| Objective To explore the role of NOX2 in the inflammation of hypertension, we research on the correlation of the effect of Angiotensin II (Ang II) on NADPH oxidase2 (NOX2) and interleukin-1β(IL-1β) expression in peripheral blood mononuclear cells of spontaneously hypertensive rats (SHR) . To explore molecular mechanism of anti- hypertensive inflammatory of simvastatin, we further study the effect of simvastatin on Ang II-stimulated NOX2 and IL-1βexpression in peripheral blood mononuclear cells of SHR.Methods Peripheral blood mononuclear cells of male SHR were separated and cultured, and were randomly divided into several groups: blank control group, Ang II(10-8mol/L)group, Ang II(10-7mol/L)group, Ang II (10-6 mol/L)group, AngII (10-6mol/L) + diphenyleneiodonium (DPI, 10-5mol/L) group, Ang II (10-6 mol/L) + Simvastatin(1×10-6mol/L) group, Ang II (10-6mol/L)+ Simvastatin (5×10-6 mol/L) group, Ang II (10-6mol/L)+ Simvastatin (10×10-6 mol/L) group, Ang II (10-6 mol/L)+DMSO group. NOX2 and IL-1βmRNA expression in mononuclear cells was measured by RT-PCR, NOX2 protein expression was measured by Western blotting, and IL-1βprotein secretion was measured by ELISA. The experiment was divided into the following four parts: (1)In the first part, we studied the effect of different concentrations of Ang II on NOX2 expression in peripheral blood mononuclear cells of SHR. (2) In the second part, we studied the effect of DPI on AngII-stimulated NOX2 and IL-1β expression in peripheral blood mononuclear cells of SHR. (3) In the third part, we studied the effect of different doses of Simvastatin on AngII- stimulated IL-1βexpression in peripheral blood mononuclear cells of SHR. (4) In the fourth part, we studied the effect of Simvastatin on AngII-stimulated NOX2 expression in peripheral blood mononuclear cells of SHR.Results (1)Compared with that in blank control group, NOX2 mRNA expression in Ang II (10-8,10-7mol/L) groups were not significantly changed (P>0.05), which was significantly increased (P <0.01) in Ang II (10-6mol/L) groups. NOX2 protein expression in Ang II groups (10-8, 10-7, 10-6 mol/L) were all increased (P <0.01), more remarkably with higher concentration of Ang II. (2) Compared with that in blank control group, IL-1βmRNA expression and protein secretion in Ang II (10-6mol/L) group were significantly higher (mRNA: P<0.05, protein:P<0.01); Compared with that in Ang II(10-6mol/L) group, IL-1βmRNA expression in AngII (10-6mol/L) + DPI (10-5mol/L) group was not significantly changed (P>0.05), while IL-1βprotein secretion was significantly decreased (P <0.01). (3) Compared with that in Ang II(10-6 mol/L) group, Ang II-stimulated IL-1βmRNA expression and protein secretion were inhibited dose-dependently in Simvastatin groups (1×10-6mol/L, 5×10-6 mol/L, 10×10-6 mol/L), and the differences were all statistically significant (P< 0.01). (4) Compared with that in Ang II(10-6mol/L) group, NOX2 mRNA and protein expression in Ang II (10-6mol/L)+Simvastatin(10×10-6mol/L) group were both significantly decreased (P <0.01) .Conclusions (1) Ang II may promote NOX2 expression in peripheral blood mononuclear cells of hypertensin .(2) Ang II may promote NOX2 expression to increase inflammatory cytokines IL-1βsecretion in peripheral blood mononuclear cells of hypertension in post-transcriptional level. (3) Simvastatin may inhibit Ang II-stimulated IL-1βexpression in peripheral blood mononuclear cells of hypertension in a dose-dependent manner. (4) Simvastatin inhibiting Ang II-stimulated inflammatory cytokines IL-1βsecretion in peripheral blood mononuclear cells of hypertension is not only related with simvastatin inhibiting IL-1βgene expression, but also related with simvastatin inhibiting the activation of NOX2 in mononuclear cells.
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