Effects of nitronyl nitroxide on myocardial hypoxia and apoptosis-associated proteins in hypobaric hypoxia mice / 中国药学杂志

OBJECTIVE: To investigate the effects of nitronyl nitroxide(HPN) on the myocardial hypoxia- and the expression of apoptosis-associated proteins in hypobaric hypoxia condition mice. METHODS: Sixty BALB/c mice were divided into normal control group, hypoxia model group, acetazolamide group and HPN group randomly. After single intraperitoneal injection of HPN for 30 min, the mice were exposed to a simulated high altitude of 8 000 m for 12 h. After hypoxic exposure, mice were sacrificed and the content of lactate(LD) and lactate dehydrogenase(LDH) activity in heart were determined. HIF-1, VEGF, caspase-3, Bax and Bcl-2 were detected by immunohistochemistry. RESULTS: Compared with normal control group, the LD level and LDH activity in hypoxia model group increased significantly. In addition, the expression of HIF-1α, VEGF, caspase-3 and Bax were increased, Bcl-2 and Bc1-2/Bax ratio was decreased. Pre-treated with HNP the LD level and LDH activity, the expression of HIF-1α, VEGF, caspase-3 and Bax were decreased effectively, the expression of Bcl-2 and Bc1-2/Bax ratio was increased. CONCLUSION: HPN has protective effect on heart injury induced by hypobaric hypoxia in mice. Its mechanism may be related to the amelioration of energy metabolism, alleviation of oxidative stress as well as inhibition of myocardial apoptosis.

Protective effect and action mechanism of petroleum ether extracts from Saussurea involucrate on brain tissues of hypoxia rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the protective effect and action mechanism of petroleum ether extracts from Saussurea involucrate on brain tissues of hypoxia rats under constant pressure and closed conditions.</p><p><b>METHOD</b>The PESI dosage-dependent experiment for hypoxia rats was conducted under constant pressure and closed conditions by intraperitoneally injecting 125, 250, 500 mg x kg(-1) to finalize that the optimum dosage is the high dose of PESI. Afterwards, 90 Wistar rats were randomly divided into the hypoxic model group, the acetazolamide 250 mg x kg(-1) group and the PESI high dose group. Each group was further divided into three subgroups according to different hypoxia times, with 10 rats in each subgroup. Under the same hypoxia and administration conditions, the rats were sacrificed after 0, 3, 6 h respectively. Their brain samples were collected for common pathological observation and immunohistochemical staining of HIF-1alpha. Real-time RT-PCR was used to detect HIF-1alpha, EPO, HO-1 and Caspase-3 gene expressions. And the Western blot assay was adopted to detect HIF-1alpha protein expression.</p><p><b>RESULT</b>The brain tissues of the hypoxia model group were severely damaged with the increase in the hypoxia time. The acetazolamide group and the PESI high does group were damaged in a much lower degree. According to the gene expression and the Western blot assay, high dose of PESI could inhibit HIF-1alpha expression. According to the pure gene expression test, high dose of PESI could increase EPO and HO-1 mRNA expressions, but inhibit Caspase-3 mRNA expression.</p><p><b>CONCLUSION</b>PESI's protective mechanism for brain tissues of hypoxia rats under constant pressure and closed conditions may be related to its effects in inhibiting HIF-1alpha expression, increasing EPO expression and resisting cell apoptosis.</p>

Liquid chromatography tandem mass/mass spectrometry for the quantification of fudosteine in human serum without precolumn derivatization

A quantitative analysis method for fudosteine in human serum by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry [HPLC-ESI/MS/MS] was established, which shows high sensitivity and selectivity. The mobile phase composition was 75% 20 mM acetic acid and 25% acetonitril, which was pumped at a flow rate of 0.40 mL/ min. The overall chromatographic run time was approximately 7 min. The autosampler was set with an injection volume of 10 microL. The calibration curve was linear in the concentration range of 0.1-15.0 microg/mL. The coefficient of determination [r] was greater than 0.9998. This method has been fully validated and shown to be specific, accurate and precise. The method was simple, rapid and the sample preparation was minimal. It was successfully applied to the analysis of healthy volunteer

Synthesis and cardioprotective effect of a novel anti-ischemic/reperfused injury compound / 药学学报

The aim of present study is to investigate the cardioprotective effect of a new compound acetyl ferulaic isosorbide (AFI), composed of ferulaic acid (FA) and isosorbide mononitrate (ISMN) by esterification in myocardial ischemia/reperfusion (MI/R). Male Sprague-Dawley rats, subjected to 30 minutes of myocardial ischemia and 3 hours of reperfusion, randomly received one of the following treatments separately: SHAM, I/R (MI/R + solvent), SF (MI/R+SF, 40 mg x kg(-1), ig), ISMN (MI/R + ISMN, 30 mg x kg(-1), ig), SF + ISMN (MI/R + SF + ISMN, 40 mg x kg(-1) + 30 mg x kg(-1), ig) and AFI (MI/R + AFI, 10 mg x kg(-1), ig). Left ventricle developed pressures (LVDP) and the maximal first derivative of developed pressure ( +/-dP / dtmax) were monitored throughout the experiments. Myocardial infarction size, serum creatine kinase (CK) activity, lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, hydrogen peroxide (H2O2), malondialdehyde (MDA) and nitric oxide (NO) production were determined at the end of reperfusion. Compared with SF, ISMN or SF + ISMN treatment groups, AFI treatment decreased infarction size (n=8, P < 0.01), improved cardiac function as evidenced by increased LVDP and +/- dP/dtmax (n=8, P < 0.05), increased serum SOD activity, reduced serum CK and LDH activities, H2O2 and MDA production (n=8, P < 0.05). The new compound AFI showed a stronger cardioprotective effect against MI/R injury than SF, ISMN or their combined administration did.