Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 36
Filter
1.
Journal of Sun Yat-sen University(Medical Sciences) ; (6): 607-616, 2023.
Article in Chinese | WPRIM | ID: wpr-979214

ABSTRACT

ObjectiveTo investigate the analgesic action and mechanism of intrathecal 2R, 6R-hydroxynorketamine (2R, 6R-HNK) on spared nerve injury (SNI)-induced chronic neuropathic pain (CNP) in female mice. MethodsSNI was used to establish acute and chronic CNP models in female mice. The mice were randomly divided into different groups with administration of vehicle, 2R, 6R-HNK or S-ketamine (10 mg/kg intraperitoneal injection/i.p. or 7, 21 μmol/L intrathecal injection/i.t.) at 3 weeks after or 30 min/1 d before operation (n = 3 - 7 mice/group). The curative or preventive effect of 2R, 6R-HNK was evaluated by mechanical paw withdrawal threshold (PWT) and the analgesic efficiency. Finally, immunofluorescence and RT-PCR of dorsal root ganglion (DRG) and spinal dorsal horn (SDH) were used to explore the possible mechanisms. ResultsCompared with vehicle, intrathecal injection of 2R, 6R-HNK largely reversed SNI-induced bilateral mechanical allodynia in a delayed-and-dose-dependent way. Among them, 21 μmol/L 2R, 6R-HNK reached its maximum analgesic efficiency (75.32±7.69) % at 2 d. Pre-intrathecal delivery of 2R, 6R-HNK also delayed the development of bilateral mechanical hypersensitivity 2 - 3 d induced by SNI. Mechanically, 2R, 6R-HNK reversed not only the abnormal excitability of neurons in bilateral DRG and superficial SDH, but also the upregulation of calcitonin gene-related peptide (CGRP) and brain-derived nerve growth factor (BDNF) in DRG. ConclusionIntrathecal administration of 2R, 6R-HNK exerts an analgesic effect against CNP, probably via suppressing abnormal neuronal excitability in ascending pain pathway as well as down-regulating CGRP and BDNF expression in DRG neurons.

2.
Journal of Sun Yat-sen University(Medical Sciences) ; (6): 395-402, 2023.
Article in Chinese | WPRIM | ID: wpr-973235

ABSTRACT

ObjectiveTo investigate whether there exists gender differences in mechanical pain hypersensitivity induced by the subcutaneous injection of macrophage colony-stimulating factor (M-CSF) in normal mice and to explore the preliminary mechanism. MethodsThirty 10-week-old C57BL/6J mice were randomly divided into three groups, (n = 10 mice/group, half male and half female). The albumin control group (BSA, 0.3 μg), low dose M-CSF group (L M-CSF, 0.075 μg) and high dose M-CSF group (H M-CSF, 0.3 μg) received 50 μL BSA or M-CSF injected subcutaneously into the left medial thigh once daily for 3 consecutive days. Before and after drug administration, von-Frey mechanical sensitivity test was used to detect the mechanical paw withdrawal threshold (PWT) in each group. Immunofluorescence was performed to examine the expression changes of Ionized calcium-binding adaptor molecule 1 (Iba1) in skin, calcitonin gene-related peptide (CGRP) and phosphorylated ERK1/2 (p-ERK) in L5-L6 DRG and lumbar spinal dorsal horn. ResultsIn female mice, only high dose of M-CSF caused mechanical allodynia, whereas in male mice both doses produced marked allodynia. Mechanically, high-dose M-CSF induced massive aggregation of subcutaneous macrophages (marked by Iba1) in male and female mice, but more dramatic dependence in female mice. Similar gender differences were also found in the increase of p-ERK and CGRP expression in dorsal root ganglion (DRGs). Notably, CGRP expression was especially elevated in the fibers of DRG in male mice. Correspondingly, the expressions of p-ERK and CGRP+ terminals in the superficial spinal dorsal horn of male mice were significantly higher than those of female mice after M-CSF treatment. ConclusionSubcutaneous injection of M-CSF triggers sexual dimorphism in mechanical pain hypersensitivity, which is related with differential changes in peripheral macrophage expansion and sensitization of the nociceptive pathway.

3.
Biomedical and Environmental Sciences ; (12): 135-145, 2023.
Article in English | WPRIM | ID: wpr-970301

ABSTRACT

OBJECTIVE@#This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol (RSV) regulate necroptosis during Vibrio vulnificus (V. vulnificus)-induced sepsis and the potential mechanism.@*METHODS@#The effect of RSV on V. vulnificus cytolysin (VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays. Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V. vulnificus-induced sepsis mouse model.@*RESULTS@#RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells. RSV also inhibited the inflammatory response, had a protective effect on histopathological changes, and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages, lung, spleen, and liver tissues of V. vulnificus-induced septic mice in vivo. Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V. vulnificus-induced septic mice. RSV also improved the survival of V. vulnificus-induced septic mice.@*CONCLUSION@#Our findings collectively demonstrate that RSV prevented V. vulnificus-induced sepsis by attenuating necroptosis, highlighting its potency in the clinical management of V. vulnificus-induced sepsis.


Subject(s)
Animals , Mice , Necroptosis , Resveratrol/therapeutic use , Vibrio vulnificus , Sepsis/drug therapy , Blotting, Western
4.
Journal of Sun Yat-sen University(Medical Sciences) ; (6): 224-232, 2020.
Article in Chinese | WPRIM | ID: wpr-817693

ABSTRACT

@#【Objective】Due to the tough nature of skin tissue and a high presence of RNases,the isolation of skin RNA by the classical Trizol method presents a challenge. Therefore,we adapted and tested different sample treatment protocols to improve the Trizol method for high- quality extraction of skin RNA.【Methods】In this study,normal skin of mice processed by different treatments(Tri:submersion Trizol;Pro:RNA sample protector;Cry:cryopreservation in liquid nitrogen frozen and then - 80 ℃ refrigerator;LNG:liquid nitrogen grinding;Cut:scissor cutting)were used as the experimental groups. Spinal cord tissue(Sp)was used as the reference group,and skin tissue of mouse psoriasis model induced by imiquimod(IMQ)was used as the validation group. We compared skin RNA concentration,purity and integrity, as well as IL- 1β mRNA expression extracted by conventional Trizol methods(1-Tri,Nor)and modified Trizol methods(2-Tri,LNG-Tri,Tri-Cut,Pro),which were determined by UV spectrophotometry,agar gel electrophoresis and quantitative reverse transcription PCR(qRT- PCR).【Results】① Compared with spinal cord(Sp),the total RNA of normal skin tissue extracted with the same classical Trizol method(1-Tri)was with lower yields,more obvious DNA contamination and 5S RNA bands,and higher IL-1β mRNA relative expression,suggesting that skin tissue was relatively special and the classical Trizol methods of skin RNA extraction should be improved. ② Among the different treatment methods of skin tissue,2-Tri and LNG-Tri methods resulted in higher RNA concentrations,lower RNA degradation and lower DNA contamination,and the expression of IL-1β mRNA was closer to normal levels. More importantly,the skin RNA samples extracted by the 2-Tri method can reflect more realistically the variation of IL-1β mRNA expression between normal and psoriasiform groups.【Conclusion】Improved 2-Tri or LNG-Tri method has the advantage of high quality of total RNA,and 2-Tri can more reliably reflect the mRNA expression pattern under physiological and pathological conditions.

5.
Journal of Sun Yat-sen University(Medical Sciences) ; (6): 518-524, 2019.
Article in Chinese | WPRIM | ID: wpr-817671

ABSTRACT

@#【Objective】To investigate the analgesic and degenerated regularity of paravertebral ozone injection in the discogenic pain model of SD rats ,and to reveal the mechanism of analgesic effect of ozone preliminarily.【Methods】 Male SD rats(n = 65)were randomly divided into control group(n = 15),model group(n = 25)and ozone group(n = 25). The L5- 6 intervertebral discs of SD rats in model group and ozone group were punctured to establish discogenic pain models. Ozone was injected paravertebrally in ozone group rats on the 22nd day after modeling. The rats in control group were normal. A quantitative allodynia assessment technique and MRI were used to detect the 50% mechanical withdrawal threshold(50%MWT)and Pfirrmann grade of L5-6 intervertebral discs at different time intervals. The expression of tumor necrosis factor-α(TNF- α)and calcitonin gene-related peptide(CGRP)in left dorsal root ganglion and sciatic nerve were detected by western blot.【Results】The 50% MWT of both hind paws were different from each other in three groups at each time after the 22nd day after modeling(P < 0.05). In the ozone group,the 50% MWT rose on the 22nd day after modeling(left 7.6±6.8,right 3.6±1.0,P < 0.05 vs pre-ozone injection),and reached the peak on the 24th day after modeling(left 10.6±8.2,right 7.9±6.7,P < 0.05 vs pre-ozone injection),and maintained this level until the 56th day after molding. In the ozone group,the L5-6 intervertebral disc degeneration was apparently visible compared with model group(P < 0.05). The expression of TNF- α and CGRP in dorsal root ganglion and sciatic nerve were different from each other in three groups(model>ozone>control,P < 0.05).【conclusions】Paravertebral ozone injection can alleviate the pain of discogenic pain model rats,but aggravates the degeneration of the lumbar disc. Paravertebral ozone injection can reduce the expression of TNF-α and CGRP in the sciatic nerve and dorsal root ganglia of discogenic pain model rats.

6.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 967-972, 2019.
Article in Chinese | WPRIM | ID: wpr-843954

ABSTRACT

Objective: To investigate the protective effect of exenatide on patients with diabetic kidney disease in early stage and its mechanism. Methods: From January 2015 to August 2018, a total of 80 patients with diabetic kidney disease in early stage in The First Affiliated Hospital of Soochow University were randomly divided into observation group and control group with 40 in each. Patients in control group were treated with olmesartan and metformin orally. Those in observation group were treated with exenatide subcutaneously on the basis of the same treatment in control group. Blood glucose, blood lipid, renal function, serum advanced glycosylation end products (AGEs), cyclic adenosine phosphate (cAMP), serum oxidative stress and peripheral blood mononuclear cells (PBMC) were compared before and after treatment. Results: After 24 weeks of treatment, the levels of FBG, HbAlc, MBG, SDBG, BGFR and MAG were significantly lower in observation group than in control group (P0.05). However, the systolic and diastolic blood pressure in control group was significantly decreased after treatment (P0.05). Conclusion: Exenatide has a certain protective effect on diabetic kidney disease in early stage. It may be related to decreasing AGEs production, improving oxidative stress and regulating cAMP/PKA signaling pathway.

7.
Acta Physiologica Sinica ; (6): 883-893, 2019.
Article in Chinese | WPRIM | ID: wpr-781386

ABSTRACT

In this study, we improved the culture method of mouse hippocampal primary microglia to obtain hippocampal ramified microglia with high activity and purity, which were resemble to the resting status of normal microglia in healthy brain in vivo. Hippocampal tissue was excised from 2-4-week-old SPF C57BL/6J mice and cut into pieces after PBS perfusion, and then manually dissociated into the single-cell suspension by using Miltenyi Biotec's Adult Brain Dissociation Kit. The tissue fragments such as myelin in the supernatant were removed by debris removal solution in the kit. The cell suspension was incubated with CD11b immunomagnetic beads for 15 min at 4 °C. To obtain high-purity microglia, we used two consecutive cell-sorting steps by magnetic activated cell sorting (MACS). After centrifugation, the cells were resuspended and seeded in a 24-well culture plate. The primary microglia were cultured with complete medium (CM) or TIC medium (a serum-free medium with TGF-β, IL-34 and cholesterol as the main nutritional components) for 4 days, and then were used for further experiments. The results showed that: (1) The cell viability was (56.03 ± 2.10)% by manual dissociation of hippocampus; (2) Compared with immunopanning, two-step MACS sorting allowed for efficient enrichment of microglia with higher purity of (86.20 ± 0.68)%; (3) After being incubated in TIC medium for 4 d, microglia exhibited branching, quiescent morphology; (4) The results from qRT-PCR assay showed that the levels of TNF-α, IL-1β and CCL2 mRNA in TIC cultured-microglia were similar to freshly isolated microglia, while those were much higher in CM cultured-microglia after incubation for 4 d and 7 d (P < 0.05). Taken together, compared to the conventional approaches, this modified protocol of mouse hippocampal primary microglia culture by using MACS and TIC medium enables the increased yield and purity of microglia in the quiescent state, which is similar to normal ramified microglia in healthy brain in vivo.


Subject(s)
Animals , Mice , Cell Culture Techniques , Methods , Cell Separation , Methods , Cells, Cultured , Hippocampus , Magnetics , Mice, Inbred C57BL , Microglia , Cell Biology
8.
Chinese Journal of Pathophysiology ; (12): 1109-1114, 2018.
Article in Chinese | WPRIM | ID: wpr-701247

ABSTRACT

AIM:To analyze the imageological changes of acute and chronic central serous chorioretinopathy (CSC) by 2 types of optical coherence tomography (OCT). METHODS:A retrospective analysis was performed, inclu-ding data of 60 eyes from 56 patients with CSC diagnosed by conventional eye examination, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA), which were divided into acute group (28 eyes of 28 patients) and chronic group (32 eyes of 28 patients) according to imageological examinations and duration (6 months). Optical coher-ence tomography angiography (OCTA) and spectral domain optical coherence tomography ( SD-OCT) were performed to study the vessel density of the chorioretinal leyers and the integrity of the outer retinal structure. RESULTS:In the pa-tients with chronic CSC, OCTA in 4 eyes ( 12.50% ) revealed the presence of a distinct choroidal neovascularization (CNV), while no evidence of CNV in ICGA was observed. However, no sign of CNV in acute CSC group both on OCTA and ICGA was found. The occurrence of 'dark areas' in chronic CSC was much higher than that in acute CSC ( P <0.01). In addition, the integrity of the outer retinal structure (defined as tissue between external limiting membrane and retinal pigment epithelium) in acute group was significantly better than that in chronic group ( P <0.01). CONCLU-SION:Our study demonstrates the existing secondary CNV that is not demonstrated by ICGA in the chronic CSC patients, and the different characteristics of retinochoroid structures between acute and chronic CSC in OCTA and SD-OCT are ob- served. Chronic CSC has more severe structural changes.

9.
Military Medical Sciences ; (12): 13-16, 2018.
Article in Chinese | WPRIM | ID: wpr-694306

ABSTRACT

Objective To develop chitosan composite keratinocyte growth factor-2 mutant(KGF-2M)temperature-sen-sitive dressing and evaluate its physicochemical properties and dynamic release rule were used.Methods Chitosan, chi-tosan quaternary ammonium salt,β-glycerophosphate and other adjuvant materials to configure different formulations which were compounded with KGF-2M in order to develop temperature-sensitive dressing.Gelling time, temperature,the release rate of KGF-2M and other indicators were measured to analyze the physical and chemical properties of the temperature -sen-sitive dressing.Results Chitosan-KGF-2M composite dressing with temperature-sensitive properties was obtained by opti-mizing the formulation components of chitosan and related adjuvant materials.When the liquid dressing was above 35℃,it could be converted from liquid to solid gelatin within 10 minutes.The compound KGF-2M released from the gel was more than 98%at 4 h,and its bioactivity remained stable.Conclusion The thermo-sensitive gel has the characteristics of good conformability,moisturizing(moisture),isolation,wound healing,and a controlled release effect,which has great potential in wartime for wound repair.

10.
China Journal of Chinese Materia Medica ; (24): 2105-2108, 2013.
Article in Chinese | WPRIM | ID: wpr-346433

ABSTRACT

To study the optimum preparation process and stability of beta-cyclodextrin inclusion compound in volatile oil of Cinnamomum longepaniculatum leaves. The saturated aqueous solution method was adopted to prepare inclusion compounds for an orthogonal test. The inclusion compound productivity and the inclusion rate were taken as indexes for screening the inclusion processes. The inclusion effect was evaluated with the infrared spectrophotometry and TLC, and the stability under conditions of high temperature, high humidity and strong light was detected. Under optimum preparation conditions for inclusion, the ratio between volatile oil and beta-cyclodextrin was 1: 8 (mL: g), that between beta-cyclodextrin and water was 1: 15, the inclusion temperature was 40 degrees C, and the inclusion time was 3 h. The results of spectrophotometry and TLC showed that the optimum conditions can generate beta-cyclodextrin inclusion compound in volatile oil of C. longepaniculatum leaves with certain light resistance, thermo-stability and hygro-stability. Therefore the optimum inclusion process features simple operation and stable inclusion compounds.


Subject(s)
Chromatography, Thin Layer , Cinnamomum , Chemistry , Drug Stability , Oils, Volatile , Chemistry , Plant Leaves , Chemistry , Spectrophotometry, Infrared , Technology, Pharmaceutical , beta-Cyclodextrins , Chemistry
11.
Chinese Journal of Applied Clinical Pediatrics ; (24): 1187-1190, 2013.
Article in Chinese | WPRIM | ID: wpr-733121

ABSTRACT

Objective To summarize the thoracolumbar injuries and treatment in children and adolescents.Methods Since 2000,clinical data,surgical methods,efficacy and mechanism of 177 children and adolescents with thoracolumbar spine injury treated in Honghui Hospital of Xi'an Jiaotong University School of Medicine were analyzed and compared.Treatment was in accordance with easy typing method of Honghui Hospital of Xi'an Jiaotong University School of Medicine.The principles and systematic methods of analysis of such damage was emphasized.Clinical,physiological and psychological effects were observed.Results According to easy typing method of Honghui Hospital of Xi'an Jiaotong University School of Medicine.Ⅰ a-c 77 cases,Ⅱ a 40 cases.Twenty-seven cases of Frankel A were unchanged.There were 28 cases that had been restored to Frankel C in 30 cases of Frankel B.There were 2 cases that had been restored to Frankel D in 30 cases of Frankel B.There were 2 cases that had been restored to Frankel D in 27 cases of Frankel C.There were 25 cases that had been restored to Frankel E in 27 cases of Frankel C.There were 30 cases that had been restored to Frankel E in 30 cases of Frankel D.In 177 patients,imaging,VAS,ODI,SF-36,DPQ,MMSE,Barthel and psychology had achieved significant differences before and after treatment for follow-up of 7-12 months(all P < 0.05).Conclusions Simple type is easy to grasp.It applies to children and adolescents treatment of thoracic and lumbar spine injury to good effect.It is a reasonable treatment strategy.

12.
Chinese Journal of Pediatrics ; (12): 587-592, 2012.
Article in Chinese | WPRIM | ID: wpr-348579

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the relationship between the prognosis and clinical factors of primary vesicoureteral reflux (VUR) patients under the condition of non-surgical treatment.</p><p><b>METHOD</b>The medical records of the patients who were diagnosed as VUR by micturating cystourethrography (MCU) from January 2000 to December 2009 in Children's Hospital of Fudan University underwent non-surgical treatment, and followed up for more than one year then had repeated MCU, were retrospectively reviewed.</p><p><b>RESULT</b>A total of 73 children (30 boys, 43 girls) were included in this study. The percentage of mild reflux (grade I-II) was 19.2% (14/73), that of moderate reflux (grade III) was 53.4% (39/73), and that of severe reflux (grade IV-V) was 27.4% (20/73). Among 73 patients, 27 (37.0%) patients were found to have renal damage. The average interval of repeated MCU was (1.29 ± 0.40) years (1 - 2 years). After follow-up, it was found that the reflux grade was relieved in 41 (56.2%) patients, of whom 27 (37.0%) patients achieved complete resolution, 32 (43.8%) patients did not have remission in reflux grade, of whom 13 (17.8%) patients had worsened reflux grade. Logistic regression analysis showed that VUR patients with renal damage at initial diagnosis was an important clinical factor to affect reflux remission (P = 0.000), complete resolving (P = 0.008) and result in worsening (P = 0.002).</p><p><b>CONCLUSION</b>A certain proportion of primary VUR patients could get reflux grade self-resolution, it was also quite common in severe VUR patients. VUR patients with renal damage at initial diagnosis was an important clinical factor affecting the reflux grade prognosis. Mild and moderate VUR patients with renal damage were at risk of worsening. VUR patients with high reflux grade had normal renal status could still get remission or even disappearance of VUR. But severe VUR patients with renal damage were still recommended to receive surgical therapy.</p>


Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , Anti-Bacterial Agents , Therapeutic Uses , Cicatrix , Kidney Diseases , Epidemiology , Pathology , Prognosis , Retrospective Studies , Risk Factors , Severity of Illness Index , Survival Rate , Urinary Tract Infections , Epidemiology , Urography , Vesico-Ureteral Reflux , Drug Therapy , Pathology
13.
Chinese Journal of Pediatrics ; (12): 819-824, 2011.
Article in Chinese | WPRIM | ID: wpr-356367

ABSTRACT

<p><b>OBJECTIVE</b>To deeply understand prognosis of pediatric cases with lupus nephritis (LN) treated in our hospital and analyze the prognostic factors.</p><p><b>METHOD</b>One hundred and one patients were enrolled, who were diagnosed as lupus nephritis in our hospital during the period from Jan. 1996 to Dec. 2007. Clinical data were retrospectively analyzed; the observation was ended on 31(st) Dec. 2009. Patients were divided into renal biopsy group and non renal biopsy group; group A (type I + II LN), group B (type III + IV LN) and group C (type V LN); CTX group (cyclophosphamide) and MMF group (mycophenolate mofetil); remission group (complete remission and partial remission) and ineffective group (treatment failure and death). Medication non-compliance means (1) the interval of CTX pulse was more than 45 days or treatment course less than 6 times; (2) patients discontinued MMF or other immunosuppressant on themselves more than a week ago. SPSS 11.0 software Life-Tables method was used to analyze cumulative survival rates.</p><p><b>RESULT</b>(1) Three and five years' patient survival rates were 93.59% and 87.80% respectively. Three and five years' kidney survival rates were 100% and 91.12% respectively. (2) Univariate analysis showed that induction remission were related to five factors, including whether received renal biopsy (χ(2) = 9.023, P = 0.003), different pathological types (χ(2) = 9.437, P = 0.009), different induction drug (χ(2) = 4.610, P = 0.032), treatment compliance (χ(2) = 18.716, P = 0.000) and proteinuria amount (χ(2) = 8.013, P = 0.046), and maintenance remission were related to the former four factors (χ(2) = 10.209, P = 0.001;χ(2) = 7.757, P = 0.021;χ(2) = 4.206, P = 0.04;χ(2) = 24.571, P = 0.000). (3) Multivariate analysis showed that maintenance remission was mainly related to medication-compliance (χ(2) = 9.818, P = 0.002). Poor medication compliance mainly occurred in non renal biopsy group (χ(2) = 9.569, P = 0.002). (4) In renal biopsy group, 15 cases showed a small amount proteinuria, 4 of them were proved as severe pathological type LN (2 cases type III, 1 case type IV and 1 case type V). (5) In group B, no medication non-compliance occurred, and the efficacy of MMF and CTX had no significant difference (P = 0.405).</p><p><b>CONCLUSION</b>The main affecting factor of remission rate was medication compliance. In type III and IV lupus nephritis, the efficacy of MMF and CTX were no significant difference. The poor outcome of non-renal biopsy group may be due to unclear pathological classification and poor medication compliance. We strongly recommend that SLE patients with mild abnormal results of urinalysis should receive renal biopsy.</p>


Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Biopsy , China , Follow-Up Studies , Kidney , Pathology , Lupus Nephritis , Diagnosis , Therapeutics , Medication Adherence , Prognosis , Remission Induction , Survival Analysis
14.
Chinese Journal of Cardiology ; (12): 440-445, 2011.
Article in Chinese | WPRIM | ID: wpr-272226

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the effects of valsartan and carnitine on cardiomyocyte Calpain-1 and Bcl-xl expressions of dogs with chronic alcohol intake-induced cardiomyopathy.</p><p><b>METHODS</b>Dogs were randomly assigned into 4 groups (n = 7 each): (1) alcohol fed (free access to 5%, 1(st) week; 10% 2(nd) week; 500 ml 25% bolus plus free access to 5% from 3 to 24 weeks, A); (2) alcohol + valsartan (5 mg×kg(-1)×d(-1), B); (3) alcohol + carnitine (300 mg×kg(-1)×d(-1), C); (4) Control (D). After six months, all animals were assessed for left ventricular (LV) function by echocardiography. The Bad and Bcl-xl protein expressions were evaluated by immunohistochemistry. The expression of Calpain-1 protein was determined with Western blot. Myocardial morphology was quantified on HE stained slices and under electron microscopy. The terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) was performed for apoptosis analysis.</p><p><b>RESULTS</b>Compared with group D, LVEDD and LVESD were significantly increased while EF and FS significantly decreased in group A. In alcohol fed group, expressions of Bad and Calpain-1 protein were significantly increased while Bcl-xl protein expression was downregulated, all changes could be significantly attenuated by intervention with valsartan and carnitine (all P < 0.05).</p><p><b>CONCLUSION</b>These data suggest that alcohol could promote cardiac myocyte apoptosis, reduce cardiac function and aggravate myocardial remodeling which valsartan and carnitine could reduce alcoholic cardiomyopathy by downregulating Calpain-1 and Bad protein expression and upregulating expression of Bcl-xl protein.</p>


Subject(s)
Animals , Dogs , Apoptosis , Calpain , Metabolism , Cardiomyopathy, Alcoholic , Metabolism , Pathology , Carnitine , Pharmacology , Disease Models, Animal , Myocytes, Cardiac , Metabolism , Tetrazoles , Pharmacology , Valine , Pharmacology , Valsartan , bcl-Associated Death Protein , Metabolism , bcl-X Protein , Metabolism
15.
Chinese Medical Journal ; (24): 390-395, 2011.
Article in English | WPRIM | ID: wpr-321496

ABSTRACT

<p><b>BACKGROUND</b>Tenascin-x, an extracellular matrix glycoprotein exclusively expressed in fibroblasts, can mediate fibrosis in the presence of collagen. Therefore, we have investigated its potential role in facilitating myocardial fibrosis and cardiac remodeling via the transforming growth factor-β1 and peroxisome proliferator-activated receptor γ (TGFβ(1)-PPARγ) pathway in alcoholic cardiomyopathy (ACM).</p><p><b>METHODS</b>Experimental animals were divided into control (group A) and tenascin-x knock-out groups (group B) receiving alcohol. Six months post treatment, cardiac ejections fraction (EF), fractional shortening (FS), left ventricle end-diastole internal diameter (LVEDd) and collagen column fraction (CVF) were observed. Tenascin-x, smad-3, TGFβ(1), smad-7 and PPARγ protein expression levels were detected by Western blotting.</p><p><b>RESULTS</b>Six months post treatment, EF and FS values were higher in group B than in group A (P < 0.05 and P < 0.01, respectively), while LVEDd and CVF were lower in group B (P < 0.05 and P < 0.01, respectively). Tenascin-x, smad-3 and TGFβ(1) protein expression levels were higher in group A, while smad-7 and PPARγ levels were lower than in group B (P < 0.01), as measured by immunohistochemistry and Western blotting. Tenascin-x protein expression was negatively correlated with EF, FS, smad-7 and PPARγ, and positively correlated with LVEDd, CVF, smad-3, and TGFβ(1) (P < 0.001).</p><p><b>CONCLUSION</b>Tenascin-x is an initiator of myocardial fibrosis and ACM development via upregulation of TGFβ(1) and downregulation of PPARγ.</p>


Subject(s)
Animals , Mice , Rats , Blotting, Western , Cardiomyopathy, Alcoholic , Metabolism , Immunohistochemistry , Microscopy, Electron , Myocardium , Metabolism , PPAR gamma , Metabolism , Smad3 Protein , Metabolism , Smad7 Protein , Metabolism , Tenascin , Metabolism , Transforming Growth Factor beta1 , Metabolism
16.
Chinese Journal of Cardiology ; (12): 875-879, 2010.
Article in Chinese | WPRIM | ID: wpr-244124

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the outcome of ST-elevation acute myocardial infarction (STEMI) patients complicated pre-hospital cardiac arrest underwent percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>From September 2004 to November 2008, 1446 consecutive patients with acute STEMI underwent PCI in our department. 49 out of 1446 patients complicated by pre-hospital cardiac arrest. Clinical outcome including total mortality, adverse cardiac events, stroke and bleeding events during the hospitalization period and within 1 year after discharge was compared between patients with or without pre-hospital cardiac arrest.</p><p><b>RESULTS</b>PCI success rate was similar (85.7% vs. 88.8%, P = 0.497) while the incidence of in-hospital cardiogenic shock 22.4% vs. 3.0%, P < 0.001 and cardiac arrest (44.9% vs. 5.9%, P < 0.001) and in-hospital mortality (36.7% vs. 2.0%, P < 0.001) were significantly higher in patients with pre-hospital cardiac arrest than patients without pre-hospital cardiac arrest. Time from symptom onset to emergency treatment, asystole as initial rhythm, Glasgow coma scale (GCS ≤ 7) and cardiogenic shock on admission were independent risk factors of in-hospital death in patients with pre-hospital cardiac arrest. During follow up, incidences of overall mortality, re-infarction, revascularization and stroke were similar between the two groups.</p><p><b>CONCLUSIONS</b>STEMI patients with pre-hospital cardiac arrest undergoing emergency PCI are facing higher risk of cardiogenic shock and cardiac arrest and higher in-hospital mortality compared to those without pre-hospital cardiac arrest. However, the post-hospital discharge outcome was similar between the two groups.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Angioplasty, Balloon, Coronary , Emergency Treatment , Heart Arrest , Therapeutics , Hospital Mortality , Myocardial Infarction , Mortality , Therapeutics , Treatment Outcome
17.
Chinese Medical Journal ; (24): 2718-2723, 2009.
Article in English | WPRIM | ID: wpr-307831

ABSTRACT

<p><b>BACKGROUND</b>No-reflow phenomenon during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) is a predictive factor of continuous myocardial ischemia, ventricular remodeling and cardiac dysfunction, which is closely associated with a worse prognosis. This study aimed to evaluate intracoronary nitroprusside in the prevention of the no-reflow phenomenon in AMI.</p><p><b>METHODS</b>Ninety-two consecutive patients with AMI, who underwent primary PCI within 12 hours of onset, were randomly assigned to 2 groups: intracoronary administration of nitroprusside (group A, n = 46), intracoronary administration of nitroglycerin (group B, n = 46). The angiographic results were observed. The real-time myocardial contrast echocardiography (RT-MCE), including contrast score index (CSI), wall motion score index (WMSI), transmural contrast defect length (CDL) and serious WM abnormal length (WML) were recorded at 24 hours and 1 week post-PCI. High sensitivity C-reactive protein (Hs-CRP) was examined by immune rate nephelometry. N-terminal prohormone brain natriuretic peptide (NT-proBNP) was tested with enzyme-linked immunosorbent assay. Patients were followed up for six months. Major adverse cardiac events (MACE) were recorded.</p><p><b>RESULTS</b>The incidence of final TIMI-3 flow in group A was much higher than that in Group B (P < 0.05), final corrected TIMI frame count (cTFC) in group A decreased significantly than that in group B (P < 0.01). The CSI, CDL/LV length, WMSI and WL/LV length in group A were significantly lower than that in group B (P < 0.01). Levels of Hs-CRP and NT-proBNP at 1 week post-PCI decreased significantly in group A than that in group B (P < 0.01). Patients were followed up for 6 months and the incidence of MACE in group A was significantly lower than that in group B (P < 0.05).</p><p><b>CONCLUSION</b>Intracoronary nitroprusside can improve myocardial microcirculation, leading to the decrease of the incidence of no-reflow phenomenon and better prognosis.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Acute Disease , Angioplasty, Balloon, Coronary , C-Reactive Protein , Coronary Angiography , Coronary Circulation , Follow-Up Studies , Myocardial Infarction , Blood , Therapeutics , Natriuretic Peptide, Brain , Blood , Nitroprusside , Peptide Fragments , Blood
18.
Chinese Journal of Cardiology ; (12): 324-329, 2009.
Article in Chinese | WPRIM | ID: wpr-236481

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of carnitine on cardiac function, collagen contents, peroxisome proliferator-activated receptor alpha (PPARalpha) and retinoid X receptor alpha (RXRct) expressions in a rat alcoholic cardiomyopathy modeL.</p><p><b>METHODS</b>Adult male Wistar rats were randomly divided into alcohol group (A) , alcohol/carnitine group (B) and control group. Six months later, protein expressions of collagen I, collagen III, matrix metalloproteinase-9 (MMP-9) and Smad-3 were determined by immunohistochemical staining. Protein expressions of PPARalpha and RXRalpha were detected by Western blot.</p><p><b>RESULTS</b>Expressions of collagen I, collagen III, MMP-9 and Smad-3 were significantly increased in groups A and B compared to group C (P < 0.01 or P < 0.05). Expressions of PPARalpha and RXRalpha (0.156 and 0.192, respectively, in group A; 0.248 and 0.385, respectively, in group B) were decreased compared to group C (P < 0.01 or P < 0.05). These changes were significantly attenuated by carnitine (all P < 0.05, group B vs. group A). Moreover, PPARalpha and RXRalpha positively correlated with EF and FS, and negatively correlated LVEDd, collagen I , collagen III, MMP-9 and Smad-3 (all P < 0.01).</p><p><b>CONCLUSION</b>PPARalpha and RXRalpha downregulation is significantly correlated with cardiac dysfunction in this alcoholic cardiomyopathy model, carnitine ameliorated the cardiac fibrosis and remodeling possibly through upregulating the metabolic pathways of PPARalpha and RXRalpha.</p>


Subject(s)
Animals , Male , Rats , Cardiomyopathy, Alcoholic , Metabolism , Pathology , Carnitine , Therapeutic Uses , Myocardium , Metabolism , Pathology , PPAR alpha , Metabolism , Rats, Wistar , Retinoid X Receptor alpha , Metabolism
19.
Chinese Journal of Cardiology ; (12): 630-635, 2008.
Article in Chinese | WPRIM | ID: wpr-355924

ABSTRACT

<p><b>OBJECTIVE</b>To explore the time course of renin-angiotensin system (RAS), peroxisome proliferator-activated receptor (PPAR) alpha and PPARgamma change in an animal model of alcoholic cardiomyopathy (ACM).</p><p><b>METHODS</b>Adult rats were divided into three groups: ACM group (A, 10% alcohol as drinking water plus 5 ml 60% alcohol.kg(-1).d(-1) per gavage in the 1st week; 10% alcohol as drinking water plus 10 ml 60% alcohol/kg bid per gavage in the 2nd week, 20% alcohol as drinking water plus 15 ml 60% alcohol/kg bid per gavage during week 3 to week 16), ACM/ARB group(B, A + Irbesartan 5 mg.kg(-1).d(-1) per gavage) and control group (C). mRNA expressions and activities of renin, angiotensin, ACE and AT1 were detected with RT-PCR and radioimmunoassay methods. Protein expressions of PPARalpha and PPARgamma were determined with Western blot. Echocardiogram, optic (HE) and electron microscope examinations were also performed. Parameters were obtained at 2 or 6 months (n = 7 - 10 each).</p><p><b>RESULTS</b>Compared with group C, LV/BW ratio was significantly increased and LVEF significantly decreased, activities and expressions of Ang I, Ang II and renin were gradually increased, protein expressions of PPARalpha were gradually decreased at 2 and 6 months in group A (all P < 0.05). These changes could be partly attenuated by Irbesartan.</p><p><b>CONCLUSION</b>Activated RAS and decreased protein expressions of PPARalpha and PPARgamma contributed to the development of ACM.</p>


Subject(s)
Animals , Male , Rats , Cardiomyopathy, Alcoholic , Metabolism , Disease Models, Animal , PPAR alpha , Metabolism , PPAR gamma , Metabolism , Rats, Wistar , Renin-Angiotensin System
20.
Chinese Journal of Endemiology ; (6): 636-640, 2008.
Article in Chinese | WPRIM | ID: wpr-643297

ABSTRACT

Objective To observe the variation of enzymatic activity and areas and bulk of focus of heart injuries by using controllable catheter to ablate epicardial tmsue of rabbits and focus underneath atrioventrieular ring narcosis with 20% urethane(4 ml/kg)and divided into three groups.Each group included 7 rabbits.Anterior wallepieardium of left ventricle was ablated thirty seconds in each group(10,20 and 30 W)with self-made ablationspheroid microwave antenna,refilling with high pressure normal saline at same time.Then all of the rabbits were sacrificed respectively and their ventricular myocardium were taken out to undergo immunohistochemistry in order to display suceinate dehydrogenase(SDH).Also amplitude Wag measured in order to calculate areas of heart injuries.(8F)wag delivered to the pre-selected sites around atrioventricular ring of thirty-two healthy dogs,which had beenin intravenous narcosis with pentobarbital sodium(30 mg/kg).The dogs were divided into four groups(40,50,60 and 80 w) and two time points(60 and 120 s),by the combined method of X-ray and endocardial electrocardiograph,the microwave antenna could be confirmed to be located at the accurate position between anterior and posterior wall close to septum of left/right ventricle.After ventricular myocardium had been taken out,amplitude were measuredin order to calculate bulk of heart injuries by 1/6×3.14 x long×wide×deep.In addition.the histological changesand transmural injury were examined by optic microscope.Results In each group,the centre of injuries wagenzyme deficiency locus.The diameter and areag of heart injuries enlarged significantly(3.99.±0.41),(5.20±0.25),(6.31±0.37)mm and(12.53±2.56),(21.19±3.14),(30.96±3.76)mm2 with the increased microwave power level(10、20、30 W).Group comparison had statisficM significance(F=76.8,58.5;P<0.01 or <0.05).A total of 116points were ablated.The myocardial lesion showed ellipse in shape,and continuous symmetrical coagulationnecrosis under microscopic examination.There was a clear demarcated line around tlle myocardial tissue and fewparietal thmmbus.There were 16 transmura]injuries and five-with lung damage.The bulk of lesion aroundatrioventrieular ring hag been significantly enlarged(46.7±2.5),(51.1±2.7),(133.2±3.4),(141.8±3.9),(248.5±6.2),(260.3±6.5),(313.7±9.5),(327.4±10.5)with the increased microwave power level(40,50,60and 80 W)and/or distance of microwave ablation(60 and 120 s).Groups comparison had statistical significance(F=31.16,27.85;all P<0.01).In each time point,the lesion bulks had conspicuous distinction of statistics.In the same microwave power,the time wag longer,the bulk was larger(P<0.01).Conclusions The more the microwave power level and time,the severe the heart injuries is.It is possible to use the microwave energy to ablate the deep focus under endocardium around atrioventricular ring.

SELECTION OF CITATIONS
SEARCH DETAIL