Mechanosensitive ion channel Piezo1 induces senescence of atrial fibroblasts by activating β-catenin / 中国药理学通报

Aim To observe whether the mechanosensitive ion channel Piezo1 was involved in the senescence of atrial fibroblasts by activating β-catenin based on our previous study which found marked increase of Piezo1 mRNA in senescent atrial fibroblasts. Methods Primary mouse atrial fibroblasts (MAFs) were isolated from male C57BL/6 mice (3-4 weeks) by enzyme digestion, and tert-butyl hydroperoxide (TBHP) was used to induce the senescence of cells. The ratio of senescent cells was detected by senescence-associated β-galactosidase (SA-β-Gal) staining. The protein levels of Piezo1, β-catenin/p-β-catenin, senescence-associated proteins p53 and p21 in the cells treated with TBHP (100 μmol · L

Effects of Shensongyangxin capsule on ventricular electrical properties, structural remodeling and cardiac function in diabetic rats / 中国病理生理杂志

[ABSTRACT]AIM:TodeterminetheeffectsofShensongyangxincapsule(SSYX)ontheventricularelectrical properties, structural remodeling and cardiac function in the rats with diabetes mellitus (DM).METHODS:Male SD rats (n=45) were randomly divided into control group (n=15), DM group (n=15) and SSYX group (n=15).The rats in DM group and SSYX group were injected with streptozotocin (60 mg/kg, ip), while the rats in control group were given normal saline (1 mL/kg, ip).The blood samples were collected 72 h after treatment for determining the blood glucose lev-els in DM group and SSYX group .The model rats in SSYX group were administered with SSYX (1 g· kg-1 · d-1 , ig) for 6 weeks, while the other rats received normal saline (2 mL· kg-1· d-1, ig).The echocardiography was used to assess the cardiac function , and the lead II electrocardiogram was also recorded in all the animals .The radioimmunoassay and Masson trichrome staining were used to measure the plasma levels of endothelin -1 (ET-1) and the collagen deposition in the ventricles, respectively.A whole Langendorff-perfused heart model was used to conduct the electrophysiologic study .The monophasic action potential ( MAP) and the ventricular effective refractory period ( VERP) were recorded in the left anteri-or free wall ( LAF) , and the burst pacing was used to induce ventricular arrhythmia ( VA) .RESULTS: Compared with control group, the VERP, action potential duration (APD), QT interval, incidence of VA, degree of myocardial fibrosis and plasma level of ET-1 were increased , while the cardiac function was declined in DM group .Compared with DM group , the VERP, APD, QT interval, incidence of VA, degree of myocardial fibrosis and plasma level of ET-1 were all de-creased, while the cardiac function was improved in SSYX group .CONCLUSION: SSYX attenuates the electrical and structural remodeling and improves the cardiac function in DM rats .

Expression of micro RNA-29a and 133a in myocardium of atrium of per-sistent atrial fibrillation model dog / 中国病理生理杂志

AIM:To investigate the effects of microRNA-29a and 133a expression in the atrium on atrial fibril-lation (AF) and fibrosis.METHODS:Chronic rapid atrial pacing was used to establish the persistent AF dog model , and the sham group was also set up .The cardiac ultrasound measurement was used for determining the cardiac structure size . The Masson 3 color staining were used to evaluate the stage of fibrosis .The expression of microRNA-29a and 133a in the left atrium ( LA) was detected by real-time transcriptase polymerase chain reaction .RESULTS: Compared with before modeling , no statistical difference of atrial dilatation and decreased ejection fraction in the model dogs with persistent AF was observed (P>0.05).Compared with sham group, the degree of fibrosis and collagen volume fraction (CVF) in per-sistent AF model group were increased obviously (P<0.05).The expression of microRNA-29a and 133a were decreased obviously (P<0.01, P<0.05).CONCLUSION:Structural remodeling of the atrium and atrial fibrosis are the essential for development and maintenance of atrial fibrillation .Down-regulation of microRNA-29a and 133a expression may be very important molecular mechanism for atrial structural remodeling in the persistent AF model dogs .

Comparison between the effect of mycophenolate mofetil and sildenafil on the vascular structure and cell factors in rats with pulmonary arterial hypertension / 中华风湿病学杂志

Objective To investigate the effect of mycophenolate mofetil (MMF) and sildenafil on the systolic pulmonary arterial pressure (SPAP),right ventricular hypertrophy index (RVHI),pulmonary arterial and heart structural of pulmonary arterial hypertension (PAH) rat models.Methods The rat models of monocrotaline (MCT)-PAH were developed.Sprague-Dawley male rats were randomly assigned into the control group,the MCT group,the MMF (40 mg·kg-1·d-1) group,the sildenafil (20 mg·kg-1·d-1) group,and the MMF (40 mg·kg-1·d-1) + sildenafil (20 mg·kg-1·d-1) group.The SPAP and RVHI were measured,and the pulmonary arterial and heart structural changes were observed for all rats.Statistical analysis were performed by one-way ANOVA and rank-sum test.Results ① SPAP of the MMF group,the sildenafil group and the MMF + sildenafil group were (31±8),(37±8),(29±6) mmHg,while that of the MCT group was (53±7) mmHg,the difference was statistically significant (P＜0.01).The RVHIs in the MMF group,the sildenafil group and the MMF+sildenafil group were reduced [(0.365±0.038),(0.407±0.047),(0.325 ±0.459) respectively] when compared with the MCT group (0.543±0.080),the difference was statistically significant (P＜0.01).The SPAP between the MMF+sildenafil group and the sildenafil group was statistically significantly different (P＜0.05),and the RVHI difference between the MMF+ sildenafil group and the sildenafil group was statistically significant (P＜0.05).② The wall thic-kness/tubes diameter of the MMF group (0.355±0.074) and the MMF+sildenafil group (0.289±0.017) were reduced when compared with that of the MCT group [(0.466±0.006)],the difference was statistically significant (P＜0.05).The wall thickness/tubes diameter of the MMF group (0.355±0.074) were reduced compared with the sildenafil group (0.455±0.006),and the difference was statistically significant (P＜O.05).In addition,the wall thickness/tubes diameter of the MMF+ sildenafil group (0.289±0.017) was reduced when compared with that of the sildenafil group (0.455±0.006),and the difference was statistically significant (P＜ 0.05).Conclusion Both sildenafil and MMF can reduce the SPAP and RVHI of PAH rat models induced by MCT.MMF and sildenafil can reduce wall thickness as well.

Effects of hydrogen sulphide on the proliferation and apoptosis of human fetal lung fibroblasts during hypoxia / 中国药理学通报

Aim To investigate the effects of endogenous and exogenous hydrogen sulfide(H_2S)on the proliferation and apoptosis of human fetal lung fibroblasts.Methods Human fetal lung fibroblasts were cultured under 2% O2～93% N_2～5% CO_2 for 24 h to produce hypoxia.Cells were divided into 6 groups:(1)Hypoxia group(N_2);(2)N_2+600 μmol·L~(-1) NaHS group;(3)N_2+1 200 μmol·L~(-1) NaHS group;(4)N_2+6 400 μmol·L~(-1) NaHS group;(5)N_2+400 μmol·L~(-1) cysteine(Cys)group;(6)N_2+200 μmol·L~(-1) S-adenosyl-L-methionine(SAM)group.After they were cultured for 24 h, MTT assay was used to evaluate the cell proliferation, and flow cytometry was used to detect cell apoptosis.Results Compared with N_2 group, 600 and 1 200 μmol·L ~(-1) NaHS(H_2S donor)significantly reduced proliferation induced by hypoxia of human fetal lung fibroblasts(P <0.01)without effects on apoptotic rates of cells(P >0.05)and 6 400 μmol·L~(-1) NaHS increased apoptosis of human fetal lung fibroblasts during hypoxia significantly(P <0.05), although no effects were found on proliferation of cells(P >0.05).In addition, Cys, substrate of cystathionine β-synthetase(H2S synthase, CBS) or SAM(activator of CBS)did not affect proliferation of human fetal lung fibroblasts induced by hypoxia(P >0.05), whereas apoptotic rates were increased significantly compared with that of N_2 group(P <0.05).Conclusions Endogenous and exogenous hydrogen sulfide can inhibit proliferation induced by hypoxia and promote apoptosis of human fetal lung fibroblasts, suggesting endogenous hydrogen sulfide may play a protective role through lung fibroblasts by inhibiting the pulmonary vascular structural remodeling caused by hypoxia.

An experimental study on the effects of cilazapril and valsartan on atrial structural remodeling in atrial fibrillation dogs / 中国实用内科杂志

Objective To investigate the effects of Cilazapril and Valsartan on atrial structural and functional remodeling and its mechanism in atrial fibrillation(AF)dogs induced by chronic rapid atrial pacing.Methods Twenty-seven AF dog models were built by the First Affiliated Hospital of Harbin Medical University from Mar.2006 to Oct.2006.The experimental dogs were randomly divided into sham-operated group(n=6),control group(n=7),Cilazapril group(n=7)and Valsartan group(n=7).The dogs in control group,Cilazapril group and Valsartan group were paced at 400 bpm for 6 weeks.The dogs in Cilazapril and Valsartan group received Cilazapril(1 mg?kg-1?d-1)and Valsartan(30 mg?kg-1?d-1)1 week before rapid atrial pacing until pacing stop respectively.Transthoracic and transoesophageal echocardiographic examinations were performed to detect changes in structure and function of left atrium and left atrial appendage,before and after 6-week rapid atrial pacing.Atrial collagen volume fraction(CVF)was analyzed by Masson staining.The expression of ERK1 and ERK2 in the atrial tissue were tested by immunohistochemistry.TUNEL technique was used to detect the atrial cell apoptosis.Results (1)Compared with the control group,the LA and LAA volumes were significantly smaller,LAEF,LAAEF,V-LAA+ and V-LAA-were dramaticaly higher in the Cilazapril group and the Valsartan group after 6-week rapid atrial pacing.(2)Compared with the control group,the incidence of apoptosis,CVF and the expression of atrial ERK1 and ERK2 decreased dramatically in the Cilazapril group and the Valsartan group.Conclusion Cilazapril and Valsartan could prevent atrial fibrosis and cell apoptosis in the atrial fibrillation dogs induced by chronic rapid atrial pacing.

EXPERIMENTAL STUDY OF PATHOLOGICAL CHANGES IN PULMONARY VESSELS AND THEIR MECHANISMS UNDERLYING HYPOXIC PULMONARY HYPERTENSION IN RATS / 解放军医学杂志

A model of hypoxic pulmonary hypertension (HPH) was reproduced in rats by exposing them to chronic hypoxia environment corresponding to 5km level. At 10d,20d, 30d after hypoxia in hypoxia groups and control group, the pulmonary vascular structural changes were observed with optical microscope, histochemistry and electronic microscope. The changes in hypoxia groups were as follows: ①the wall of small pulmonary arteries of every calibre showed marked thickening compared with that in control group, and the main changes involved smooth muscle cells(SMC)proliferation and collagen deposition in the vessels wall; ② SMC proliferation, muscularization of non myocytic arteries and partial myocytic arteries were observed in intra acinar pulmonary arteries, so the counts of muscular arteries significantly increased compared with control group( P

Valsartan reduces the recurrence of atrial fibrillation and delays atrial structural remodeling in patients with paroxysmal atrial fibrillation / 解放军医学杂志

Objective To evaluate the curative effect of valsartan associated with low-dose amiodarone on the recurrence of atrial fibrillation (AF), the left atrial diameter (LAD), P wave dispersion (Pd) and the maximum P wave duration (Pmax) in patients with paroxysmal AF. Methods 76 patients with paroxysmal atrial fibrillation (PAF) were randomized to valsartan (test group) and placebo (placebo group), both associated with low-dose amiodarone, and were followed up for 18 months. The patients were asked to report any episode of symptomatic atrial fibrillation and to perform an ECG as early as possible. AF load, Pmax, Pd and LAD were measured before and at the 6th, 12th, and 18th months after the treatment. Results At least one ECG-documented episode of AF was reported in 16% of the patients in test group and in 41% in placebo group, the difference was significant(P

Impact of endogenous hydrogen sulfide on pulmonary vascular structural remodeling and vasoactive peptides in rats with high pulmonary blood flow / 中国药理学通报

Aim To explore the impact of endogenous hydrogen sulfide on pulmonary vascular structural remodeling and vasoactive peptides in rats with high pulmonary blood flow. Methods Thirty-two male SD rats, weighing 120~140 g, were randomly divided into shunt group (n=8), shunt+PPG (propargylglycine)group (n=8), control group (n=8) and control+PPG (n=8). Rats in shunt group and shunt+PPG group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. Rats in shunt+PPG group and control+PPG group were intraperitoneally injected with an inhibitor of endogenous H2S generation enzyme-PPG at a dose of 37.5 mg?kg-1 each day. After 4 weeks of experiment, the morphologic changes including micro-and ultra-structural changes of pulmonary arteries of rats were observed under optical microscope and electro-microscope, respectively. H2S concentration in lung tissue was evaluated by sensitive modified sulfide electrode method. Endothelin-1 (ET-1), atrial natriuretic peptide (ANP), calcitonin gene related peptide (CGRP) and adrenomedullin (ADM) were calculated by radioimmunoussay kit. Results After 4 weeks of shunt, lung tissue H2S level increased significantly (P

Changes of Type Ⅰ Collagen in Pulmonary Arteries of Rats with Monocrotaline-Induced Pulmonary Hypertension / 实用儿科临床杂志

Objective To examine the expression of typeⅠcollagen in pulmonary arteries of rats with monocrotaline(MCT)-induced pulmonary hypertension(PH) and explore the mechanism of pulmonary vascular structural remodeling.Methods Twelve male Wistar rats were randomly divided into 2 groups: the MCT group(n=6) and the control group(n=6),which received a single intraperitoneal injection of MCT solution(60 mg?kg-1,the first day) or 9 g?L-1saline,respectively.After 3 weeks,mean of pulmonary artery pressure(mPAP),the value of right ventricle/(left ventricle plus septum)[RV/(LV+S)] and body weight were measured.Lung sections(HE stained) were observed under lightmicroscope for changes of the pulmonary arteries.The protein expression of typeⅠcollagen in pulmonary arteries was detected by immunohistochemical technique.Results Three weeks after MCT injection,compared with control group,mPAP and RV/(LV+S) increased significantly in MCT group[mPAP:(10.60?2.06) mmHg(1 mmHg=0.133 kPa) vs(32.40?3.24) mmHg,P