Puerarin-loaded ultrasound microbubble contrast agent used as sonodynamic therapy for diabetic cardiomyopathy rats.

In this study, a puerarin-loaded ultrasound sulfur hexafluoride microbubble contrast agent as a sonodynamic therapy (SDT) was developed to improve targeted drug delivery and pharmacodynamic effects in diabetic cardiomyopathy (DCM) treatment. Fluorescence microscope morphology was applied to confirm the fabrication of the puerarin - microbubbles (PMBs). The average size distribution and zeta potential of PMBs were 760.0 ± 101.2 nm and -20.4 ± 6.59 mV, respectively. In vitro and in vivo experiments were carried out to study the pharmacodynamic effects and targeted drug delivery of PMBs. The cytotoxicity, assessed by the cell viability of human umbilical vein endothelial cells (HUVECs), showed that the microbubbles were nontoxic even in high concentration of 2.500 mg/mL, and the wound healing scratch assay proved that PMBs cloud obviously improve the migration ability of HUVECs. Furthermore, streptozotocin (STZ) accompanied with high-energy diets was employed to build the DCM rat model. The blood glucose, histological changes of the pancreas and heart, and cardiac function were used to confirm the obtainment of the DCM rat model. Histological and physiological changes of the PMBs treatment group indicated that PMBs had a significant therapeutic efficacy when compared to the DCM model group. Therefore, PMBs are a promising strategy for a targeted drug delivery system and a novel noninvasive treatment for DCM.

Inhibition Effect of Non Custodial Terpenes-3β-Alcohol to Autoimmune Encephalomyelitis / 天津医药

Objective To study the inhibition effect of non custodial terpenes-3β-alcohol to experimentally in-duced autoimmune encephalomyelitis in guinea pigs. Methods Different doses (25 mg/kg, 50 mg/kg and 100 mg/kg) of non custodial terpenes-3β-alcohol were given to the experimentally induced autoimmune encephalomyelitis model of guinea pigs by gavage for 8 weeks. Plasma levels of CD4+/CD8+, IL-1, IL-2, IL-6, IL-10, neuropeptide Y (NPY), beta endorphin (β-EP) , transforming growth factor-β(TGF-β), matrix metalloproteinase (MMP-2), nitric oxide synthase (NOS) and leuko-cyte differentiation antigen CD3 were assessed. The brain neuron morphology changes was observed under light microscopy while its ultrastructure changes was observed under electron microscope. NOS expression in neurons was observed through immunofluoresce technology. Results Non custodialterpenes-3β-alcohol inhibited the increase of plasma CD4+/CD8+, IL-1, IL-2, IL-6, IL-10, MMP-2, CD3 and NPY while decrease of plasmaβ-EP, brain TGF-β. It also increase NOS expres-sion in neuronal cytoplasm and maintained neuron morphology. Conclusion Non custodial terpenes-3β-alcohol inhibit-ed the experimental autoimmune encephalomyelitis in guinea pig.

Exogenous ATP induces formation of membrane pore in PC12 cells / 中国病理生理杂志

AIM:To investigate the formation of membrane pore in PC 12 cells induced by exogenous adenosine triphosphate ( ATP) and to identify the key molecular targets .METHODS:PC12 cells were treated with different concen-trations of ATP to establish the injury model .The morphological change was observed under an inverted phase -contrast mi-croscope.The viability of the PC12 cells was measured by CCK-8 assay.Fluorescent dye YO-PRO-1 was used to detect the membrane permeability.The expression of P2X7 receptor and pannexin 1 (Panx1) at mRNA and protein levels was as-sessed by real-time PCR and Western blotting .RESULTS:After exposed to ATP (1 mmol/L, 3 mmol/L and 5 mmol/L) for 3 h, the PC12 cells became edematous , and the number of adherent cells decreased gradually in a dose-dependent man-ner .The cell viabilities in 3 mmol/L ATP group and 5 mmol/L ATP group were significantly decreased compared with con-trol group (P0. 05).The expression of P2X7 receptor at mRNA and protein levels was significantly increased (P0.05) when PC12 cells were exposed to ATP for 3 h.CONCLUSION:Extracellular ATP at high concentration may induce membrane pore formation with the expression and activation of P 2X7 receptor in PC12 cells.

Study of Damaging Effect of Exogenous Advanced Glycation End Products on Vascular Endothelial Cell in Vitro / 天津医药

Objective: To explore the mechanism of damaging effect of advanced glycation end products (AGEs) on human umbilical vein endothelial cell (HUVEC) in vitro. Methods: The HUVEC was incubated with exogenous AGEs for 12 h, and ergamine (Hi) and catalase (CAT) were used as control. The activity, monolayer permeability, apoptosis rate, biochemical indexes and morphous changes were detected in HUVEC. Results: The activities of HUVEC were dose-dependently reduced by exogenous AGEs(40 mg/L, 120 mg/L and 160 mg/L), meanwhile the monolayer permeability, the malondialdehyde (MDA) content and apoptosis rate were increased，the activity of superoxide dismutase（SOD）was decreased（P < 0.05, respectively). There was no significant difference in damaging effect between exogenous AGEs and Hi(P ＞ 0.05). The damaging effect of exogenous AGEs was obviously inhibited by CAT in HUVEC. Conclusion: Exogenous AGEs induced the damaging effect on vascular endothelial cells, which may be related to the oxidative stress.