Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Nutrition. 2010 Nov-Dec;26(11-12):1176-80. doi: 10.1016/j.nut.2009.10.010. Epub 2010 Feb 4.
Increased oxidative stress plays an important role in cardiovascular diseases including hypertension and stroke. Evidence has indicated that ketone bodies could exert antioxidative effects. We explored the role of renal mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMGCS2) expression, a key control site of ketogenesis, in stroke-prone spontaneously hypertensive rats (SHRSPs) and their ancestral hypertensive but stroke-resistant spontaneously hypertensive rats (SHRs).
Two groups of SHRSPs were fed a standard chow or standard chow supplemented with clofibrate (an agonist of HMGCS2 promoter), respectively, and SHRs fed with a standard chow were used as controls. The renal levels of HMGCS2, Akt, and phosphorylated protein kinase B (Akt) were measured by western blotting. Malondialdehyde, catalase, superoxide dismutase, and glutathione peroxidase were detected by assay kits.
Compared with SHRs, lower HMGCS2 protein expression, enhanced phosphorylated Akt signal, higher malondialdehyde levels, and higher catalase activity were observed in kidney tissues in SHRSPs (P < 0.05). No differences in superoxide dismutase and glutathione peroxidase activities were observed between SHRSPs and SHRs. Clofibrate treatment significantly upregulated renal HMGCS2 expressions, inhibited phosphorylation of Akt, and decreased malondialdehyde levels and catalase activities in SHRSP kidney tissues (P < 0.05).
These results demonstrated the difference in HMGCS2 expression and oxidative stress in kidney tissues between SHRSPs and their SHR controls. The enhanced oxidative stress was partly due to the lower HMGCS2 expression regulated possibly by the Akt signaling pathway.
氧化应激增加在包括高血压和中风在内的心血管疾病中起重要作用。有证据表明酮体具有抗氧化作用。我们探讨了肾脏线粒体 3-羟-3-甲基戊二酰辅酶 A 合酶（HMGCS2）表达（酮体生成的关键控制部位）在易卒中型自发性高血压大鼠（SHRSP）及其祖高血压但中风抵抗自发性高血压大鼠（SHR）中的作用。
两组 SHRSP 分别喂食标准饲料或添加氯贝特（HMGCS2 启动子激动剂）的标准饲料，而喂食标准饲料的 SHR 作为对照。通过 Western 印迹法测定肾脏 HMGCS2、Akt 和磷酸化蛋白激酶 B（Akt）的水平。通过试剂盒测定丙二醛、过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶。
与 SHR 相比，SHRSP 肾脏组织中 HMGCS2 蛋白表达降低，磷酸化 Akt 信号增强，丙二醛水平升高，过氧化氢酶活性升高（P < 0.05）。SHRSP 和 SHR 之间超氧化物歧化酶和谷胱甘肽过氧化物酶活性无差异。氯贝特治疗显著上调 SHRSP 肾脏 HMGCS2 表达，抑制 Akt 磷酸化，降低肾脏丙二醛水平和过氧化氢酶活性（P < 0.05）。
这些结果表明 SHRSP 与其 SHR 对照之间肾脏组织中 HMGCS2 表达和氧化应激存在差异。增强的氧化应激部分归因于 Akt 信号通路调节的 HMGCS2 表达降低。
