Michihara Akihiro
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Gakuencho, Fukuyama 72-0292, Japan.
Yakugaku Zasshi. 2004 Oct;124(10):683-92. doi: 10.1248/yakushi.124.683.
The spontaneously hypertensive rat (stroke-prone) (SHRSP) experiences severe hypertension and cerebral hemorrhage. The serum cholesterol level in this rat is lower than that in the normotensive Wistar-Kyoto rat. Epidemiologic studies have indicated a negative association between serum cholesterol level and the incidence of cerebral hemorrhage in humans. Therefore the low level of serum cholesterol in SHRSP may cause cerebral strokes. The following investigation demonstrated that the activity for the biosynthesis of cholesterol is decreased in SHRSP due to the reduced activity of mevalonate pyrophosphate decarboxylase (MPD). However, the mechanism underlying the reduced activity of this enzyme remains unclear. In this review, we indicate that the level of MPD in the brain and liver of SHRSP is reduced from the age of 2 weeks.
自发性高血压大鼠(易中风型)(SHRSP)会出现严重高血压和脑出血。该大鼠的血清胆固醇水平低于正常血压的Wistar-Kyoto大鼠。流行病学研究表明,血清胆固醇水平与人类脑出血发病率之间呈负相关。因此,SHRSP中血清胆固醇水平低可能导致脑中风。以下研究表明,由于甲羟戊酸焦磷酸脱羧酶(MPD)活性降低,SHRSP中胆固醇生物合成活性降低。然而,该酶活性降低的潜在机制仍不清楚。在本综述中,我们指出,从2周龄起,SHRSP脑和肝脏中的MPD水平就降低了。