RESUMO
To investigate the protective effects of recombinant human tumor necrosis factor receptor II: IgG Fc fusion protein (rhu TNFR: Fc) against the lipopolysaccharide (LPS) induced intestinal damage of rats and its underlying mechanism. SD rats were randomly divided into four groups: control group, rhuTNFR: Fc group, LPS group and rhu TNFR: Fc + LPS group. Mean arterial pressure (MAP) was continuously monitored and the mortality rates were assessed. The levels of TNF-alpha and its bioactivity in the serum were assessed by ELISA and flow cytometry respectively. Pathologic changes of intestinal tissue were observed by HE staining. The rats of control and rhu TNFR: Fc group all survived with stable MAP, and the low level and bioactivity of TNF-alpha in the serum were maintained. While 83% of the rats in LPS group died by 6 h with the levels and bioactivity of TNF-alpha increasing significantly. In rhu TNFR: Fc + LPS group, the mortality rate of rats dropped to 33%. The TNF-alpha level increased compared with control group but its bioactivity decreased significantly compared with LPS group. The MPO activity and content of MDA decreased significantly. The status of pathological manifestation in the intestine was also ameliorated. These data suggest that rhu TNFR: Fc could protect rats from the acute intestine injury induced by LPS through ablating the rise in serum TNF-alpha level and bioactivity as well as anti-oxidation.
Assuntos
Animais , Feminino , Humanos , Masculino , Ratos , Modelos Animais de Doenças , Etanercepte , Imunoglobulina G , Farmacologia , Intestinos , Metabolismo , Patologia , Lipopolissacarídeos , Ratos Sprague-Dawley , Receptores do Fator de Necrose Tumoral , Receptores Tipo II do Fator de Necrose Tumoral , Farmacologia , Proteínas Recombinantes de Fusão , Farmacologia , Fator de Necrose Tumoral alfa , MetabolismoRESUMO
<p><b>OBJECTIVES</b>To block the synthesis of ryanodine receptor 2 (RyR2) in myocardial cells by RNA interference and to investigate its biological impact on ischemia-reperfusion (I/R) in rat myocardial cells.</p><p><b>METHODS</b>Rat myocardial cells were isolated and cultured for an I/R model in vitro. RNA interference technique was used to block the synthesis of RyR2 in myocardial cells. Changes of LDH level, apoptosis, RyR2 mRNA expression and cytosolic Ca(2+) concentration were analyzed accordingly.</p><p><b>RESULTS</b>Myocardial cells after I/R manipolation were severely injuried (LDH leakage, 125 IU/L vs 12 IU/L, P < 0.05), apoptosis (60.1% vs 5.5%, P < 0.05), significant cytosolic Ca(2+) overload (21.2 vs 7.6, P < 0.05) and remarkable mitochondrial membrane potential loss (37.2 vs 85.1, P < 0.05). However, no visible change of RyR2 was observed (20.1 vs 22.7, P > 0.05). Pre-treatment with RyR2 specified siRNA demonstrated suppressed expression of RyR2 (6.8 vs 20.1, P < 0.05), increased mitochondrial membrane potential (55.8 vs 37.2, P < 0.05), attenuated cytosolic Ca(2+) overload (8.6 vs 21.2) and cellular apoptosis (31.2% vs 60.1%, P < 0.05).</p><p><b>CONCLUSION</b>RyR2 gene silencing enables to protect myocardial cells from I/R injury in vitro.</p>
Assuntos
Animais , Ratos , Apoptose , Genética , Células Cultivadas , Inativação Gênica , Alergia e Imunologia , Fisiologia , Potencial da Membrana Mitocondrial , Alergia e Imunologia , Traumatismo por Reperfusão Miocárdica , Alergia e Imunologia , Patologia , Miócitos Cardíacos , Patologia , Oxigênio , Metabolismo , Interferência de RNA , RNA Interferente Pequeno , Farmacologia , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Alergia e Imunologia , Patologia , Canal de Liberação de Cálcio do Receptor de Rianodina , GenéticaRESUMO
Objective To study the effect of myocardial ischemic preconditioning on activity of ATPase and creatine kinase(CK) in high blood fat rat. Methods High blood fat rat mode was established from SD rats.The rats were randomly divided into three groups: ischemic preconditioning(IPC), ischemic/reperfusion(I/R) and control group.The activity of CK in coronary outflow,the activity of malonyldialdehyde(MDA),superoxide dismutase(SOD),glutathione perodxidase(GSH-Px) and ATPase in myocardium were dectected. Results CK and MDA were significantly less in IPC group than those in I/R group.In IPC group,the activity of SOD,GSH-Px,Na~(+)-K~(+)-ATPase,Ca~(2+)-ATPase and Ca~(2+)-Mg~(2+)-ATPase were much higher than those in I/R group. Conclusion Myocardial ischemic preconditioning can protect high blood fat rat from ischemic/reperfusion injury.