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>

H(2)S protects myocardium against ischemia/reperfusion injury and its effect on c-Fos protein expression in rats / 生理学报

<p><b>UNLABELLED</b>The present study was aimed to study the effect of hydrogen sulfide (H(2)S) on rat myocardial ischemia/reperfusion (I/R) injury and whether the effect is mediated by c-Fos protein expression. Male Sprague-Dawley rats were randomly divided into 4 groups:</p><p><b>CONTROL GROUP</b>sham treatment; I/R group: the rat anterior descending branch of left coronary artery was occluded for 30 min and then released to allow reperfusion for 60 min; NaHS (exogenous H(2)S donor) groups: the rats were pretreated with NaHS at 2.8 μmol/kg body weight and 14 μmol/kg body weight (i.v.), respectively, before I/R treatment. Hemodynamics (LVSP, LV±dp/dt(max)) and electrocardiogram (ECG, lead II) were monitored continuously with multi-channel physiological signal analysis system after reperfusion. Myocardial infarct size was measured using triphenyltetrazolium chloride (TTC) staining. H(2)S concentration in the plasma was determined with a spectrophotometer. Morphological and ultrastructural changes in myocardial tissue were evaluated by HE staining and by a transmission electron microscope. The evaluation of c-Fos protein expression in myocardial tissue was performed by immunohistological staining. The results showed that H(2)S concentration in rat plasma in I/R group was significantly decreased compared with that in the control group [(30.32±5.26) vs (58.28±7.86) μmol/L, P<0.05]. NaHS at 2.8 and 14 μmol/kg body weight reduced the changes in LVSP, LV±dp/dt(max) in rat myocardium induced by I/R injury. The values of LVSP, +dp/dt(max) and -dp/dt(max) at 60 min during myocardial reperfusion were enhanced from (75.93±1.10)%, (66.27±4.78)% and (66.01±4.79)% in I/R group to (84.34±2.24)%, (76.38±1.93)% and (75.47±5.29)% in 2.8 μmol/kg body weight NaHS group (P<0.05, P<0.01, n=6), (88.40±2.88)%, (80.10±2.09)% and (80.48±6.20)% in 14 μmol/kg body weight NaHS group (P<0.01, n=6), respectively. Compared with that in 2.8 μmol/kg body weight NaHS group, the enhancing effect was more prominent in 14 μmol/kg body weight NaHS group. NaHS at 14 μmol/kg body weight markedly alleviated the injury in morphological changes and decreased c-Fos protein expression in myocardial tissue compared with that in I/R group (0.20±0.06 vs 0.32±0.10, P<0.05). These results suggest that H(2)S protects myocardium against I/R injury and this protective effect may be related to the down-regulation of c-Fos protein expression.</p>