Effects of NaHS on MBP and learning and memory in hippocampus of mice with spinocerebellar ataxia / 中国应用生理学杂志

To investigate the effects of exogenous NaHS on myelin basic protein (MBP) and learning and memory of hippocampal neurons in mice with spinocerebellar ataxia type 3 (SCA3) and its therapeutic significance. Twelve male normal mice were randomly selected as normal control group (NC Group), and 48 SCA3 mice were randomly selected as SCA3 model group (M Group), low dose group (NL Group, 10 μmol/kg), medium dose group (NM Group, 50μmol/kg) and high dose group (NH Group, 100 μmol/kg), 12 rats in each group. The drug treated groups were injected with NaHS intraperitoneally once a day for 4 weeks. The changes of learning and memory ability of SCA3 mice before and after the intervention of different doses of NaHS were determined by Morris water maze, the content of hydrogen sulfide (HS) in hippocampus was measured by spectrophotometry, the expression of MBP was detected by immunohistochemistry, and the morphological changes of neuron myelin sheath were observed by electron microscope. Compared with the control group, the learning and memory ability of SCA3 mice was decreased significantly (P＜0.05), and the content of HS in hippocampus was decreased (P＜0.05). After different doses of exogenous NaHS treatment, the learning and memory ability was improved in different degrees (P＜0.05), and the contents of HS and MBP in hippocampus of SCA3 mice were also improved in different degrees (P＜0.05). Exogenous NaHS may increase the contents of HS and MBP in the hippocampus of SCA3 mice, which may have a protective effect on the neurons, and then improve the learning and memory ability of SCA3 mice, and provide a new idea for the treatment of SCA3.

Effect of H2 S system on space learning and memory ability in PTSD model rat and on the frequency of spontaneous discharges of hippocampus neurons / 中国药理学通报

Aim To explore the behavior and CBS /H2 S levels of hippocampus in post traumatic stress dis-order (PTSD)rats and study the effect of exogenous H2 S on PTSD rats.Methods Single prolonged stress paradigm was adopted to prepare PTSD animal model. Morris water maze test was adopted to test space learn-ing and memory ability.CBS /H2 S content in hippo-campus tissue sample was measured using Western blot and methylene blue method.In vivo extracellular single unit recording was used to examine the frequency of spontaneous discharges of hippocampus neurons.Re-sults ① Escape latency increased and quadrant time (%)and platform crossing times decreased in Morris water maze test of PTSD group compared with normal group(P <0.01 ).CBS /H2 S level in hippocampus tis-sue of PTSD group also decreased compared with nor-mal group (P <0.01 ,P <0.05 ).② Escape latency decreased and quadrant time(%)and platform cross-ing times increased in Morris water maze test of NaHS+PTSD group compared with PTSD group(P <0.01 ).③ L-cysteine increased the frequency of spontaneous discharges of hippocampus neurons(P < 0.01 ).Con-clusions Learning and memory ability decrease in PTSD model rats owing to the inhibition of CBS /H2 S content in hippocampus tissue.The mechanism of be-havior improvement of H2 S on PTSD model rat is possi-bly related to the excitation of H2 S on frequency of spontaneous discharges of hippocampus neurons.

H2 S regulates severe acute pancreatitis through PI3K/AKT-NF-κB pathway / 重庆医学

Objective To explore the role and mechanism of H2 S in severe acute pancreatitis .Methods SD rats were randomly assigned into several experimental groups :contorl group(n=6) ,SAP group(n=10) ,PAG+SAP group(n=10) ,5 mg/kg NaHS+SAP group(n=10) ,10 mg/kg NaHS+SAP group(n=10) ,20 mg/kg NaHS+SAP group(n=10) ,100 mg/kg NaHS+SAP group (n=10) ,wortmannin(W)+ SAP group(n= 10) ,5 mg/kg NaHS + W+ SAP group(n=10) and 100 mg/kg NaHS+ W+ SAP group(n=10) .These rats were intra-peritoneal injected L-Arginine to get SAP model ,and sacrificed ar 24 h hour after the first in-jection .Plasma IL-6 and MPO activity in pancreas were determined by ELISA .Expression of p-AKT and IκBαin pancreas were de-tected by Western blot ,and NF-κB activity was assessed with EMSA .Results SAP and PAG+ SAP resulted in a significant in-creasing in plasma IL-6 ,MPO activity and expression of p-AKT in pancreas ,when compared with the control group(P<0 .05) ,and NF-κB activity also increased ,and NF-κB activity in PAG+SAP group was more significant (P<0 .05);however ,IκBαexpression in SAP and PAG+SAP down-regulated obviously ,when compared with the control group(P<0 .05) ,and the expression in PAG+SAP group was significantly lower(P<0 .05) .Different dosage of NaHS reduced that the level of plasma IL-6 ,MPO activity ,ex-pression of p-AKT and NF-κB activity in pancreas changed in different degrees ,yet IκBαexpression in these groups increased gradu-ally .When compared with the SAP group ,5 mg/kg NaHS+SAP and 100 mg/kg NaHS+SAP ,plasma IL-6 ,MPO activity and ex-pression of p-AKT in pancreas significantly depressed after given wortmannin ,besides NF-κB activity also down-regualated;never-theless IκBαexpression up-regulated .Conclusion H2 S in precondition induced the development of an anti-inflammatory activity in SAP ,and in proportion with the concentration of H2 S in blood in a degree .H2 S regulated the degree of SAP injury via PI3K/AKT-NF-κB pathway .

The Inhibitory Effects of Hydrogen Sulfide on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

In this study, we studied whether hydrogen sulfide (H2S) has an effect on the pacemaker activity of interstitial cells of Cajal (ICC), in the small intestine of mice. The actions of H2S on pacemaker activity were investigated using whole-cell patch-clamp technique, intracellular Ca2+ analysis at 30degrees C and RT-PCR in cultured mouse intestinal ICC. Exogenously applied sodium hydrogen sulfide (NaHS), a donor of hydrogen sulfide, caused a slight tonic inward current on pacemaker activity in ICC at low concentrations (50 and 100 micrometer), but at high concentration (500 micrometer and 1 mM) it seemed to cause light tonic inward currents and then inhibited pacemaker amplitude and pacemaker frequency, and also an increase in the resting currents in the outward direction. Glibenclamide or other potassium channel blockers (TEA, BaCl2, apamin or 4-aminopydirine) did not have an effect on NaHS-induced action in ICC. The exogenous application of carbonilcyanide p-triflouromethoxyphenylhydrazone (FCCP) and thapsigargin also inhibited the pacemaker activity of ICC as NaHS. Also, we found NaHS inhibited the spontaneous intracellular Ca2+ ([Ca2+]i) oscillations in cultured ICC. In doing an RT-PCR experiment, we found that ICC enriched population lacked mRNA for both CSE and CBS, but was prominently detected in unsorted muscle. In conclusion, H2S inhibited the pacemaker activity of ICC by modulating intracellular Ca2+. These results can serve as evidence of the physiological action of H2S as acting on the ICC in gastrointestinal (GI) motility.

The role of hydrogen sulfide in adriamycin-induced dilated cardiomyopathy in rats / 中国药理学通报

Aim To investigate the effect of hydrogen sulfide(H2S) on apoptosis of myocardial tissues of adriamycin-induced dilated cardiomyopathy in rats and to explore the underlying mechanisms.Methods Weight-matched male Wistar rats were randomly divided into 5 groups as follows:(1) ADR group(n=12),2.5 mg?kg-1 of adriamycin was injected intraperitoneally once a week for 10 weeks(total dose of 25 mg?kg-1);(2) ADR+small-dose-NaHS group(n=12),the dosage and use of adriamycin were as mentioned above,while NaHS solution was injected to rats at a dosage of 2.8 ?mol?kg-1?d-1 at the same time;(3) ADR+large-dose-NaHS group(n=12),the dosage and use of adriamycin were as mentioned above,while NaHS solution was injected to rats at a dosage of 14 ?mol?kg-1?d-1 at the same time;(4) ADR+PPG group(n=12),in which the dosage and use of adriamycin were as mentioned above,while PPG solution was injected to rats at a dosage of 30 mg?kg-1?d-1;(5) control group(n=9),an equivalent volume of physiological saline was administered weekly for 10 weeks.(6) NaHS group(n= 9),14 ?mol?kg-1 of NaHS solution was injected to rats intraperitoneally for 10 weeks.Hemodynamic and echocardiographic measurements were obtained 10 weeks after treatment.Histological examination was implemented at the 10th week after sacrificed.And apoptotic index,Fas and Bcl-2 expressions in myocardiocytes were analyzed semiquantitatively by TUNEL or immunohistochemical analysis.Meanwhile,H2S concentrations in serum and myocardial tissues were evaluated by a modified sulfide electrode-based method.Results Left ventricular systolic pressure(LVSP),difference of left ventricular pressure(△LVP=left ventricular systolic pressure minus left ventricular diastolic pressure) and ventricular peak rate of contraction(+LV dp/dtmax),peak rate of relaxation(-LV dp/dtmax) were significantly reduced in the group of ADR rats(P0.05).Conclusion H2S might play an important role in the development of adriamycin-induced dilated cardiomyopathy.Administration of exogenous H2S could protect the cardiac function and myocardial pathological lesions via the down-regulation of augmented myocardiocyte apoptosis.

Protective effects of hydrogen sulfide on rats with multiple organ dysfunction syndrome / 西安交通大学学报(医学版)

Objective To investigate the possible protective effects of hydrogen sulfide (H2S) on rats with multiple organ dysfunction syndrome (MODS). Methods NaHS was taken as a donor of H2S. Forty Sprague-Dawley rats were divided into 5 groups with 8 rats in each group:sham group,MODS 12 h model group,MODS 24 h model group,NaHS protection 12 h and 24 h groups. The content of superoxidase dismutase (SOD),malondialdehyde (MDA),glutathione peroxidase (GSH-Px),alanime transaminse (ALT),creatine kinase (CK) and creatinine (Cr) in serum were measured,respectively. The histopathological changes in the heart,liver,lung,kidney and small intestine were observed. Results The serum content of SOD and GSH-Px was significantly higher in protected H2S groups (P