RESUMO
<p><b>OBJECTIVE</b>To cultivate human umbilical vein endothelial cells (HUVECs) in the serum of overfatigue rats with the intervention of Tongxinluo superfine powder (TXLSP). By examining the variation of the activity of JNK/c-Jun/HO-1 pathway, the possible mechanisms of vascular endothelial dysfunction under overfatigue conditions and the intervening effect of TXLSP were explored.</p><p><b>METHODS</b>The HUVECs were randomly divided into the normal control group, the model group, the SP600125 (a specific antagonist of JNK) group, the TXLSP group and the TXLSP + SP600125 group. The content of carboyhemoglobin (COHb) and the leak rate of lactic dehydrogenase (LDH) in different groups were measured. The mRNA and protein expression of JNK, c-Jun, HO-1 and the phosphorylation level of c-Jun (P-c-Jun) were detected using Western blot and PCR methods.</p><p><b>RESULTS</b>Compared with the normal control group, the COHb level in supernatant was increased significantly in the model group, and the expression of HO-1, JNK, c-Jun mRNA and corresponding proteins and P-c-Jun were also increased remarkably. The increases in these parameters were significantly decreased by SP600125. TXLSP showed remarkable up-regulation on the expression of JNK, c-Jun, P-c-Jun and HO-1 mRNA and their protein expression. Compared with the SP600125 group, the expressions of JNK, c-Jun, P-c-Jun and HO-1 mRNA and its protein in the TXLSP+SP600125 group were significantly increased at different time points (P<0.05, P<0.01).</p><p><b>CONCLUSIONS</b>The vascular endothelial dysfunction under overfatigue conditions is related to the activity of the JNK/c-Jun/HO-1 pathway. One of the mechanisms of TXLSP in improving the vascular endothelial function is to adjust the activity of the JNK/c-Jun/HO-1 pathway at gene and protein levels.</p>
Assuntos
Animais , Humanos , Masculino , Ratos , Proteínas Sanguíneas , Farmacologia , Células Cultivadas , Citoproteção , Genética , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas , Farmacologia , Células Endoteliais , Metabolismo , Fadiga , Sangue , Metabolismo , Heme Oxigenase (Desciclizante) , Genética , Metabolismo , Fisiologia , Proteínas Quinases JNK Ativadas por Mitógeno , Genética , Metabolismo , Fisiologia , Tamanho da Partícula , Pós , Farmacologia , Proteínas Proto-Oncogênicas c-jun , Genética , Metabolismo , Fisiologia , Ratos Wistar , Soro , Metabolismo , Fisiologia , Transdução de Sinais , Genética , Fisiologia , Veias Umbilicais , Biologia Celular , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To observe the effects of Tongxinluo Supermicro Powder on the nuclear factor-kappaB (NF-kappaB), inter-cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression in aorta of rabbits fed with high-lipid diet.</p><p><b>METHODS</b>Healthy male New Zealand rabbits were randomly divided into 4 groups (n = 8 each): control group, model group, atorvastatin group (3 mg x kg(-1) x d(-1) per gavage), and Tongxinluo group (0.31 g x kg(-1) x d(-1) per gavage). At the end of 6 weeks, the expression of NF-kappaB, ICAM-1 and VCAM-1 were observed by immunochemistry methods, Western blotting and reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULT</b>The nuclear translocation of NF-kappaB in aortic endothelial cells and the gene expressions of NF-kappaB, ICAM-1 and VCAM-1 at protein and mRNA levels of the model group was significantly increased compared that in the control group (all P < 0.05), these effects could be significantly attenuated by atorvastatin and Tongxinluo Supermicro Powder (P < 0.01 vs. model group).</p><p><b>CONCLUSIONS</b>Similar as atorvastatin, Tongxinluo Supermicro Powder could relieve the process of atherosclerosis by decreasing the nuclear translocation of NF-kappaB and reducing the expression of ICAM-1, VCAM-1 in this model.</p>