氟伐他汀对阿霉素肾病大鼠肾脏清道夫受体A基因表达的影响及肾保护作用

目的：探讨氟伐他汀对阿霉素肾病（AN）大鼠肾脏清道夫受体A（SR-A）基因表达水平的影响及其肾保护作用。方法：将Wistar大鼠随机分为正常对照组、AN组和氟伐他汀治疗组。以尾静脉注射阿霉素制备AN大鼠模型，邻苯三酚自氧化法测定肾组织匀浆超氧化物岐化酶（SOD）活力，硫代巴比妥酸（TBA）法测定肾组织匀浆液丙二醛（MDA）水平，PCR和RT-PCR法检测大鼠肾脏SR-A基因表达水平。结果：AN组尿蛋白排泄量明显高于对照组和氟伐他汀组，电镜下肾小球上皮细胞足突融合，内皮细胞增生，严重者肾小球基膜增厚，模糊不清，内皮细胞呈连拱状。AN组大鼠血清TP和Alb低于正常对照组，而TG、TC、HDL、LDL、ApoA和ApoB则高于正常对照组，其肾组织匀浆MDA值升高，SOD值下降，肾脏SR-A基因表达水平升高；氟伐他汀治疗后血清TP和Alb水平升高，TG、TC、HDL、LDL、ApoA、ApoB水平和MDA值接近正常组（与AN组比较P〈0．05），肾脏SR-A基因表达水平有所下降，电镜下大部分肾小球上皮细胞足突较好，仅见少部分上皮细胞足突融合。结论：AN大鼠肾脏SR-A过度表达与肾脏脂质代谢异常有关，也是造成肾脏病理改变的主要原因之一；氟伐他汀通过抑制脂质过氧化和在转录水平阻抑SR-A的mRNA表达，从而起到非降脂肾保护作用。

Effects of Fluvastatin on Nephritic Gene Expression of Scavenger Receptor A and Renoprotective in Adriamycin Nephrosis Rat

Objoetive：To detective the effects of Fluvastatin on nephritic gene expression of scavenger receptor A （SR- A） and renoprotective in adriamycin nephrosis （AN） rat. Methods： Injecting adriamycin in veins of the rat＇s tail once was used to make AN model, thio- barbituric acid （TBA） metod was used to measure the levels of malonaldehyde （MDA）, pyrogallic acid autooxidation method was used to examing the levels of SOD, PCR and RT- PCR was used to measure the gene expression value of SR- A in different group of rat. Results.the urine protein of AN group was much more than contrast group and treatment with fluvastatin group （P〈0.05）, glomerulus epitheliumfoot process confluence, endodermis cell being ultro- growing, some much serious , the basis membrane of glomerulus being unclear, endodermis cell being archoid was seen with the electron microscope in AN rat. The levels of serum total protein , albumin and SOD in AN group were much lower than in contrast group and group of treatmenting with fluvastatin, while the levels of TG, TC, HDL, LDL, ApoA, ApoB and MDA were higher . The gene expression value of SRA was higher （0.74± 0.14）in AN group than in contrast group（ 1.17 ± 0.13） and group of treatmenting with fluvastatin （0.83 ± 0.14）. The pathologic changes were attenuated after treatmenting with fluvastatin. Conclusion： High expression of SRA maybe closed related to abnormal of lipid metabolism in AN rat, It may also be one of the main reasons of the kidney pathologic changes. Fluvastatin may have the function of renoprotective by anti - lipide peroxide and inhibiting the gene expression of SR - A in glomerulus mesangial cell.WORDS