Distribution of memory B cell subsets in peripheral blood of children with frequently relapsing nephrotic syndrome / 中国当代儿科杂志

OBJECTIVES@#To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease.@*METHODS@#A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS (n=20) and non-FRNS (NFRNS; n=15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed.@*RESULTS@#Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD+ memory B cells, and IgE+ memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group (P<0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups (P<0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM+IgD+ memory B cells, IgM+ memory B cells, IgE+ memory B cells, IgD+ memory B cells, and IgG+ memory B cells (P<0.05) and a significant increase in the percentage of class-switched memory B cells (P<0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups (P<0.05) and a significantly lower level of albumin than the control group (P<0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE+ memory B cells (P<0.05).@*CONCLUSIONS@#Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE+ memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.

Effect of hydrogen sulfide on antiatherosclerosis in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effect of hydrogen sulfide (H2S) on artherosclerosis (AS) and its mechanism in rats.</p><p><b>METHODS</b>125 healthy male SD rats of the weight (210 +/- 10) g were randomly divided into 5 groups: control group, AS model group, AS + low-dose NaHS (2.8 micromol/(kg x d)) group, AS+ middle-dose (14 micromol/(kg x d)) NaHS group, AS+ high-dose NaHS (28 micromol/(kg x d)) group. The atherosclerotic model was established by feeding high grease food and injecting large doses of VitD3. The rats were using NaHS by peritoneal injection for 12 weeks. 5 rats were executed in each group before the experiment and in the weeks of 3, 6, 9, 12 after the experiment, respeotively. The blood fat was analyzed by automatic biochemistry analysator. H2S content in serum was detected by the method of deproteinization. The pathological damage of vessels was observed and scored by HE stain. The expression of VEGF in the vessel tissue was detected by immunohistochemistry staining.</p><p><b>RESULTS</b>Compared with the control group at contemporaneity, both serumal triglyceride (TG) and cholesterol (TC) increased significantly in the AS model group after rat feeded 3, 6, 9, 12 weeks, and scores of the artery pathological damage also increased obviously from the 6th week to the 12th week (P < 0.01), as well as artherosclerosis plaque appeared, displaying as lipid plaque in the positive part. The serumal H2S concentration decreased obviously, from (44.98 +/- 2.06) micromol/L of before feeding to (38.56 +/- 2.26), (32.96 +/- 2.38), (28.63 +/- 0.92), (23.55 +/- 0.92) nnol/L of after feeding 3, 6, 9, and 12 weeks, respectively, and lower than that of control at contemporaneity (44.72 +/- 0.85), (43.71 +/- 0.59), (41.96 +/- 0.97), (39.87 +/- 1.25) micromol/L, respectively ( P < 0.01), and VEGF expression of the vascular tissue also increased (P < 0.01). Compared with the AS model group, all of above indexes in rat of the low-dose of NaHS group did not appear any obvious change. The serumal H2S concentration in rat of the middle-dose NaHS began increase at the 6 week after rat feeded (36.13 +/- 0.3 vs. 32.96 +/- 2.38 micronol/L, P < 0.05), and continuously increased at the 9th and the 12th week (33.07 +/- 1.14 vs. 28.63 +/- 0.92 micromol/L, 30.16 +/- 0.2 vs. 23.55 +/- 0.92 micromol/L; P < 0.01, respectively). The serumal H2S concentration in high-dose NaHS groups, increased from the 3th to the 12th week (41.25 +/- 0.80, 38.71 +/- 0.46, 35.31 +/- 0.62, 33.38 +/- 0.78 micromol/L, respectively, P < 0.01). The rat serumal TC in both middle and high-dose NaHS groups, decreased from the 3th to the 12th week (P < 0.01), and TG began decrease from the 3th and the 6th week to the 12th week after rat feeded, respectively (P < 0.05, P < 0.01). Both of the pathological damage scores and the expression of VEGF decrease from the 6th week to the 12th week (P < 0.05). The correlation analysis showed that H2S in serum had a negative correlation with both pathological damage scores (r = -0.917, P < 0.01) and the expression of VEGF (r = -0. 885, P < 0.01). But it had no obvious correlation with serumal TG and TC.</p><p><b>CONCLUSION</b>The formation and development of artherosclerosis has a close correlation with the depressing of endogenous H2S. Administration of exogenous H2S could raise the H2S concentration of serum in artherosclerosis, which might improve the damage of vessels and inhibit the expression of VEGF.</p>

Involvement of endothelin-1 in hypoxia-induced cardiomyocyte apoptosis / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effect of endogenous endothelin-1 (ET-1) on cardiomyocyte apoptosis induced by hypoxia and its possible mechanism.</p><p><b>METHODS</b>Cultured neonatal rat cardiomyocytes were divided into control group and ET receptor antagonist group. Control group was given DMEM only and ET receptor antagonist group was treated with ET receptor subtype A (ET(A)) receptor antagonist BQ610 and BQ123 or ET(B) receptor antagonist BQ788 and subjected to hypoxia for 24 h. The presence of apoptosis in cardiomyocytes was evaluated by TUNEL analysis and flow cytometry (FCM).</p><p><b>RESULTS</b>TUNEL analysis showed that the percentage of positive apoptotic cells in BQ610 5 micromol/L group was 13.2% +/- 3.7%, significantly lower than that in hypoxia group (24.2% +/- 2.2%, P < 0.01). FCM showed that BQ123 (0.04, 0.2 and 1.0 micromol/L) inhibited hypoxia-induced cardiomyocyte apoptosis and increased cardiomyocyte survival rate in a dose-dependent manner, while BQ788 did not show such effects.</p><p><b>CONCLUSION</b>These findings suggest that endogenous ET-1 aggravates hypoxia-induced cardiomyocyte apoptosis and this effect is mediated through ET(A) receptor-dependent pathways.</p>

Endothelin signaling in cardiac myocyte / 中国医学科学院学报

Endothelin can affect the contractile properties of cardiacmyocyte, stimulate myocyte growth and myofibrillogenesis, and increase resistance to apoptosis by intracellular signaling pathways. This article briefly reviews the regulative effects of these signaling pathways including protein kinase C, mitogen activated protein kinase, and phosphoinositide 3'-OH kinase/protein kinase B.

Inflammation is involved in the organ damage induced by sinoaortic denervation in rats / 第二军医大学学报

Objective:The present study was designed to test the hypothesis that inflammation is involved in the end-organ damage(EOD) induced by sinoaortic denervation(SAD) in rats.Method:SAD was performed in male Sprague-Dawley rats at the age of 10 weeks.Under anaesthesia,aortic nerves were cut and the sinus region of the carotid artery was stripped and painted with 10% phenol.Pathological evaluation of EOD and the determination of plasma or tissue levels of the factors related to inflammation,including thromboxane B2(TXB2) interleukin-1(IL-1),tumour necrosis factor α(TNF-α) and reactive oxygen species(ROS) were performed at 16 weeks after SAD.Pathological evaluation of EOD included heart weigh ratio,myocardial and blood vessel hydroxyproline and collagen volume fraction,glomerular injury score and number of infiltrating inflammatory cells.Indomethacin(20 mg/kg per day,orally) or vitamin E(100 mg/kg per day,orally) was administered for 12 weeks,beginning from4 weeks after SAD,to observe their effects on SAD-induced EOD.Results:There were significant fibrosis and inflammatory infiltration in the myocardium and blood vessels,represented by higher hydroxyproline and collagen volume fraction,and a large amount of inflammatory cells in the tissues of SAD rats.Heart weight and kidney glomerular injury score were significantly higher in ed significantly after SAD.Indomethacin and vitamin E significantly decreased the contents of some factors related to inflammation in SAD rats.Both drugs also alleviated myocardial and vessel fibrosis,inflammatory infiltration and kidney damage.Conclusion:Inflammation is involved in the organ damage induced by SAD in rats.

Inflammation is involved in the organ damage induced by sinoaortic denervation in rats / 第二军医大学学报

Objective:The present study was designed to test the hypothesis that inflammation is involved in the end-organ damage(EOD) induced by sinoaortic denervation(SAD) in rats.Method:SAD was performed in male Sprague-Dawley rats at the age of 10 weeks.Under anaesthesia,aortic nerves were cut and the sinus region of the carotid artery was stripped and painted with 10% phenol.Pathological evaluation of EOD and the determination of plasma or tissue levels of the factors related to inflammation,including thromboxane B2(TXB2) interleukin-1(IL-1),tumour necrosis factor α(TNF-α) and reactive oxygen species(ROS) were performed at 16 weeks after SAD.Pathological evaluation of EOD included heart weigh ratio,myocardial and blood vessel hydroxyproline and collagen volume fraction,glomerular injury score and number of infiltrating inflammatory cells.Indomethacin(20 mg/kg per day,orally) or vitamin E(100 mg/kg per day,orally) was administered for 12 weeks,beginning from4 weeks after SAD,to observe their effects on SAD-induced EOD.Results:There were significant fibrosis and inflammatory infiltration in the myocardium and blood vessels,represented by higher hydroxyproline and collagen volume fraction,and a large amount of inflammatory cells in the tissues of SAD rats.Heart weight and kidney glomerular injury score were significantly higher in ed significantly after SAD.Indomethacin and vitamin E significantly decreased the contents of some factors related to inflammation in SAD rats.Both drugs also alleviated myocardial and vessel fibrosis,inflammatory infiltration and kidney damage.Conclusion:Inflammation is involved in the organ damage induced by SAD in rats.

Effects of urotensin II on isolated rat hearts under normal perfusion and ischemia reperfusion / 生理学报

To shed light on cardiac effects of the potent vasoconstrictive peptide urotensin II (U II), Langendorff-perfused isolated rat hearts were consecutively perfused with 0.1, 1 and 10 nmol/L U II, for 5 min at each dose, followed by 5-min washout. Moreover, isolated hearts subjected to 20-min global no-flow ischemia were reperfused with U II (1 or 10 nmol/L) for 20 min. Heart function parameters including heart rate, left ventricular pressure and dP/dt were monitored; content of protein and myoglobin, and activity of lactate dehydrogenase (LDH) in coronary effluent were determined; malondialdehyde (MDA) in myocardium and [(125)I]-U II binding sites in plasma membrane were measured after the completion of perfusion. The results showed that: (1) In normal rat hearts, the coronary flow was decreased and the heart function was suppressed by U II dose-dependently, and these changes were not abolished by washout. The leakage of cardiac protein, myoglobin and LDH increased with the increment of U II, but it diminished rapidly after washout. In contrast, MDA content in U II -treated myocardium was not statistically different from that in normal myocardium. (2) Ischemia-reperfusion caused significant decreases in coronary flow, suppression of heart function, and leakage of protein and LDH. In U II -reperfused hearts, all these disorders were significantly aggravated and myocardial MDA content significantly increased (P<0.01), to a greater extent in the presence of higher dose of U II. (3) The maximal binding capacity (B(max)) of U II receptors in plasma membrane from ischemia-reperfusion myocardium increased significantly as compared with that of normal myocardium (20.53+/-1.98 vs 14.65+/-1.78 fmol/mg pr, P<0.01), while Kd remained unchanged. These results indicate that U II caused injury to the isolated rat hearts under normal perfusion, and worsened the injury of the hearts under ischemia-reperfusion, in which U II receptors were up-regulated.

Preventive effect of endothelin-1 pretreatment on hypoxia-induced injury in cultured neonatal rat cardiomyocytes / 生理学报

This study was designed to observe the effects of endothelin-1 (ET-1) pretreatment on hypoxia-induced injury and changes in [Ca(2+)](i) in cultured neonatal rat cardiomyocytes. The activity of lactate dehydrogenase (LDH) and superoxide dismutase (SOD), and the content of malondialdehyde (MDA) in the supernatant were determined in the cultured cardiomyocytes subjected to a 12-h hypoxia induced by a 3% O(2)-5% CO(2) atmosphere at 37 with or without ET-1 pretreatment. [Ca(2+)](i) was measured with Ca(2+)-sensitive fluorescent probe fluo-3/AM under a laser scanning confocal microscope. Fluorescence intensity emitted from fluo-3/AM-loaded cells reflected the concentration of [Ca(2+)](i). The hypoxia model used in [Ca(2+)](i) measurement was established by continously perfusing cardiomyocytes for 30 min with 95% N(2)-5% CO(2) saturated DMEM solution containing 1 mmol/L Na(2)S(2)O(4). Pretreatment with ET-1 consisted of three cycles of ET-1 perfusion (5 min for each) followed by ET-1-free DMEM solution (10 min for each) prior to hypoxia. The results showed that (1) after incubation in a 3% O(2)-5% CO(2) hypoxic atmosphere for 12 h, the activity of LDH and the content of MDA in the supernatant significantly increased from 19.33+/-1.03 U/L to 43.33+/-1.21 U/L and from 0.91+/-0.03 nmol/L to 1.71+/-0.02 nmol/L, respectively, whereas the activity of SOD decreased from 33.48+/-1.15 U/ml to 16.93+/-1.11 U/ml (P<0.01). In hypoxic cardiomyocytes pretreated with 0.01-1 nmol/L ET-1, LDH release and supernatant MDA content were decreased, while SOD activity was enhanced dose-dependently (P<0.01). (2) The spontaneous calcium transient in cultured cardiomyocytes terminated at 29+/-1.5 s and [Ca(2+)](i) increased by 107+/-13.2% during perfusion of hypoxic solution (P<0.001) at the end of 30 min. ET-1 (0.01-1 nmol/L) increased the frequency of [Ca(2+)](i) transient in cultured cardiomyocytes in a dose-dependent manner (P<0.01). The termination of [Ca(2+)](i) transient and the elevation of [Ca(2+)](i) caused by hypoxia were postponed by pretreatment with 0.01-1 nmol/L ET-1 (P<0.01). These results show that pretreatment with 0.01-1 nmol/L ET-1 attenuates hypoxia-induced injury and [Ca(2+)](i) changes in cultured neonatal cardiomyocytes, indicating a cyto-protective role of ET-1 pretreatment.

Roles of ACh receptors in the effects of corticosterone on presympathetic neurons in the ventrolateral medulla of rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the roles of acetylcholine (ACh) receptors in the rapid effects of corticosterone (CORT) on the presympathetic neurons in the rostral ventrolateral medulla (RVLM) of rats, and study the non-genomic mechanism of glucocorticoid (GC) in the integration of sympathetic cardiovascular activity.</p><p><b>METHODS</b>The effects of microelectrophoresis of CORT on the discharge of the presympathetic neurons in the RVLM were observed by extracellular recording in urethane-anaesthetized rats. The responses of atropine (a blocker for M type of ACh receptor, ATR), d-tubocurarine (a blocker for N1 type of ACh receptor, d-TC) and hexamethonium (a blocker for N2 type of ACh receptor, C6) to the effects of CORT on the presympathetic neurons were investigated respectively.</p><p><b>RESULTS</b>Totally 33 presympathetic neurons in the RVLM were recorded. Among them the firing rate of 25 (76%) presympathetic neurons was increased by microelectrophoresis of CORT. The effects of CORT were also positively correlated with the currents. In the other 8 presympathetic neurons, had was shown no effect after microelectrophoresis of CORT. In 10 presympathetic neurons, which discharge was increased by CORT, microelectrophoresis of ATR decreased the firing rate of these presympathetic neurons (P < 0.05), and did not fully block the excitatory effect induced by CORT. In both 7 and 6 presympathetic neurons, application of d-TC and C6 had no effect on these neurons respectively, and did not fully block the excitatory effect induced by CORT.</p><p><b>CONCLUSION</b>CORT had rapid excitatory effects on the presympathetic neurons in the RVLM, which effect might be independent on ACh receptors.</p>

Effect of urotensin II on the nitric oxide production in neonatal rat cardiomyocytes / 生理学报

The aim of this study was to investigate the effect of urotensin II (U II) on the nitric oxide (NO) production in cultured neonatal rat cardiomyocytes. The endothelial nitric oxide synthase (eNOS) mRNA expression was assessed by semi-quantitative reverse transcription-polymerase chain reaction. The activity of nitric oxide synthase (NOS) and NO content in cardiomyocytes were measured. The current results showed that U inhibited eNOS mRNA expression, the NOS activity and the NO production of cardiomyocytes. U II (0.1 micromol/L) inhibited the NOS activity and the NO production in cardiomyocytes in a time-dependent manner. These results suggest that the cardiovascular effect of U II might be partially associated with NO production in cultured neonatal rat cardiomyocytes.

Effect of intravenous injection of corticosterone on the presympathetic neurons in rostral ventrolateral medulla of rats / 第二军医大学学报

Objective: To study the role of glucocorticoid i n the integration of sympathetic nervous system and cardiovascular activity. Methods: Neurons in the rostral ventrolateral medulla (RVLM) were extracelluarly recorded and identified as the presympathetic neurons of adult rats. The spontaneous discharge of the presympathetic neurons in the RVLM were observed by bolus intravenous injection of corticosterone (50, 100, 150 μg/kg） . Results: The firing rate of 12 presympathetic neurons was incr eased by intravenous application of corticosterone (P<0.05), and this effect showed a dose-dependent manner. The latency of excitatory effect was (104±2 5) s. Conclusion: Corticosterone can rapidly excite the presym pathetic neurons in the RVLM, this action might be involved in the integration o f sympathetic nervous system through the “rapid membrane effects”.

Effect of intravenous injection of corticosterone on the presympathetic neurons in rostral ventrolateral medulla of rats / 第二军医大学学报

Objective: To study the role of glucocorticoid i n the integration of sympathetic nervous system and cardiovascular activity. Methods: Neurons in the rostral ventrolateral medulla (RVLM) were extracelluarly recorded and identified as the presympathetic neurons of adult rats. The spontaneous discharge of the presympathetic neurons in the RVLM were observed by bolus intravenous injection of corticosterone (50, 100, 150 μg/kg） . Results: The firing rate of 12 presympathetic neurons was incr eased by intravenous application of corticosterone (P<0.05), and this effect showed a dose-dependent manner. The latency of excitatory effect was (104±2 5) s. Conclusion: Corticosterone can rapidly excite the presym pathetic neurons in the RVLM, this action might be involved in the integration o f sympathetic nervous system through the “rapid membrane effects”.