Renal interstitial fibrosis induced by high-dose mesoporous silica nanoparticles via the NF-κB signaling pathway.

Previous studies have indicated that the nephrotoxicity induced by mesoporous silica nanoparticles (MSNs) is closely related to inflammation. Nuclear factor kappa B (NF-κB), a common rapid transcription factor associated with inflammation, plays an important role in the process of many kidney diseases. Acute toxicity assessment with a high-dose exposure is critical for the development of nanoparticle, as a part of standardized procedures for the evaluation of their toxicity. The present study was undertaken to observe the acute toxicity, predict the potential target organs of MSNs injury, and test the hypothesis that the NF-κB pathway plays a role in mediating the acute kidney injury and renal interstitial fibrosis in mice induced by MSNs. Balb/c mice were intraperitoneally injected with MSNs at concentrations of 150, 300, or 600 mg/kg. All of the animals were euthanized 2 and 12 days after exposure, and the blood and kidney tissues were collected for further studies. In vitro, the cytotoxicity, fibrosis markers, and NF-κB pathway were measured in a normal rat kidney cell line (NRK-52E). Acute kidney injury was induced by MSNs in mice after 2 days, some renal tubules regenerated and renal interstitial fibrosis was also observed. The expression of fibrosis markers and the nuclear translocation of NF-κB p65 in the kidney homogenates increased after exposure to MSNs. The in vitro study showed that MSNs cause cytotoxicity in NRK-52E cells and increased the expression of fibrosis markers. In addition, the NF-κB pathway could be induced, and inhibition of the NF-κB pathway could alleviate the fibrosis caused by MSNs. We conclude that inflammation is a major effector of the acute kidney toxicity induced by MSNs and results in renal interstitial fibrosis, which is mediated by the NF-κB signaling pathway.

Improving the dissolution rate of poorly water-soluble resveratrol by the ordered mesoporous silica / 药学学报

The aim of this study is to synthesize the ordered mesoporous silica (OMS) as drug carrier to improve release property of insoluble drug and investigate the dissolution profile of insoluble drug from the porous carrier. The OMS was obtained by using cetyltrimethyl ammonium bromide as the template and resveratrol was selected as the model drug. The resveratrol-loaded OMS (Res-OMS) were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 adsorption-desorption, X-ray diffraction (XRD) and FT-IR spectroscopy. In vitro drug release behavior was also investigated. It was found that the synthesized OMS showed a large surface area, a narrow pore size distribution and an important mesoporosity associated to hexagonally organized channels. Compared with physical mixture and crystalline powder, resveratrol was in amorphous or molecular form after loading into OMS. The release rate ofresveratrol from drug-loaded OMS was significantly increased suggesting the great potential application of OMS for the formulation of poorly soluble drugs.

The intervention effect of tanshinone on electrophysiological abnormality of hypertrophic myocardium / 中华急诊医学杂志

Objective To study the intervention effect of tanshinone on electrophysiological abnormality of hypertrophic cardicoyte in order to illuminate the underlying mechanism of tanshinone in preventing the arrhythmia induced by myocardial hypertrophy. Method Twenty-week-rid SD rats (200～250 g) were divided into 4 groups (8 in each group) randomly. Of 4 groups, rats of three groups were operated on by a procedure of 'one kidney one clamp' to make renal artery constriction. The rest group served as sham operation group (control group). When the blood pressure increased,rats of operation groups were divided into tanshinone group, captopril group and hyper-trophic group. The effects of tanshinoe and captopril were observed and compared on the action potential duration (APD),L-type calcium current (ICa, L) and transient outward potassium current (Ito) density in cellular membrane of hypertrophic myocardium by using patch clamp and intra-cellular calcium survey technique. Results The blood pressure in operation groups was obviously higher than that in sham-operation group (P<0.01), but there was no difference between operation groups (P>0.05). The ratio of ventricle weight to body weight (VW/BW) was much higher in hypertrophic group than in control group (P<0.01), and it significantly decreased after interven-tion with tanshinone or captopril (P<0.01). Compared with hypertrophic group, tanshinone markedly shortened the prolongation of action potential duration (P<0.01), decreased membrane capacity and peak amplitude of ICa,L(P<0.01), but had no effect on the density of ICa,L. Tanshinone also significantly increased Ito current density and peak amplitude, which were completely different from hypertrophic group (P<0.05). There were similar results foundin captopril intervention. Conclusions Tanshinone could reduce calcium influx and resume the activity of ho ion channels, and thus shorten the first phase and the plateau phase of repolarization and decrease the prolongation of APD in hypertrophic cadiocyte. So tanshinone can prevent the onset of arrhythmia attributed to the myocardial hypertrophy.