Multiple hemodynamic effects of endogenous hydrogen sulfide on central nervous system in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Endogenous hydrogen sulfide is a new neuromodulator which takes part in the regulation of central nervous system physiology and diseases. Whether endogenous hydrogen sulfide in the central nervous system regulates cardiovascular activity is not known. In the present study, we observed the hemodynamic changes of hydrogen sulfide or its precursor by intracerebroventricular injection, and investigate the possible roles of endogenous digitalis like factors and sympathetic activity in the regulation.</p><p><b>METHODS</b>Ninety-four Sprague-Dawley rats underwent a right cerebroventricular puncture, then the hydrogen sulfide saturation buffer or its precursor injected by intrcerebroventricular catheter. A heperin-filled catheter was inserted into the right femoral artery or into the left ventricle, and changes of blood pressure or cardiac function recorded by a Powerlab/4S instrument. Phentolamine or metoprolol were pre-injected to observe the possible role in autonomic nerve activity. After rats were sacrificed, plasma was collected and endogenous digitalis-like factors were measured with a commercial radioimmunoassay kit. The aortic, cardiac sarcolemmal vesicles were isolated and the activity of Na(+)-K(+)-ATPase was measured as ouabain-sensitive ATP hydrolysis under maximal velocity conditions by measuring the release of inorganic phosphate from ATP. Unpaired Student's t test for two groups or analysis of variances (ANOVA) for multiple groups were used to compare the differences of the changes.</p><p><b>RESULTS</b>Intracerebroventricular injection of hydrogen sulfide induced a transient hypotension, then dramatic hypertenive effects in a dose-dependent manner. Bolus injection of L-cysteine or beta- mercaptopyruvate also increased mean arterial pressure (P < 0.01), whereas hydroxylamine-a cystathionine beta synthase inhibitor decreased the arterial pressure (P < 0.01). Hydrogen sulfide and L-cysteine increased mean arterial pressure, left ventricular develop pressure and left-ventricle maximal rate of systolic and diastolic pressure; these functions were decreased by hydroxylamine (P < 0.01). Glibenclamide (a K(ATP) channel blocker) blocked the transient hypotensive effect, phentolamine (an alpha-adrenergic receptor blocker) blocked the hypertensive effect, and metoprolol (a selective beta 1 receptor blocker) blocked the positive inoptropic effect of central nervous system hydrogen sulfide. The endogenous digitalis-like factors in plasma were elevated (P < 0.01) after treatment with L-cysteine, association with decreasing Na(+)-K(+)-ATPase activity in cardiac or aortic sarcolemmal vesicles (P < 0.01). Hydroxylamine injection reduced the endogenous digitalis-like factors level in plasma association with increasing Na(+)-K(+)-ATPase activity in cardiac and aortic sarcolemmal vesicles.</p><p><b>CONCLUSION</b>Central nervous system endogenous hydrogen sulfide upregulated mean arterial pressure and cardiac systolic function by activation of sympathetic nerves or release of endogenous digitalis-like factors.</p>

Protective effect of tert-butylhydroquinone on bone marrow cells in rats from cytotoxicity induced by benzene in vitro / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of tert-butylhydroquinone on bone marrow cells in rats from cytotoxicity induced by benzene in vitro.</p><p><b>METHODS</b>The bone marrow cells in rats were divided into two groups randomizedly. Cells of the control group were stimulated by 0, 5, 10, 15, 20 mmol/L benzene for 2, 4, 6 hours respectively. Cells of the tBHQ-pretreated group were treated by 100 micromol/L tBHQ for 12 hours followed by the same conditions as the control group. The DNA damage was detected by single cell gel electrophoresis assay (SCGE) and cell apoptosis was examined by flow cytometry. The activities of NAD (P) H: quinone oxidoreductase (NQO1) in bone marrow cells of rats were also measured before benzene treatment in two groups.</p><p><b>RESULTS</b>In control group, the DNA damage and the apoptosis of bone marrow cells was increased with the growing concentration and time of benzene treatment. The DNA migration and the lengths of DNA migration of the bone marrow cells in the rats under 5, 10, 15, 20 mmol/L benzene treatment in the tBHQ-pretreated group were significantly lower than those in control group at the same time point (P < 0.05). The apoptosis of the bone marrow cells in the rats stimulated by 15, 20 mmol/L benzene for 2 hours and 10, 15, 20 mmol/L benzene for 4 hours as well as 5, 10, 15, 20 mmol/L benzene for 6 hours were also significantly lower than those in control group (P < 0.05). The activities of NQO1 in the bone marrow cells in the rats were increased after tBHQ treatment (P < 0.01) (1.62 +/- 0.16 min(-1).mg(-1) vs. the control group: 0.95 +/- 0.08 min(-1).mg(-1)).</p><p><b>CONCLUSION</b>The benzene can induce the DNA damage and the apoptosis of bone marrow cells in rats in a time dependent and dose dependent manner to some extent. The tBHQ can protect the bone marrow cells in rats from the cytotoxicity induced by benzene, which can be partly explained by the increase of the NQO1 activity induced by tBHQ.</p>

Mechanism of improving effect of losartan on insulin sensitivity of non-insulin-dependent diabetes mellitus rats / 生理学报

The specific inhibition of angiotensin II action at AT(1) receptors by losartan has been shown to decrease peripheral insulin resistance in type 2 diabetic patients and animal models. We examined the effect of losartan on the expression of insulin receptor substrate 1 (IRS-1), protein kinase B (PKB) and glucose transporter 4 (GLUT4), as well as the phosphorylation status of IRS-1 and the association between IRS-1 and phosphatidylinositol (PI) 3-kinase in skeletal muscle from fat-fed and-streptozotocin (STZ)-treated rats, an animal model of type 2 diabetes mellitus. In addition, the effects of losartan on GLUT4 translocation in muscle cells and on insulin sensitivity were also evaluated. Muscle tissues were isolated from male losartan-treated and untreated normal or non-insulin-dependent diabetes mellitus (NIDDM) rats with a dose of 4 mg/kg per day for 6 weeks. Oral administration of losartan improved insulin sensitivity, which was determined by an oral glucose tolerance test (OGTT). In skeletal muscles, the protein levels of IRS-1, PKB and GLUT4 in NIDDM rats were not significantly different from those of the control rats, and they were not affected by losartan. The levels of IRS-1 tyrosine phosphorylation, PI 3-kinase activity associated with IRS-1 and PKB activation after stimulation with insulin in muscle tissue of NIDDM rats were significantly decreased (P<0.01) compared with those in the control rats, while they were not increased by losartan. Losartan had a major effect on GLUT4 translocation in myocytes, as it significantly increased (P<0.05) the insulin-induced amounts of GLUT4 in plasma membrane (PM) and T-tubules (TT) in myocytes from NIDDM rats. Consistent with these results, the plasma glucose level in losartan-treated NIDDM rats was decreased (P<0.05) compared with that in untreated NIDDM rats. Our results suggest that losartan may exert beneficial effects on insulin resistance by increasing the translocation of GLUT4 in muscle tissue, which is probably associated with a non-PI 3-kinase-dependent mechanism.

Changes of VASP in shear stress induced cytoskeleton reorganization in endothelial cells / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of different level of laminar shear stresses on the vasodilator-stimulated phosphoprotein (VASP) location and expression changes associated with actin reorganization and it's mechanism.</p><p><b>METHODS</b>A parallel-plate flow chamber device was used to create laminar shear stress in vitro on cultured human umbilical endothelial cells (HUVECs). The distribution of VASP and microfilament were observed by double immunofluorescence staining. RT-PCR was used to test VASP mRNA level, while VASP parameters were analyzed quantitatively with Western blot.</p><p><b>RESULTS</b>After exposure to a flow of 10 dyn/cm2 flow for 24 h, HUVECs were elongated and oriented gradually to the direction of the flow. The microfilaments were recruited and oriented to the direction of flow with thicker VASP, specially targeted to the ends of stress fibres. RT-PCR result indicated shear could induce VASP mRNA increase. Western blotting data showed a dynamic reversible phosphorylation of VASP during 24 h, and total VASP expression increased rapidly, peaked at 2 h, then recovered at 8h followed by a slow increase again. H89, a cAMP inhibitor could inhibit shear induced VASP expression increase and phosphorylation.</p><p><b>CONCLUSION</b>VASP is an potential important component which participates in the regulation of cell cytoskeleton reorganization and morphology modification induced by shear flow via a cAMP/cAK pathway.</p>

Effect of thyroid hormone on protein kinase C signal pathway in cardiac myocytes and fibroblasts of rats in vitro / 中国应用生理学杂志

<p><b>AIM</b>To study the effect of thyroid hormone on protein kinase C activity and isoprotein expressions in cardiac myocytes and fibroblasts of rats in vitro.</p><p><b>METHODS</b>Cardiac myocytes and fibroblasts were cultured according to the method of Simpson. Cells were pretreated with 1% newborn calf serum (NCS) or Angiotensin II (Ang II) for 24 hours, then Triiodothyronine (T3) was added to the culture medium and the culture was kept for another 48 hours. The protein kinase C activation were measured by PepTaga non-radioactive PKC assay, and the expressions of PKC alpha and PKC epsilon were detected by Western blot method.</p><p><b>RESULTS</b>At the condition of 1% NCS culture medium, T3 could inhibit PKC activity and PKC epsilon expression in cardiac myocytes significantly, but the expression of PKC alpha in cardiac myocytes was not influenced by T3. In cardiac fibroblasts, neither PKC activity nor PKC alpha and PKC epsilon expressions was influenced by T3. When cells were pretreated with Ang II for 24 hours, PKC activities in cardiac myocytes and fibroblasts were increased significantly, and PKC epsilon expressions in cardiac myocytes were also markedly increased. Following a T3 treatment, PKC activity and PKC epsilon expression in cardiac myocytes were markedly decreased, but PKC activity in cardiac fibroblasts was not changed.</p><p><b>CONCLUSION</b>Whether at the condition of 1% NCS medium or in a pretreatment with Ang II, thyroid hormone could inhibit the PKC activity and PKC epsilon expression in cardiac myocytes. The influence of thyroid hormone on the PKC signal pathway in cardiac myocyte may be involved in many pathophysiological progress of myocardium.</p>

The neurophysiological features of shoulder-hand syndrome after stroke / 中华物理医学与康复杂志

Objective T_O analyze the electrophysiological features of shoulder-hand syndrome(SHS)fol- lowing stroke and investigate the relationships between peripheral nerve damage and the factors causing SHS.Meth- ods Fifty-eight stroke patients were divided into an SHS group(39 patients with shoulder-hand syndrome)and a model group(19 patients without shoulder-hand syndrome).Standard sensory and motor nerve conduction studies were performed with 58 of the patients,including sensory nerve conduction velocity(SCV),amplitude of the sensory nerve action potential(SNAP),distal motor latency(DMI)and the amplitude of the compound muscle action poten- tial(CMAP)of the median nerve.A needle electromyogram(EMG)test was performed on the abductor pollicis of the affected side with both groups.Results The needle EMG showed abnormal insertion potential,fibrillation po- tential and positive sharp waves in all 39 cases of the SHS group,which was significantly higher than in the model group.The amplitude of the sensory nerve action potential(7.77?4.34 mV)and the amplitude of the compound muscle action potential(10.13?3.15 mV)were significantly lower than those of the model group.Abnormal ampli- tude was more severe in sensory nerves than in motor nerves.Conclusion Peripheral nerve damage was found in the shoulder-hand syndrome patients,and this damage was mainly the dystrophy of axonal neuropathy.The damage severity was more in sensory nerves than in motor nerves.The study could offer an useful clue of prevention and treat- ment of shoulder-hand syndrome.

Experimental study of the anti-atherogenesis effects of sodium ferulate in hyperlipidemia rabbit and its mechanisms / 中国药理学通报

AIM: To study the anti-atherogenesis action of sodium ferulate and its mechanisms. METHODS: Atherosclerotic rabbit models were duplicated by feeding high lipid forage and ECV304 were cultured with the hyperlipidemic serum. The atherosclerotic plaque area was measured. Scanning electron microscope, spectrophotometer and immunocytochemical methods were used to detected the microstructures of endothelial cell, the content of NO in suspension and the expressions of TGFβ1, bFGF on the cell surfaces. RESULTS: Sodium ferulate could decrease the plaque area, lessen the damnification of endothelial cell induced by HLS, enhance the expression of TGFβ1 and the release of NO from ECs, and reduce the expressions of bFGF in ECs, significantly. CONCLUSION: Sodium ferulate can decrease the atherosclerotic plaque area induced by hypercholesterol, which may be relate to the expression change of cytokines.