酪氨酸羟化酶反义基因疗法对自发性高血压大鼠具有降压作用。
Tyrosine hydroxylase antisense gene therapy causes hypotensive effects in the spontaneously hypertensive rats.
作者信息
Kumai T, Tateishi T, Tanaka M, Watanabe M, Shimizu H, Kobayashi S
机构信息
Department of Pharmacology, St Marianna University School of Medicine, Kawasaki-shi, Japan.
出版信息
J Hypertens. 2001 Oct;19(10):1769-73. doi: 10.1097/00004872-200110000-00010.
We investigated the effect of antisense oligodeoxynucleotides (AS ODN) against tyrosine hydroxylase (TH) on hypertension and sympathetic nervous system activity in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP) in SHR treated with TH AS ODN (50, 200 microg/rat, i.v.) was significantly lower than that of control SHR. Epinephrine and norepinephrine levels, TH activity, and TH protein levels in the adrenal medulla of SHR were reduced concomitant with TH AS ODN treatment-induced changes in SBP. In contrast, TH AS ODN (200 microg/rat) had no effect on SBP in Wistar-Kyoto rats (WKY), despite significantly decreased catecholamine levels, TH activity, and TH protein levels. These findings suggest that peripheral systemic injection of TH AS ODN may be effective as hypotensive therapy in SHR.
我们研究了针对酪氨酸羟化酶（TH）的反义寡脱氧核苷酸（AS ODN）对自发性高血压大鼠（SHR）高血压及交感神经系统活性的影响。用TH AS ODN（50、200微克/大鼠，静脉注射）处理的SHR的收缩压（SBP）显著低于对照SHR。伴随TH AS ODN处理诱导的SBP变化，SHR肾上腺髓质中的肾上腺素和去甲肾上腺素水平、TH活性及TH蛋白水平降低。相比之下，尽管TH AS ODN（200微克/大鼠）使Wistar-Kyoto大鼠（WKY）的儿茶酚胺水平、TH活性及TH蛋白水平显著降低，但对其SBP没有影响。这些发现表明，外周全身注射TH AS ODN可能作为SHR的降压疗法有效。
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