Research advances of Zaoren Anshen prescription preparations / 中国中药杂志

Zaoren Anshen prescription preparations(ZRASs), which are prepared from three traditional Chinese herb medicines, namely fried Zizyphi Spinosae Semen, Salvia Miltiorrhizae Radix et Rhizoma and vinegar-processed Schisandrae Chinensis Fructus, are a series of proprietary Chinese medicines for the treatment of insomnia, amnesia and dizzy in clinic. In recent years, pharmacodynamic effect, chemical constituents and quality control of ZRASs had been extensively studied for the purpose of ensuring their safety, efficacy and stability, and a great progress had been made. However, there is no review of the research advance of ZRASs up to date. The present review summarized the research advance of ZRASs in quality control standards, chemical constituents, pharmacodynamic effects, and chemical analysis for the first time, with the aim to provide a reference for further studies on the effective constituents and quality control of ZRASs.

Mitochondrial Oxidative Stress Enhances Vasoconstriction by Altering Calcium Homeostasis in Cerebrovascular Smooth Muscle Cells under Simulated Microgravity / 生物医学与环境科学（英文）

Objective@#Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts. Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process. To elucidate the mechanism for this condition, we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted (HU) rat cerebral arteries.@*Methods@#Three-week HU was used to simulate microgravity in rats. The contractile responses to vasoconstrictors, mitochondrial fission/fusion, Ca @*Results@#An increase of cytoplasmic Ca @*Conclusion@#The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.

Metabolites of long-time preserved-acutely isolated rat cardiomyocytes affect L-type Ca(2+) channel current / 生理学报

The variability of peak current of L-type calcium channel (I(Ca,L)) shows an increase in cardiomyocytes after 6 h of preservation when the acutely isolated cardiomyocytes are preserved in a small volume buffer solution. The mechanism of the increased variability of I(Ca,L) is not clear. In order to obtain more accurately and stably experimental data of I(Ca,L), the aim of this study was to observe the pH changes of preservation buffer solution with acutely isolated rat cardiomyocytes, and the effects of pH changes on the shape of cardiomyocytes, the function of mitochondria and the gating property of L-type calcium channel. The results indicated that the pH was kept stable in 100 mL buffer solution, but was decreased from 7.20 to 6.95 in 20 mL buffer solution during 10 h of cardiomyocyte preservation. Therefore, 100 mL or 20 mL preservation solution was used as a normal control or acidotic group, respectively. The ratio of abnormal to normal rod-shaped cardiomyocytes increased in the acidotic group after 6 h of preservation. The acidosis induced a reduction in mitochondrial membrane potential indicated by JC-1 fluorescent probe after 8 h of cardiomyocyte preservation. The acidosis also shifted the autofluorescence of NADPH from blue to green after 8 h of cardiomyocyte preservation. The above changes in mitochondrial function induced a significant decrease in the peak I(Ca,L) and a shift in the clamped voltage at peak I(Ca,L) from +10 mV to 0 mV, after 10 h of cardiomyocyte preservation. These results suggest that the best way to preserve acutely isolated cardiomyocytes is to use a larger volume buffer system. In order to get stable peak I(Ca,L), we need to not only select a normal shape of cardiomyocyte at a bright field but also a blue fluorescent myocyte at an ultraviolet excitation.

Protein kinase Cdelta is possibly involved in the transition from hypertrophy to apoptosis of myocardiocytes / 生理学报

Cardiac hypertrophy is an adaptive process to an increased hemodynamic overload. However, the adaption may lead to the fragility of myocardium facing pathological stimuli. In the present study, experiments were designed to explore the susceptibility of hypertrophic myocardiocytes to apoptotic stimuli and the role of protein kinase Cdelta (PKCdelta) during the transition from hypertrophy to apoptosis. Endothelin-1 (ET-1)-treated cardiomyocytes were used as model of cardiac hypertrophy. Angiotensin II (Ang II) was used as an apoptotic stimulus. Cell surface area was measured to determine the extent of hypertrophy. The apoptotic rate in cardiomyocytes was detected by Hoechst 33258. (1) Cell surface area was increased by 42.5% and 67.3% following 1 nmol/L and 10 nmol/L ET-1 treatment, respectively, as compared with serum-free cultured myocytes. So the mildly and moderately hypertrophic myocyte models were set up. (2) Apoptotic rates in serum-free cultured, mildly and moderately hypertrophic myocytes after Ang II treatment were (15.54+/-1.32) %, (20.65+/-1.40) % and (29.33+/-3.52) %, respectively. It is suggested that hypertrophic myocytes are more susceptive to apoptotic stimulus. (3) Rottlerin, a specific inhibitor of PKCdelta depressed apoptotic rates induced by Ang II to (15.88+/-2.25) % in mildly hypertrophic myocytes and to (15.01+/-1.37) % in moderately hypertrophic myocytes; but rottlerin did not affect apoptotic rate induced by Ang II in serum-free cultured myocytes. These results suggest that inhibition of PKCdelta can reduce Ang II-induced apoptosis of hypertrophic cardiomyocytes and that PKCdelta is possibly involved in the apoptotic process of hypertrophic cardiomyocytes.

Enhanced BK(Ca) single-channel activities in cerebrovascular smooth muscle cells of simulated microgravity rats / 生理学报

The aim of the present study was to investigate the changes in single-channel currents of large conductance calcium-activated potassium channels (BK(Ca) channels) in cerebral vascular smooth muscle cells (VSMCs) of rats after 1-week simulated microgravity. Sprague-Dawley rats were subjected to tail-suspension (SUS) to simulate cardiovascular deconditioning due to microgravity. Cytosolic calcium ([Ca(2+)](i)) was examined by laser-scanning confocal microscopy with calcium-sensitive-dye Fluo-3/AM as fluorescent probe. Single-channel currents of BK(Ca) channels were measured with cell-attached membrane patches bathed in symmetrical high potassium solution. The [Ca(2+)](i)i level was significantly higher in cerebrovascular myocytes of SUS than that of control (CON) rats. The probability of open (Po) and the mean open time (To) of BK(Ca) channels in cerebral VSMCs significantly increased in SUS as compared with CON. However, there were no significant differences in the unitary conductance and mean close time (Tc) between the two groups. The results obtained suggest that both the elevated [Ca(2+)](i) and enhanced single-channel activities of BK(Ca) channels in cerebral VSMCs might be among the electrophysiological mechanisms that mediate the increased vasoreactivity and hypertrophic change in cerebral arteries during adaptation to simulated microgravity in rats.

Independent or combined effects of endothelin-1 and prostaglandin F2alpha on cardiomyocytes / 中国应用生理学杂志

<p><b>AIM</b>To elucidate the independent or combined effects of endothelin-1 (ET-1) and prostaglandin F2alpha (PGF2alpha) on cardiomyocytes and investigate the relationship between hypertrophy and apoptosis of cardiomyocytes.</p><p><b>METHODS</b>Cultured neonatal rat cardiomyocytes were stained with FITC-conjugated phalloidin and eosin to detect the cardiomyocyte hypertrophy evidenced by increased sarcomeric structure and cell size. Cardiomyocytes were stained with Hoechst 33258 to detect apoptotic nuclei showing features of condensation and fragmentation.</p><p><b>RESULTS</b>Cardiomyocyte hypertrophy induced by ET-1 or PGF2, shown a dose dependent effect. The area of cardiomyocytes treated by 10 nmol/L or 100 nmol/L of ET-1 for 24 h increased 68% or 84% as compared with control, respectively. The area of cardiomyocytes exposed to 10 nmol/L or 100 nmol/L of PGF2alpha for 24 h increased 28% or 106% as compared with control, respectively. The ET-1 and PGF2alpha had a synergic effect on cardiomyocyte hypertrophy, but not superimposed effect. The area of cardiomyocytes increased 80%, 122%, 96%, and 199% in 10 nmol/L ET-1 plus 10 nmol/L PGF2, 10 nmol/L ET-1 plus 100 nmol/L PGF2alpha, 100 nmol/L ET-1 plus 10 nmol/L PGF2alpha, and 100 nmol/L ET-1 plus 100 nmol/L PGF2alpha group, respectively. There were no changes in apoptotic rate of cardiomyocytes treated by ET-1 or PGF2alpha alone for 48 h. The apoptotic rate of cardiomyocytes also didn't increase in ET-1 plus PGF2alpha treatment for 24 h groups, but significantly increased in ET-1 plus PGF2alpha treatment for 48 h groups. ET-1 or PGF2alpha could induce an increase in apoptotic rate of hypertrophic cardiomyocytes. There was a positive relationship between hypertrophic extent and apoptotic rate in cardiomyocytes.</p><p><b>CONCLUSION</b>The cardiomyocytes treated by ET-1 or PGF2alpha alone only show hypertrophy, but treatment of ET-1 plus PGF2alpha for 48 h induces apoptosis of cardiomyocytes.</p>