下丘脑室旁核CBS 通过影响PGC-1α 降低自发性高血压大鼠的血压

Objective To elueidate how the overexpression of cystathionine-ß-synthase (CBS) plays an antihypertensive role by affecting peroxisome proliferator-activated reeeptor y coactivator-la (PGC-la) expression. Methods The adeno-associated viruses (AAVs), ones that overexpressed CBS, and another knocked down PGC-la, were injeeted into the hypothalamic paraventricular nucleus (PVN) of spontaneously hypertensive rats (SHRs). The rats' blood pressure was monitored, and the level of norepinephrine (NE) was examined by ELISA; PVN inflammatory response, oxidative stress and tyrosine hydroxylase (TH) expression were detected with RT-qPCR and immunofluorescence. Results PVN overexpression of CBS could increase the transcription level of CBS (by 3.8 times, P<0.05) and PGC-la (by 1.6 times, P<0.05) in PVN of SHR. PVN overexpression of CBS could reduce blood pressure in SHR (from 177.81 mmHg to 128.77 mmHg, P<0.001), but PVN knockdown of PGC-la weakened such effect (from 128.77 mmHg to 152.79 mmHg, P<0.05). PVN overexpression of CBS could alleviate PVN inflammatory response and oxidative stress, but this effect was weakened or even eliminated when knocking down PGC-la was performed at the same time. Conclusion PVN overexpression of CBS can reduce blood pressure in SHR, and this effect may be achieved by increasing the transcriptional level of PGC-la, alleviating PVN inflammatory response, oxidative stress, and improving sympathetic nerve excitation.