Effect of Astragalus polysaccharide on LPS-induced cardiomyocyte apoptosis by inhibiting NF-κB and JNK signaling pathway / 中国药理学通报

Aim To study the effect of Astragalus polysaccharide (APS) on the apoptosis of cardiomyocytes induced by lipopolysaccharide (LPS) in mice and to explore its mechanism.Methods Kunming mice were treated with APS for 14 days,and intraperitoneal injection of LPS (10 mg · kg-1) was performed to establish cardiomyocyte apoptosis model in vivo,and H9c2 cells were pre-administered with APS.After 30 min,LPS (1 mg · L-1) was incubated for 24 hours to establish a model of cardiomyocyte apoptosis.Cardiac ejection fraction (EF) and left ventricular shortening score (FS) were measured using echocardiography in mice.TUNEL was carried to measure myocardial cell apoptosis.Enzyme-linked immunosorbent assay (ELISA) was employed to measure serum levels of IL-1β,TNF-α.Western blot was used to detect the expression of JNK,NF-κB signaling pathway and Bcl-2 family and caspase-3 protein in vivo and in vitro.Results LPS could significantly inhibit the left ventricular systolic function in mice and promote myocardial cell apoptosis.The levels of IL-1β,TNF-α in serum,JNK,p-JNK,Bax,caspase-3 and the concentration of NF-κB in nucleus were all increased,while the level of Bcl-2 and the concentration of NF-κB,IκB-α in cytoplasm were reduced.APS could significantly inhibit left ventricular systolic weakening in LPS-induced mice and cut down the apoptosis of cardiomyocytes.The secretion of IL-1β,TNF-α decreased to varying degrees.The protein levels of p-JNK,Bax,caspase-3 in myocardium and NF-κB in nucleus were down-regulated,but those of Bcl-2 and NF-κB,IκB-α in cytoplasm were up-regulated,and JNK had no significant change in vivo and in vitro.Conclusion APS ameliorates the LPS-induced apoptosis of myocardial cells by inhibiting NF-κB and JNK signaling pathway in mice.

Evidence-based practice of standardized gastric lavage for acute organophosphorus pesticide poisoning / 中华护理杂志

Objective To formulate standardized program of gastric lavage for acute organophosphorus pesticide poisoning(AOPP) and evaluate the effects.Methods Evidence was obtained via evidence-based approach,and recommendations were formed.The standardized program of gastric lavage for AOPP was formulated and then applied to clinical practice.The effects were evaluated by examining indicators of success rate of catheterization,the first time of gastric lavage,the time of atropinization and total usage of atropine,ChE recovery time,hospital stay,rebound rate,adverse event rate.Results After implementation,the first time of gastric lavage,the time of atropinization,total usage of atropine,ChE recovery time,and hospital stay were significantly lower than the control group (P＜0.05).Conclusion Evidence-based practice of gastric lavage for AOPP can improve therapeutic effects,reduce adverse reactions,improve quality of nursing,and promote safety of medical care.

Clinic Outcome of FLAG Regimen treating Patients with Refractory and Relapse Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of FLAG regimen for treating patients with refractory/relaspse AML and their progonistic factors.</p><p><b>METHODS</b>The 38 patients with median age 40.5 (range 13-69) were treated with FLAG regimen from July 2006 to July 2013 in hospital. According to disease status, all the patiens were divided into 4 different groups: early relapse group (3 patients), late relapse group (12 patients), first induction failure group (16 patients) and second induction failure group (7 patients); meanwhile, based on risk status, all above-mentioned patients were stratified into better (8 patients), intermediate (26 patients) and poor (4 patients) groups, respectively.</p><p><b>RESULTS</b>Twenty two cases achieved complete remission, 5 cases achieved partial remission among 38 patients. The complete remission (CR) rate was 57.9% and the overall response (OR) rate was 71.7%. The CR rate was higher in first induction failure group (12/16, 75%) than that in second induction failure group (3/7, 42.9%) and late relapse group (6/12, 50%). In better group and intermediate group, the CR rates (5/8, 62.5%; 16/26, 61.5%) were higher than that in poor group (1/4, 25%). The risk status was associated with the CR rate (P = 0.03) [OR = 25.9(95% CI 1.2-545.4)]. The intermediate risk was favorable factor to CR. Out of 22 patients with CR, 12 patients received allogenetic hematopoietic stem cell transplantation (allo-HSCT) and 10 patients received large dose of cytarabine or other regimens as consolidation treatments, 6 patients who accepted allo-HSCT are still alive. The overall survival (OS) was 25 months. The univariate analyses showed that the response to FLAG was accociated with OS [HR = 0.246, CR vs NR (95% CI 0.07-0.79) P = 0.03]. The 2-year cumulative survial rates in CR group and PR group were 62% and 48%, respectively. The 18- month cumulative survival rate was 73% in better group, 52% in intermediate group, 36% in poor group (P = 0.17); and 65% in first induction failure group and 32% in second induction failure group (P = 0.19).</p><p><b>CONCLUSION</b>The efficacy of FLAG regimen has been confirmed to be effective for patients with refractory and relapse AML. The patients who achieved remission could acquire benefit from following HSCT or other consolidation chemotherapy, and their survials could be improved.</p>

Calcineurin contributed to tumor necrosis factor alpha-induced cardiomyocyte hypertrophy in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate whether calcineurin (CaN) contribute to tumor necrosis factor alpha (TNF-alpha)-induced cardiomyocyte hypertrophy.</p><p><b>METHODS</b>The protein content was assayed with lowry's method. The cardiomyocytes volumes were measured by computer photograph analysis system. The protein synthesis was assayed with [3H]-leucine incorporation method. [Ca2+]i transient was measured by Till image system by cell-loading Fura-2/AM. The expression of CaN was determined by Western blot.</p><p><b>RESULTS</b>(1) (CsA (0.2 micromol/L), a selective CaN inhibitor, significantly suppressed the increase of protein content, [3H]-leucine incorporation and cell size induced by TNF-alpha. (2) CsA (0.2 micromol/L) significantly suppressed the elevation of the amplitude of the spontaneous Ca2+ transients induced by TNF-alpha in cultured ventricular myocytes from the neonatal rat. (3) TNF-alpha significantly increased the expression of CaN.</p><p><b>CONCLUSION</b>Ca(2+) -CaN signaling pathway are involved in cardiomyocyte hypertrophy induced by TNF-alpha in rats.</p>

Studies on apoptosis and caspase-8 and caspase-9 expressions of bone marrow cells in chronic mountain sickness / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the expressions of caspase-8 and caspase-9 mRNA, and explore the changes of apoptosis of bone marrow hematopoietic cells in patients with chronic mountain sickness (CMS).</p><p><b>METHODS</b>Of 18 CMS patients and 16 controls were enrolled in this study. The apoptotic index (AI) of bone marrow mononuclear cells (BMMNC) was measured by TUNEL technique, the levels of caspase-8 and caspase-9 mRNA in BMMNC of CMS patients and controls were determined by RT-PCR. Results (1)The AI of BMMNC in patients with CMS (8.51 ± 3.35)% was lower than that in controls (16.00 ± 4.28)% (P < 0.01); (2) The values of caspase-8 and caspase-9 mRNA were (0.28 ± 0.07) and (0.23 ± 0.08) respectively, in CMS patients, which were significantly lower than those of (0.45 ± 0.09) and (0.41 ± 0.09) respectively, in the controls (both P < 0.01); (3) Hemoglobin (Hb) value was negatively correlated with levels of caspase-8 and caspase-9 mRNA (r values were -0.52 and -0.61 respectively, both P < 0.05) in CMS patients. There was a negative correlation between AI and Hb (r value was -0.89, P < 0.01) in CMS patients. However, the significant relationship was not found between AI and level of caspase-8 or caspase-9 mRNA (P > 0.05).</p><p><b>CONCLUSIONS</b>The results showed a decrease apoptosis of BMMNCs and reduced levels of caspase-8 and caspase-9 mRNA in CMS patients, the latter might be involved in the change of BMMNCs apoptosis.</p>

Effects of kappa-opioid receptor stimulation on high glucose induced myocardial hypertrophy of neonatal rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effects of kappa-opioid receptor stimulation on high glucose induced myocardial hypertrophy of neonatal rats.</p><p><b>METHODS</b>Using cultured myocardial cells as a model, the protein content was assayed with Lowrys method. The cardiomyocytes volumes were measured by computer photograph analysis system. The level of p-ERK44/42 was determined by Western blot.</p><p><b>RESULTS</b>Compared with the control, U50488H significantly inhibited the protein content and volumes of cultured hypertrophic myocardial cells induced by high glucose. Meanwhile the role of ERK was important.</p><p><b>CONCLUSION</b>The stimulation of kappa-opioid can inhibit myocardial hypertrophy induced by high glucose, which is possibly via attenuating p-ERK.</p>

On the scientific foundation that the tissue structure of acupoints can decide and affect specificity of acupoints-organs effects / 中国针灸

Specificity of acupoints is one of the basic theories of the acupuncture and moxibustion sciences and is a very important basis to guide the clinical treatment of acupuncture and moxibustion. However, the scientific foundation of specificity of acupoints is still unclear, which has greatly restricted to the clinical effect improvement of acupuncture and moxibustion and has influenced to academic status of acupuncture and moxibustion sciences both in China and abroad. In this paper, the recent related researches are reviewed and then the key effects and mechanism that the tissue structure of acupoints can decide and affect specificity of acupoints-organs effects are analyzed and explored. It is held that acupuncture at the different tissue structure of the different depth in the different or the same acupoints will cause changes of varying qualities or degrees of visceral function because of stimulation of the different receptors in the different tissues followed by excitation of varying afferent nerve fibers.

Comparing effects of U50488H, prazosin and/or propranolol on cardiac hypertrophy induced by NE in rat / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To demonstrate the inhibitory effect of kappa-opioid receptor activation by U50488H on hypertrophy induced by NE in cultured neonatal rat cardiac myocytes and compare its effect with that of prazosin and propranolol.</p><p><b>METHODS</b>The cellular proliferation was determined with crystal violet staining. The protein content was assayed with Lowry's method. The cardiomyocytes volumes were measured by computer photograph analysis system. The protein synthesis was assayed with [3H]-lencine incorporation method.</p><p><b>RESULTS</b>(1) NE significantly induced the increase of protein content, [3H]-leucine incorporation and cell size without a concomitant increase in cell number in low serum medium. OThese responses were partially suppressed by prazosin or propranolol alone and completely abolished by both in combination. U50488H significantly inhibited the NE-induced increase of protein content, [3H]-leucine incorporation and cell size. The inhibitory effects of U50488H on NE-induced cardiac hypertrophy were greater than either prazosin or propranolol, but comparable to combination of both.</p><p><b>CONCLUSION</b>NE, acting via both alpha1- and beta-adrenergic pathway, stimulates myocyte hypertrophy. Stimulating kappa-opioid receptor significantly inhibits NE-induced cardiac hypertrophy, which may be related with alpha1- and beta1-adrenergic pathway.</p>

Ca2+ is involved in tumor necrosis factor-alpha induced cardiomyocyte hypertrophy through PI3-kinase pathway in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate whether Ca2+ contribute to cardiomyocyte hypertrophy induced by tumor necrosis factor-alpha (TNF-alpha) through PI3-kinase pathway.</p><p><b>METHODS</b>The protein content was assayed with Lowry's method. The cardiomyocytes volumes were measured by computer photograph analysis system. The protein synthesis was assayed with [3H]-leucine incorporation method. [Ca2+]i transient was measured by Till image system by cell-loading Fura-2/AM.</p><p><b>RESULTS</b>(1) TNF-alpha significantly induced the increase of protein content, [3H]-leucine incorporation and cell size. These responses were significantly suppressed by LY294002, a selective PI3-kinase inhibitor. Verapamil, L-type calcium channels antagonist, slightly attenuated TNF-alpha-induced these responses. (2) TNF-alpha increased the amplitude of the spontaneous Ca2+ transients in cultured ventricular myocytes from the neonatal rat; PI3-kinase inhibitor LY294002 could suppress the elevation induced by TNF-alpha, but calcium antagonist verapamil took the minor effects of TNF-alpha on [Ca2+]i metabolism.</p><p><b>CONCLUSION</b>Increasing the intercellular free Ca2+ level may play an essential role in TNF-alpha-induced cardiomyocyte hypertrophy through PI3-kinase pathway in rats, while L-type calcium channel takes the minor effects on it.</p>

Effects of delta-opioid receptor stimulation on survival of cultured myocardial cells upon to serum deprivation / 中国应用生理学杂志

<p><b>AIM</b>To study upon to serum deprivation if delta-opioid receptor activation has direct effect on cultured impaired cardiomyocytes survival.</p><p><b>METHODS</b>Myocardial cells of neonatal rats were cultured in vitro. The cell viability was determined with crystal violet staining uptake. The percentage of S + G2 + M in cell cycle was determined by flow cytometry. Apoptosis rates were determined by flow cytometry (FCM). The expression of Caspase-3 were investigated by Western blotting.</p><p><b>RESULTS</b>Myocardial cells of neonatal rats were cultured of serum-free in vitro, apoptotic index was significantly increased, the expression of Caspase-3 was significantly increased, free-serum induced apoptosis in cardiac myocytes after 48 h. At concentrations of 10 nmol x L(-1) - 10 micromol x L(-1), a delta opoid receptor agonist [D-Ala2, D-Leu5]-enkephalin DADLE promoted the myocardial cells survival, in a concentration-dependent manner. The optimal response was achieved at 0.1 micromol x L(-1), which increase survival index of cardiac myocyte, percentage of S + G2 + M in cell cycle, decrease apoptotic index of cardiac myocyte, and the expression activate caspase-3. Delta-opioid receptor antagonist naltrindole at 10 micromol x L(-1) inhibited the promoting effects of DADLE, which decrease survival index of cardiac myocyte, and percentage of S + G2 + M in cell cycle, increase apoptotic index of cardiac myocyte and the expression of Caspase-3.</p><p><b>CONCLUSION</b>The protective of delta-opioid receptor activation can promote survival in cultured impaired myocardial cells.</p>

Expression of GATA-1 and GATA-2 in the bone marrow of patients with Monge's disease / 中华血液学杂志

<p><b>OBJECTIVE</b>To find out how GATA-1 and GATA-2 behave in the bone marrow of patients with Monge's disease.</p><p><b>METHODS</b>The levels of mRNA in mononuclear cells (MNC) and proteins of GATA-1 and GATA-2 in the bone marrow of patients with Monge's disease and controls were determined by RT-PCR and immune cytolysis chemical method.</p><p><b>RESULTS</b>(1) All patients and controls expressed GATA-1 mRNA (Monge's disease 1.033 +/- 0.146, Control 0.458 +/- 0.076) and GATA-2 mRNA (Monge's disease 0.451 +/- 0.073, Control 0.185 +/- 0.074). All patients expressed both GATA-1 (positive cell counts 77.3 +/- 33.3, positive score 135.4 +/- 75.4) and GATA-2 ( positive cell counts 29.4 +/- 11.4, positive score 48.4 +/- 19.7). All the controls expressed GATA-1 (positive cell counts 18.1 +/- 11.3, positive score 24.2 +/- 13.4) while 12 of 20 controls expressed GATA-2 ( positive cell counts 5.4 +/- 3.0, positive score 7.3 +/- 4.2). The expression of mRNA and proteins of GATA-1 and GATA-2 in Monge's disease were higher than in controls (P < 0.01). (2) There was a positive correlation between GATA-1 and Hb (P < 0.01), as did between mRNA and proteins of GATA-1 and GATA-2. (3) Both the proteins of GATA-1 and GATA-2 located only in the cytoplasm but not the nucleus.</p><p><b>CONCLUSIONS</b>Two of inherent genes, GATA-1 and GATA-2 which were expressed at higher levels in patients with Monge's disease than in controls might play significant roles in the pathogenesis of Monge's disease.</p>

Effects and Mechanism of Adenosine A_1 Receptor Agonist on Isoproterenol Induced Hypertrophy in Cultured Neonatal Rats Myocardial Cells / 中华高血压杂志

Objective To demonstrate the inhibitory effect of adenosine A_1 receptor agonist R(-)-N6-(2-phe- nylisopropyl) adenosine (R-HA) and cross-talk between adenosine A_1 receptor and CaMKII on Isoproterenol (Iso)- induced hypertrophy in cultured myocardial cells in neonatal rats.Methods The protein synthesis was determined by incorporation of [~3H]-leucine into myocyte protein.The expression of CaMK Ⅱ ? B was determined by Western- blot.The [Ca~(2+)]i transient was measured in myocytes loaded with fura-2 by the spectrofluorometric method. Results R-PIA (1?mol/L) inhibited Iso(10 ?mol/L)-induced increase of [~3 H-]-leucine incorporation [(R-PIA: 974.8?58.6) vs (Iso:1220.8?240.5) count per min per well,P

The inhibitory effect of chronic lead exposure on CA1 LTP and ERK2 activity in rat hippocampal area / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effect of chronic lead exposure on rat hippocampal CA1 LTP and alpha-Ca2+ /calmodulin-dependent protein kinase II (alpha-CaM K II) activity in vivo.</p><p><b>METHODS</b>A stimulus bipolar electrode was placed on the Schaffer/Commissural fibers, with extra cellular microelectrode technique to record the population spike (PS) in the CA1 pyramidal, and we observed the changes of PS amplitude before and after the high frequency stimulation (HFS) of lower, mid and higher level lead exposure groups and the control group, respectively. The hippocampal CA1 alpha-CaM K II activity was determined by Western blots by using phosphorylation antibody.</p><p><b>RESULTS</b>The average changes of PS after HFS of the control group, the lower, mid and higher level lead exposure groups were 162.5%, 105.2%, 86.8%, 83.0%, respectively (P < 0.01 vs. control). Defined control a-CaM K II activity as 100, that the lower, mid and higher level lead exposure groups were 62.0 +/- 3.7, 50.8 +/- 4.0, 43.3 +/- 4.1 (P < 0.01).</p><p><b>CONCLUSION</b>Chronic lead exposure can inhibit CA1 LTP in vivo, and the decrease of alpha-CaMK II activity may play an important role in this mechanism.</p>

Effect of high glucose and high insulin on NE-induced cardiac hypertrophy of the cultured myocardial cells / 中国应用生理学杂志

<p><b>AIM</b>To study the effect of diabetes-like environment on the cardiac hypertrophy, cultured cardiomyocytes were used to study the effect of high insulin and high glucose on norepinephrine (NE)-induced cardiac hypertrophy.</p><p><b>METHODS</b>Using cultured myocardial cells as a model, the cellular hypertrophy was observed. The contracting frequency was counted by the inverted microscope, the protein content was assayed with Lowry's method, the cardiomyocytes' volumes were measured by computer photograph analysis system, the protein synthesis was assayed with [3H] leucine intake method.</p><p><b>RESULTS</b>The total cellular protein content, cellular volumes, cellular protein synthesis showed an increase in high insulin group and high glucose group compared with control group. High insulin and high glucose and NE group showed a further increase compared with high glucose and NE group.</p><p><b>CONCLUSION</b>The high insulin itself induces hypertrophy of the cultured myocardial cells slightly. Meanwhile, imitating diabetes-like environment with high insulin and high glucose and NE can further accelerate hypertrophy of the cultured myocardial cells.</p>

Inhibitory effects of kappa-opioid receptor stimulation on cultured myocardial cells / 中国应用生理学杂志

<p><b>AIM</b>In order to study the effects of kappa-opioid receptor activation, we used cultured cardiomyocytes to study the inhibitory effects of U50,488H on cellular proliferation, protein content in the presence or absence of nor-binaltorphimine (nor-BNI).</p><p><b>METHODS</b>The cellular proliferation was determined with crystal violet staining and the protein content was assayed with Lowry's method.</p><p><b>RESULTS</b>A kappa-opioid receptor agonist U50,488H at 0.1 micromol/L-10 micromol/L inhibited the cellular proliferation and protein content of cultured myocardial cells in a dose-dependent manner. The inhibitory effects of U50,488H were completely blocked by pretreatment with nor-BNI, a specific kappa-opioid receptor antagonist at 1 micromol/L.</p><p><b>CONCLUSION</b>U50,488H inhibited the cultured myocardial cells' growth. The inhibitory effects of U50,488H are involved in mediating the action of kappa-opioid receptor stimulation.</p>