammatory factor of septic patients and improve the clinical symptoms of them.
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Objective To investigate whether human bone marrow mesenchymal stem cells (hBC-MSCs) have the immune-suppression ability on the proliferation of peripheral blood mononuclear cells (PBMCs) and their pro-inflammatory cytokine production in rats,to explore what kinds of human cytokines are required for the induction of hBM-MSCs to become immune-suppressive,and to observe the effect of intravenous delivery of hBM-MSCs on tumor necrosis factor (TNF)-α transcription and expression in the core infarct areas of rats after cerebral ischemia.Methods The fetal-originated hBC-MSCs and rat PBMCs were extracted;the rat PBMCs were activated by adding 10 μg/mL concanavalin A (ConA).(1) The first experiment was divided into hBM-MSCs+PBMCs group,hBM-MSCs+PBMCs+ConA group,PBMCs group and hBM-MSCs group;CCK-8 assay was employed to detect the proliferation of these cells.(2) The second experiment was divided into hBM-MSCs+PBMCs+ConA group,PBMCs+ConA group;ELISA was used to detect the TNF-α,interferon-γ (IFN-γ) and intedeukin (IL)-10 expressions.(3) The third experiment was divided into hBM-MSCs+PBMCs (IFN-γ+IL-1α) group,hBM-MSCs+PBMCs (IFN-γ+IL-1β) group,hBM-MSCs+PBMCs (IFN-γ+TNF-α) group and hBM-MSCs+PBMCs group;CCK-8 assay was used to detect the proliferation of these cells.(4) Thirty SD rats were randomly divided sham-operated group,control group (giving normal saline after ischemia) and hBM-MSCs group (giving hBM-MSCs after ischemia,n=10);on the third d of ischemia,the TNF-α mRNA and protein expressions at the infarct areas was detected by real time PCR and Western blotting,respectively.Results (1) The optical density (OD) in the hBM-MSCs+PBMCs group was significantly increased as compared with that in the PBMCs group and hBM-MSCs group (P＜0.05);OD in the hBM-MSCs+PBMCs group was significantly increased as compared with that in the hBM-MSCs+PBMCs+ConA group (P＜0.05).(2) The TNF-α,IFN-γand IL-10 levels in the PBMCs+ConA group were (1030±196) pg/mL,(2880±250) pg/mL and (330±45) pg/mL;the TNF-α and IFN-γlevels in hBM-MSCs+PBMCs+ConA group were (160±10) pg/mL and (240±55) pg/mL,which were significantly lower than those in the PBMCs+ConA group (P＜0.05);the IL-10 level in hBM-MSCs+PBMCs+ConA group was (750±110) pg/mL,which was significantly higher than that in the PBMCs+ConA group (P＜0.05).(3) The OD in the hBM-MSCs+PBMCs(IFN-γ+IL-1α)group,hBM-MSCs+PBMCs (IFN-γ+IL-1 β) group and hBM-MSCs+PBMCs (IFN-γ+TNF-α) group was significantly decreased as compared with that in the hBM-MSCs+PBMCs group (P＜0.05).(4) The TNF-α mRNA expression in the sham-operated group,control group and hBM-MSCs group was 0.490±0.128,2.369±0.788 and 1.002±0.408;the TNF-α protein expression in the sham-operated group,control group and hBM-MSCs group was 0.144±0.028,0.314±0.029,0.240±0.029;the TNF-α protein and mRNA expressions in the hBM-MSCs group were significantly decreased as compared with those in the control group (P＜0.05).Conclusions The allogeneic transplantation of hBC-MSCs is competent in suppressing the inflammation of rats in vitro and in vivo.Furthermore,this immune-suppression ability is not innate,but cytokine stimulation dependent.The immune-suppression ability of hBM-MSCs on rat PBMCs are at least partly responsible for the therapeutic effect of hBM-MSCs transplantation into the rat models,such as ischemia stroke.
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Objecitve To study the inhibitory effect of pioglitazone on inflammation factors in patients with bladder cancer. Methods A total of 100 consecutives diagnosed as bladder cancer from Februray 2013 to Februray 2014 were individed ran-domly into experiment and control groups and each of 50 cases.All patients received the appropriate operation or chemother-apeutic regimens,and the patients in experiment group received pioglitazone (15 mg/d×12 weeks)at the same time.Then to compare expression differences of high-sensitive C reactive protein (hs-CRP),tumor necrosis factor alpha (TNF-alpha),in-terleukin (IL-6)and HOMA-IR,MCP-1,MIP-1 levels.Results The levels of hs-CRP,TNF-αand IL-6 in the two groups af-ter treatment were all lower (P 0.05).Conclusion Pioglitazone could improve clinical effect and prognosis by lowing inflam-mation factors including hs-CRP,TNF-α,IL-6,HOMA-IR,MCP-1 and MIP-1 in patients with bladder cancer.
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OBJECTIVE@#To investigate the protective effect of penehvclidine hvdrochloride on ischemia-reperfusion injury in rats.@*METHODS@#The model of ischemia-reperfusion injury was established in rats through clamping rental pedicles for 50 min followed by reperfusion. A total of 60 Wistar rats were randomly divided into 4 groups including fake surgery group, model group, low PHC dosage group and high dosage penehvclidine hvdrochloride (PHC) group. Seven days before the experiment, rats in fake surgery group and model group were given 10 mL/kg normal saline, while rats in low PHC dosage group and high dosage PHC group were given 200 and 50 mg/kg PHC, respectively. The urine volume, diet volume, Cre, PU, BUN, IL-6, IL-8, TNF-α, NO MDA concentration, SOD and GSH-Px were determined.@*RESULTS@#Compared with rats in model group, decreased urine volume, diet volume, Cre, PU, BUN, IL-6, IL-8, TNF-α, NO MDA concentration and increased SOD and GSH-Px activity could be seen in low PHC dosage group and high dosage PHC group (P<0.05).@*CONCLUSIONS@#Administration of PHC before ischemia-reperfusion injury can help protect ischemia-reperfusion injury.
Sujet(s)
Animaux , Femelle , Rats , Cytokines , Sang , Inflammation , Rein , Chimie , Stress oxydatif , Agents protecteurs , Pharmacologie , Quinuclidines , Pharmacologie , Répartition aléatoire , Rat Sprague-Dawley , Rat Wistar , Lésion d'ischémie-reperfusion , Traitement médicamenteux , MétabolismeRÉSUMÉ
Objective To observe the regulation of Toll-like receptor 4 (TLR4) signal and the release of inflammation factors after angiotensin Ⅱ (Ang Ⅱ) stimulation in rat mesangial cells under high glucose condition,revealing the innate immune-related mechanism of injury by Ang Ⅱ on mesangial cells under high glucose.Methods After synchronization,cells incubated with Ang Ⅱ (10-7 mmo/L) and/or high glucose (25 mmol/L) were used as the stimulation group,cells without stimulation were as normal control (5.6 mmol/L glucose).To determine the role of TLR4 and the adaptor myeloid differentiation factor 88 (MyD88),equal number of HBZY-1 cells were added with 10-5 mmol/L irbesartan and/or TLR4 blocker (10 mg/L) for 1 h and then incubated with Ang Ⅱ (10-7 mmo/L) and/or high glucose (25 mmol/L) for 12 h or 24 h respectively.Real-time PCR was used to analyze TLR4 mRNA and MyD88 mRNA expression after 12 h.Immunofluorescence was used to observe TLR4 protein expression after 24 h; Western blotting was used to observe TLR4,MyD88 and nuclear factor κB (NF-κB) protein; ELISA was used to detect the concentration of MCP-1,IL-6 in cell supernatant respectively.Results Compared with normal control group,TLR4 mRNA and MyD88 mRNA were highly expressed in high glucose or Ang Ⅱ-induced HBZY-1 cells (P ＜ 0.01),TLR4,MyD88 and NF-κB protein as well as MCP-1,IL-6 were also up-regulated significantly (P ＜ 0.01).Compared with high glucose or Ang Ⅱ group,MyD88 and NF-κB protein as well as MCP-1,IL-6 were further up-regulated markedly in Ang Ⅱ and high glucose costimulated group (P ＜ 0.01).In HBZY-1 cells that were preincubated with irbesartan and/or TLR4 blocker,TLR4 and MyD88 protein expression were obviously inhibited,IL-6 and MCP-1 production were also decreased remarkably compared with high glucose and/or Ang Ⅱ group (P ＜ 0.01).Conclusions High glucose and Ang Ⅱ stimulate the release of proinflammatory factors in rat glomerular mesangial cells via TLR4-MyD88 pathway.This process is inhibited by irbesartan or TLR4 blocker via modulation of the signal.Ang Ⅱ has the positive-regulation potential on the release of inflammation factors via TLR4 signal in rat mesangial cells under high glucose condition.
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Objective To observe the release of inflammation-related factors after angiotensin Ⅱ (Ang Ⅱ ) stimulation in rat tubular epithelial cells (NRK-52E), to analyze whether these effects were mediated by TLR4-MyD88 pathway, and to reveal the novel mechanism of injury by Ang Ⅱ on NRK-52E cells. Methods After synchronization, cells incubated with AngⅡ (10-7 mmol/L) were used as the stimulation group, cells without stimulation were as normal control. To determine the role of TLR4 and the adaptor MyD88, equal number of NRK-52E cells was added with 10-5 mmol/L candesartan or 20 mg/L TLR4 blocking peptide for 1 h and then incubated with Ang Ⅱ (10-7 mmol/L) respectively. RT-PCR was used to analyze TLR4 mRNA and MyD88 mRNA expression. Immunofluorescence and confocal microscopy were used to observe TLR4 protein expression. ELISA was used to detect the concentration of tumor necrosis factor-alpha (TNF-α) and heat shock protein 47(HSP47) in cell supernatant respectively. Results TLR4 and MyD88 were highly expressed in Ang Ⅱ-induced NRK-52E cells (P＜0.01), and the TNF-α and HSP47 levels were also increased markedly compared with control group (P＜0.01). In NRK-52E cells that were pre-incubated with candesartan, TLR4 and MyD88 expression were obviously inhibited,subsequently, HSP47 and TNF-α production decreased remarkably compared with Ang Ⅱ group (P＜0.01). TLR4 blocking peptide had the similar effect in a dose-dependent manner, in which its effect was dependent on inhibiting TLR4-MyD88 expression. Conclusion The mechanism of Ang Ⅱ -induced injury effect on NRK-52E cells is related to the increase of TLR4-MyD88 activity,which is followed by the enhance of TNF-α and HSP47 expression. This process is inhibited by candesartan via modulation of innate immune pathway.
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Objective To investigate the clinical significance of serum P-selection,TNF-α,hs-CRP,IL-1β, ICAM in patients with diabetic renal microangipathy, and the therapeutic mechanism of Simvastatin combined with aspirinon in treating renal microangipathy. Methods The serum levels of P-selection,TNF-α, hs-CRP, IL-1β, ICAM were determined by ELISA in all groups. Patients with diabetic renal microangipathy treated with simvastatin and as-pirinon. Results ① The serum levels of P-selection,TNF-α,hs-CRP,IL-1β,ICAM in DM groups were higher than those of normal controls(P<0.01). ②After treatment with simvastatin and aspirinon for 8 weeks in patients with di-abetic nephropathy,the serum levels of P-selection, TNF-α, hs-CRP, IL-1β, ICAM were all decreased significantly compared with those before treatment respectively (P<0.01). After treatment for 16 weeks the above indices re-mained decreased until treatment for 21 weeks (P<0.01). Conclusion ①The plasma levels of Poselection,TNF-α and hs-CRP, IL-1β, ICAM are correlated to the occurance and development of diabetic renal microangiopathy, becom-ing predicted factors in early stage of diabetic renal microangiopathy. ②The therapeutic mechanism of simvastatin and aspirinon in patients with diabetic nephropathy lies probably in the inhibition of these factors expression, thus di-rectly or indirectly affecting the prolffer-ation of mesangial cells and mesangial matrix.
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Objective: To observe the effects and immunological mechanism of continuous blood(purification)(CBP) in treatment of children with infectious shock.Methods: Twelve children with infectious shock treated with continuous veno-venus hemofiltration(CVVH) in intensive care unit(ICU) from June 2002 to October 2005 were selected as CBP treatment group,and 20 children with infectious shock without the(treatment) were selected as controls at the same time.The levels of pH,oxygenation index,HCO~-_3,base(excess(BE)),blood urea nitrogen(BUN),serum creatinine(SCr),blood pressure and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) were examined before and 24,48 hours after treatment dynamically,while the levels of tumor necrosis factor?(TNF?),interleukin1(IL1),IL6 and IL8 were detected and analyzed by SPSS 10.0 software.Results: Among the 12 patients,8 cases survived,4 cases died and the mortality rate was 33.3%.In CBP treatment group,APACHE Ⅱdecreased after treatment,and other biochemical parameters were all improved,plasma concentrations of TNF?,IL1 and IL8 decreased(P