动物造模 z-bio 2022-07-15 255

　　Objective: To investigate whether pro-inflammatory cytokines in the paraventricular nucleus of hypothalamus in spontaneously hypertensive rats promote the hyperactivity of sympathetic nerves, and whether N-methyl-D-aspartate receptors mediate the above effects.

　　Methods: Adult SHR and normotensive Wistar-Kyoto (WKY) rats were used in this study. The protein expressions of tumor necrosis factor (TNF) and interleukin (IL)-1β receptor IL-1RI in the paraventricular nucleus of the hypothalamus were determined by Western blot and enzyme-linked immunosorbent assay (ELISA), respectively. TNF-α and IL-1β levels. And the application of brain stereotaxic for PVN micro-injection. Determination of renal sympathetic nerve activity Powerlab system was used to record the renal sympathetic nerve trunk electrical activity, and integral processing was performed to compare the changes of RSNA before and after administration. The carotid artery cannula was connected to the PowerLab system via a pressure transducer to record and analyze mean arterial blood pressure.

　　Results: Compared with WKY rats, the levels of TNF-α and IL-1β in SHR PVN, as well as the protein expressions of TNF-α receptors p55TNFR, p75TNFR and IL-1β receptor IL-1RI were significantly increased (P<0.05). . Microinjection of Etanercept or IL-1ra into PVN to block the effects of TNF-α and IL-1β decreased sympathetic nerve activity more significantly in the SHR group (P < 0.05). Microinjection of NMDAR antagonists DL-2-amino-5-phosphonovaleric acid (APV) or MK-801 (Dizocilpine) into PVN reduced RSNA and MAP in both SHR and WKY groups (P<0.05), and this effect was observed in SHR group More significant (P < 0.05); in addition, APV or MK-801 pretreatment to block NMDA receptors in PVN significantly attenuated PVN microinjection of TNF-α or IL-1β to enhance RSNA and increase MAP in SHR and WKY groups. effect (P < 0.05), which was more significant in the SHR group (P < 0.05) compared with the WKY group.

　　Conclusion: The expressions of pro-inflammatory cytokines TNF-α, IL-1β and their receptors in SHR PVN are increased, and NMDA receptors in PVN mediate TNF-α and IL-1β in PVN of SHR rats to enhance sympathetic activity and increase blood pressure. high effect.