单独应用贝特类降脂药治疗高脂血症肾损害大鼠的机制探讨

Mechanism of fibrate alone for hyperlipidemia kidney damage in rats

目的探讨单独应用非诺贝特降脂药物降脂治疗及其保护高脂血症肾损害的机制。方法随机将30只雄性SD大鼠分为对照组、高脂组、治疗组,每组10只,实验共观察12周。测量3组大鼠的血脂、24 h尿蛋白排出量(UPE)、内生肌酐清除率(Ccr)、尿N-乙酰-B-D-氨基葡萄糖苷酶(NAG)及尿渗透压Uosm的变化,并同时监测血、尿和肾组织匀浆中一氧化氮(NO)和内皮素(ET)的改变。结果治疗组的血脂水平较高脂组显著降低(P<0.05),尿蛋白(LUS)及尿NAG的排出显著减少(P<0.01);血、尿及肾组织NO显著升高,而ET含量则显著降低(P<0.05)。结论单独应用非诺贝特降脂药物时能显著降低高脂血症肾损害,非诺贝特除了有降脂的作用外,还能使血清、尿及肾组织的NO水平升高,并且能同时使ET的水平降低。非诺贝特治疗高脂血症肾损害的重要机制之一可能是通过改变血、尿、肾组织中的NO和ET水平来保护肾脏组织。

Objective To investigate the renal damage protection mechanism of lipid-lowering drug fenofibrate alone. Methods A total of 30 male SD rats were randomly divided into a normal control group, a hyperlipidemia model group, and a fenofibrate treatment group, 10 rats in each group, and the rats were observed for 12 weeks. We mea- sured the lipid, 24 h urinary protein excretion （UPE）, endogenous creatinine clearance rate （Ccr）, urine N-acetyl-BD- gtucosaminidase （NAG） and urine osmolality Uosm in the 3 groups, and simultaneously monitored the blood, urine and kidney tissue homogenates of nitric oxide （NO） and endothelin （ET）. Results The lipid level in the fenofibrate treatment group was decreased significantly than that of the fat model group （P 〈 0.05）; A significant reduction in uri- nary protein （LUS） and urinary excretion ofNAG＇s （P 〈 0.01） was also found. The NO levels in the blood, urine and renal tissue were significantly higher, while the ET content was significantly lower （P 〈 0.05）. Conclusion Fenofi- brate can significantly reduce hyperlipidemia and kidney damage when lipid-lowering drug fenofibrate is used alone. Besides lipid-lowering function, fenofibrate, but also increases the NO levels in the serum, urine and renal tissues, and simultaneously reduces the ET. One important mechanism of fenofibrate for kidney damage by hyperlipidemia may be changing the levels of NO and ET in the blood, urine and renal tissue to protect the kidney tissue.