摘要
Objective To explore the mechanism by which CD137 signal regulates the aging of vas-cular smooth muscle cells(VSMCs).Methods Thirty 8-week-old male C57BL/6J mice were ran-domly divided into a young group(8 weeks old)and an aged group(80 weeks old),with 30 mice in each group.After corresponding periods of feeding,the mice were euthanized,and the plasma and aortic blood vessels were isolated.In the cell experiments,normal VSMCs were divided into a control group,bleomycin(BLM)group,combined agonist group,and combined inhibitor group.The cellular senescence level of VSMCs was assessed using a cellular senescence β-galactosidase staining kit.Western blotting and PCR were employed to examine the expression of senescence-related proteins in tissues and cells,while ELISA was utilized to measure the expression of senes-cence-related inflammatory factors.Results The expression of CD137 and γ-H2AX in the aorta was significantly higher,while that of PCNA was obviously lower in the aged group than the young group(P＜0.05).The plasma level of CD137 was notably higher in the aged group than the young group(154.0±4.1 pg/ml vs 98.0±2.3 pg/ml,P＜0.05).Compared with the normal control group,there were significantly more aged VSMCs in the BLM group(P＜0.05).While,treatment of combined agonist resulted in larger amount of aged VSMCs when compared with the BLM group(P＜0.05),which was reversed by combined inhibitor treatment(P＜0.05).The levels of TNF-α,IL-6 and IL-1β were significantly elevated in the BLM group than the normal control group(P＜0.05).The combined agonist group had even higher levels of TNF-α,IL-6,and IL-1βthan the BLM group(P＜0.05),but the levels were decreased in the combined inhibitor group(P＜0.05).Compared with the normal control group,the expression of Bcl-2,γ-H2AX,P53,and P21 were significantly increased in the BLM group,combined agonist group,and combined inhibi-tor group,while that of PCNA was significantly decreased(P＜0.05).Compared with the BLM group,the expression of P53 and P21 in the combined agonist group showed an increase(P＜0.05),and the expression of P53 was significantly decreased in the combined inhibitor group(P＜0.05).Conclusion CD137 signal regulates the P53/P21 pathway to promote VSMC aging.
摘要
Traumatic intracranial hematoma progresses rapidly and may cause quick increase of intracranial pressure and even brain hernia, ultimately leading to coma or death. Therefore, traumatic intracranial hematoma needs prompt treatment, but the prerequisite of treatment is early examination and diagnosis. Due to the limited transportation and other reasons, the existing large-scale detection devices such as CT and MRI cannot be deployed on the rescue site or during patient transportation. Instead, the portable diagnosis devices have the characteristics of miniaturization and high flexibility, which is conducive to promoting early detection, assisting diagnosis and further guiding the formulation of treatment plans. At present, more and more attention has been paid to the portable diagnosis devices in the diagnosis of intracranial hematoma. The authors summarized the conventional diagnosis methods and application of portable diagnosis devices for traumatic intracranial hematoma, aiming to provide a reference for the diagnosis of traumatic intracranial hematoma.
摘要
<p><b>OBJECTIVE</b>To prepare freeze-dried long-circulation oridonin liposomes with optimized parameters.</p><p><b>METHODS</b>Ethanol injection method followed by freeze-drying was used to prepare the liposomes. Sephadex column was used to purify liposomes. Effects of formulation factors on entrapment efficiency of long-circulation oridonin liposomes were studied. The particle size, distribution and in vitro release were determined. Pharmacokinetics of oridonin liposomes in rats was determined by HPLC and the pharmacokinetic parameters calculated by Kinetica(TM) software were compared with conventional oridonin liposomes and solution.</p><p><b>RESULTS</b>The optimized lipid formulation for long-circulation liposomes was composed of soy lecithin, cholesterol and DSPE-PEG 2000 with a ratio of 1:0.5:1.8(w/w). The ratio of drug to lipid was 1:6. Freeze-drying protectant was a mixture of glucose and mannitol (3:1). The entrapment efficiency (EE) of long-circulation oridonin liposomes was about 65%. The particle size of liposomes after hydrolyzation was 164 nm with good DPI. The liposomes showed a sustained drug release in vitro. Intravenous injected oridonin fitted with two-compartment pharmacokinetic model. The MRT of long-circulation liposomes was 2 times and 6 times and AUC was about 2 times and 3 times of conventional liposomes and oridonin solution, respectively.</p><p><b>CONCLUSION</b>Freeze-dried liposomes with high EE have been obtained by the proposed approach. This long-circulation liposomes extend oridonin half time and significantly increase AUC in rats.</p>