Effects of metformin on inflammation and oxidative levels in hypothalamic paraventricular nucleus of salt-sensitive hypertensive rats / 中国基层医药

ABSTRACT

Objective To explore central mechanism of metformin(MET)in salt -sensitive hypertensive rats by assessing the effect of metformin on inflammation and oxidative stress in hypothalamic paraventricular nucleus (PVN),sympathetic nerve activity and blood pressure.Methods Eight -week -old male Dahl salt -sensitive rats were divided into 4 groupsthe normal -salt diet control group[0.3% NaCl +intracerebroventricular(ICV)artificial cerebrospinal fluid(aCSF)],the normal -salt diet with MET group(0.3% NaCl +ICV MET 25μg/d],the high -salt diet control group (8% NaCl +ICV aCSF),the high -salt diet with MET group (8% NaCl +ICV MET 25μg/d). Mean arterial pressure(MAP)was determined every week by a tail -cuff occlusion.After 6 weeks,all rats were eutha-nized,and blood and brain tissues were collected.Then,the plasma norepinephrine(NE,an indicator of sympathetic activity)was detected by enzyme linked immune sorbent assay(ELISA).The expression levels of interleukin(IL)-1β,IL -10 and NOX -2[a subunit of NAD(P)H oxidase],superoxide dismutase(SOD)in the PVN were detected by immunofluorescence,immunohistochemistry and Western blot methods.Reactive oxygen species(ROS)was detec-ted by dihydroethidium(DHE)staining.Results The MAP level of high -salt diet with metformin group was attenu-ated compared with that of the high -salt diet control group[(129.55 ±6.52)mmHg vs.(154.47 ±6.57)mmHg, F =121.90,P <0.05].The change of plasma NE level of high -salt diet with metformin group was lower compared with that of the high -salt diet control group[(364.57 ±30.73)pg/mL vs.(547.68 ±25.08)pg/mL,F =179.24, P <0.05].The expression levels of IL -1β,IL -6,NOX -2 and ROS were markedly higher in high -salt diet with metformin than those of the high -salt diet control group(F =27.80,21.20,22.48,31.99,all P <0.05),which of IL -10 and SOD was lower(F =17.69,23.69,all P <0.05).Conclusion Metformin may attenuate blood pressure in salt -sensitive hypertensive rats,at least partly via decreasing inflammatory molecules and inhibiting oxidative stress in the PVN,subsequently inhibiting sympathoexcitation.