[Toxicokinetics of emodin-8-O-ß-D-glucoside in rats in vivo].

This study aims to establish an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method for the determination of emodin-8-O-ß-D-glucoside(EG) and its metabolites in plasma, and to investigate the toxicokinetics(TK) behavior of them in rats. To be specific, the TK of EG and its metabolites from the first to the last administration in the repeated dose toxicity study was determined, and the kinetic parameters were calculated. The exposure of EG prototype and metabolites in rat plasma after oral administration of different doses of EG was evaluated. The result showed that the prototype of EG and its metabolites aloe-emodin-8-O-ß-D-glucoside, emodin, aloe-emodin, and hydroxyemodin could be detected in rats after oral administration of high-, medium-, and low-dose EG. The area under the curve(AUC) of the prototype and metabolites after the first and last administration was in positive correlation with the dose. The time to the maximum concentration(T_(max)) of EG and metabolites in the three administration groups was <6 h, and the longest in vivo residence time was 12 h. The T_(max) and in vivo residence time of EG were prolonged with the increase in the dose. The metabolites emodin, aloe-emodin, and hydroxyemodin all had two peaks. Both hydroxyemodin and aloe-emodin exhibited increased plasma exposure, slow metabolism, and accumulation in vivo. In addition, aloe-emodin-8-O-ß-D-glucoside and emodin disappeared with the increase in dose, suggesting the change of the metabolic pathway of EG in vivo in the case of high-dose administration. The mechanism of high-dose EG in vivo needs to be further explored. This study preliminarily elucidates the TK behavior of EG in rats, which is expected to support clinical drug use.

[Research progress on in vitro models of cardiomyocyte injury].

Cardiovascular diseases seriously endanger human health and life. The accompanying myocardial injury has been a focus of attention in society. Chinese medicine,serving as a natural and precious reservoir for the research and development of new drugs,is advantageous in resisting myocardial injury due to its multi-component,multi-pathway,and multi-target characteristics. In recent years,with the extensive application of culture method for isolated cardiomyocytes,a cost-effective,controllable in vitro model of cardiomyocyte injury with uniform samples is becoming a key tool for mechanism research on cardiomyocyte injury and drug development.A good in vitro model can reduce experimental and manpower cost,and also accurately stimulate clinical changes to reveal the mechanism. Therefore,the selection and establishment of in vitro model are crucial for the in-depth research. This study summarized the modeling principles,evaluation indicators,and application of more than ten models reflecting different clinical conditions,such as injuries induced by hypoxia-reoxygenation,hypertrophy,oxidative stress,inflammation,internal environmental disturbance,and toxicity. Furthermore,we analyzed advantages and technical difficulties,aiming to provide a reference for in-depth research on myocardial injury mechanism and drug development.

[Efficacy and mechanism of fire needling bloodletting for lower extremity varicose veins].

OBJECTIVE: To compare the clinical effect of lower extremity varicose veins between fire needling bloodletting and operation, and to explore the possible mechanism. METHODS: A total of 60 patients were randomized into an observation group and a control group, 30 cases in each one. In the control group，the operation was adopted. The fire needling bloodletting was applied in the observation group, twice a week for 4 weeks. Before and after treatment, the venous clinical severity score (VCSS) and venous disability score (VDS) were recorded, the hemorheological indexes [blood viscosity, plasma viscosity, hematocrit, fibrinogen and erythrocyte sedimentation rate (ESR)], immune inflammatory response indexes[serum C-reactive protein (CRP), tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6)], vascular endothelial cell function indexes [the number of circulatingendothelial cell (CEC), plasma endothelin (ET-1) and NO)] and apoptosis indexes (Bcl-2, Bax and Caspase-3) were detected in the two groups. RESULTS: Compared before treatment, the scores of VCSS and VDS, hemorheological indexes, immune inflammatory response indexes and levels of plasma NO after treatment were reduced in the two groups (P<0.05). The level of serum Bax after treatment was reduced in the observation group (P<0.05). The number of CEC and levels of plasma ET-1 after treatment were increased in the two groups (P<0.05). The levels of serum Bcl-2 and Caspase-3 after treatment were increased in the observation group (P<0.05). In the observation group, the scores of VCSS and VDS, hemorheological indexes，immune inflammatory response indexes, vascular endothelial cell function indexes and level of serum Bax after treatment were lower than the control group (P<0.05), and the levels of Bcl-2 and Caspase-3 were higher than the control group (P<0.05). CONCLUSION: Fire needling bloodletting could effectively treat lower extremity varicose veins, and the mechanism may be related to the improvement of hemorheology, downregulation of immune inflammatory response, improvement of vascular endothelial cell function and inhibition of apoptosis.