Mechanism of Minocycline in Reducing Hypertension Induced by Two Kidneys and One Clip by Affecting the Activation Level of Microglia in the Paraventricular Nucleus of Hypothalamus
Objective:To observe the effects of minocycline on plasma inflammatory factor,neurotransmitter concentration and blood pressure in 2 kidney and 1 clip(2k1c) hypertensive rats,and to explore a regulatory role by hypothalamic paraventricular nucleus(PVN). Methods:Twenty-eight male specific pathogen free(SPF) grade SD rats were randomly divided into SHAM+artificial cerebrospinal fluid(aCSF) group,SHAM+minocycline group,2k1c+aCSF group,and 2k1c+minocycline group.The model was established by renal artery narrowing and paraventricular nuclear cannulation was performed,and the blood pressure of rats was monitored using a non-invasive blood pressure meter.Renal sympathetic nerve discharge(RSNA) detection was performed after 10 weeks.The number of activated microglia and the length of the cell process were measured by microglia staining. The contents of interleukin-1β( IL-1β),interleukin-6(IL-6),noradrenaline(NE),glutamic acid(GLU) and gamma-aminobutyric acid(GABA) in PVN were detected by high performance liquid chromatography(HPLC).Real-time quantitative polymerase chain reaction(PCR) was used to detect gp91phox mRNA expression in PVN.Plasma levels of IL-1β,IL-6,and NE were detected by enzyme-linked immunosorbent assay(ELISA).Results:Central chronic infusion of minocycline could reduce the number of activated microglia and increase the length of cell processes(P<0.05). The levels of IL-1β,IL-6 and NE in plasma and the GLU in PVN of the 2k1c+aCSF group and 2k1c+minocycline group were higher than those of the SHAM+aCSF group and SHAM+minocycline group(P<0.05),and minocycline could reverse the above expression (P<0.05).The GABA content of PVN in the 2k1c+aCSF group and 2k1c+minocycline group was lower than that in the SHAM+aCSF group and SHAM+minocycline group(P<0.05).GABA expression in the 2k1c+minocycline group effectively increased by minocycline treatment(P<0.05).Compared with SHAM+aCSF group and SHAM+minocycline group,gp91phox mRNA expression in PVN of 2k1c+aCSF group and 2k1c+minocycline group was increased(P<0.05).Minocycline decreased gp91phox mRNA expression in PVN(P<0.05).The renal sympathetic discharge in the 2k1c+aCSF group and 2k1c+minocycline group was higher than that in the SHAM+aCSF group and SHAM+minocycline group(P<0.05),and the renal sympathetic discharge was effectively weakened after minocycline treatment(P<0.05).Conclusion:Chronic infusion of minocycline could reduce hypertension by affecting the activation level of microglia in the paraventricular nucleus of hypothalamus.
hypertensionminocyclinetwo kidneys and one clipparaventricular nucleus of hypothalamusneurotransmitterratsexperimental study
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维普
