高脂血症大鼠肾脏Angptl4变化及辛伐他汀的保护作用

为探讨高脂血症大鼠（Rattus norregicus）肾脏中Angptl4的变化及辛伐他汀的保护作用，将45只雄性SD大鼠随机平均分为3组：正常对照组（NG）给予普通饲料喂养；高脂饮食组（HG）给予高脂饲料喂养；辛伐他汀组（SG）在高脂饲料喂养的基础上给予辛伐他汀10mg·kg^-1·d^-1水溶液灌胃。分别于第4、6、lO周时各组随机选取5只大鼠，检测大鼠24h尿蛋白及血清总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）水平，石蜡切片HE染色观察大鼠肾小球的损害，免疫组化及Western blot检测大鼠肾脏Angptl4蛋白分布及表达。结果显示，于第4周开始，HG组和sG组大鼠血清TC和LDL-C水平升高。实验第10周时，HG组和SG组大鼠24h尿蛋白定量升高；大鼠肾组织HE染色光镜下观察显示：肾小球呈轻微分叶状，系膜区增宽和基质增多不明显，但肾小球内有较明显的空泡变性，SG组大鼠的病变明显轻于HG组；免疫组化和免疫印迹检查发现，大鼠肾脏Angptl4明显增多，SG组的表达较HG组有减少。研究认为，高脂血症可引起肾脏肾小球明显病变，可能是肾小球内的足细胞分泌Angptl4的增多引起；而辛伐他汀则可能使高脂饮食时足细胞分泌Angptl4减少，从而减轻高脂血症时肾小球受到的损害。

The Changes of Angptl4 in the Kidney of Hyperlipidemic Rats and the Protective Effect of Simvastatin

To investigate the changes in the expression of Angptl4 in the kidney of hyperlipidemic rats （Rattus norregicus） and the protective effect of simvastatin, 45 individuals of SD rats were randomly divided into 3 groups. The control group （n= 15） was fed with normal diet. The high fat group （n=15） was fed with high fat diet. The simvastatin group （n=15） was fed with high fat diet plus with simvastatin solution garage （10 mg·kg^-1·d^-1 ）. 5 rats were sampled randomly from each group at week 4, 6, and 10, respectively. The urinary protein excretion during 24 h, the serum cholesterol concentration, and the low density lipoprotein concen- tration were determined. The changes in histopathology of glomeruli were detected by paraffin section and microscope and the distri- bution and expression of Angptl4 were determined by immunohistochemistry and Western blot. The results showed that： The serum cholesterol concentration and the low density lipoprotein concentration increased significantly in high fat group and simvastatin group at week 4. At week 10, The 24 h urinary protein concentrations of high fat group and simvastatin group were significantly higher than the control group ; The results of HE staining showed that the width of mesangial region and matrix did not significantly in- crease, there were obvious degenerations in the glomeruli especially in the high fat group, The glomeruli of high fat group showed light differential leaflike and weakly increase in the size of mesangial region and matrix, but obvious degeneration, suggesting heavier lesions in high fat group compared to simvastatin group. The results of immunohistochemical examination and Western blot showed that Angptl4 expressed more in the kidneys of high fat group than that of simvastain group. The research indicated that hyperlipi- demia can cause significant kidney glomerular lesions, which could be due to the increase of glomerular podocyte secretion. And sim- vastatin may make high fat diet podocyte secretion of Angptl4 reduced, to protect the hypercholesterolemia glomerular damage.