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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.
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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.
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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
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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
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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