高胆固醇血症对健康大鼠肾脏形态学的影响
作者：何永成 廖履坦 丁小强 张月娥 徐元钊 徐元鼎
单位：何永成(上海医科大学附属中山医院肾内科 上海，200032)；廖履坦(上海医科大学附属中山医院肾内科 上海，200032)；丁小强(上海医科大学附属中山医院肾内科 上海，200032)；张月娥(上海医科大学基础医学院病理教研室)；徐元钊(上海医科大学附属中山医院肾内科 上海，200032)；徐元鼎(上海医科大学基础医学院形态研究中心)
关键词：高胆固醇血症；肾小球损害；脂质肾毒性
肾脏病与透析肾移植杂志000109 摘 要 目的：探讨高胆固醇血症对健康大鼠肾脏形态学的影响。 方法：用5%高胆固醇饲料喂养健康雄性Wistar大鼠，分别于实验第30、60和90天进行肾脏的形态学观察。 结果：自实验第30天起，高胆固醇组表现为进行性肾小球系膜细胞增生，系膜基质增多，炎性细胞浸润，肾小球毛细血管塌陷，肾小球上皮细胞足突灶性融合，肾小管上皮细胞水样变性，肾小球体积进行性增大。电镜未发现肾小球内电子致密物沉积，直接免疫荧光显示肾组织IgG阴性。相关分析显示，血浆总胆固醇(TCh)及低密度脂蛋白(LDL)浓度与肾小球细胞数、肾小球PAS阳性物质积分光密度值及肾小球体积呈显著正相关。 结论：饮食诱导的高胆固醇血症可导致健康大鼠肾脏非免疫复合物介导的病理损害，病变的程度与血浆TCh及LDL浓度呈正相关。
, 百拇医药
EFFECT OF DIET-INDUCED HYPERCHOLESTEROLEMIA ON RENAL MORPHOLOGY IN HEALTHY RATS
HE Yongcheng LIAO lütan DING Xiaoqiang ZHANG Yuee XU Yuanzhao XU Yuanding
(Department of Nephrology，Zhongshan Hospital，Shanghai Medical University，Shanghai 200032)
OBJECTIVE To study the effect of hypercholesterolemia on renal morphology in healthy rats.
METHODOLOGY Male wistar rats were fed with normal rodent chow(control group)or supplemented with 5% cholesterol(group E).Renal pathology and image analysis were made by light microscope，immunofluorescence，electronic microscope at day 30，60，and 90. RESULTS Significant elevations of plasma total cholesterol(TCh)(2.38±0.84 vs 1.67±0.12 mmol/L，P<0.05)and low density lipoprotein(LDL)(1.43±0.41 vs 0.35±0.10 mmol/L，P<0.05)were found in group E at day 30.Progressive increments in TCh and LDL were observed during the experiment.Mesangial hypercellularity，increased mesangial matrix，inflammatory cell infiltration and collapsed glomerular lesions were observed in progressive severity in group E.Electronic microscopic findings showed large amount of lipid appeared in endothelial and mesangial cells，increased number of meangial cells and expanded mesangial matrix and focal fusion of epithelial foot processes in group E.No electronic dense deposit was found in any of the glomeruli examined.Direct immunofluorescence was negative for IgG in kidneys from all groups.Image analysis indicated glomerular enlargement in group E.There was a significant positive correlation between glomerular size and plasma TCh，or LDL levels，number of glomerular cells，or integral light density(ILD)of PAS positive substance in glomeruli. CONCLUSION The diet-induced hypercholesterolemia may cause renal pathological injury in rats，the severity of renal injury is closely correlated with plasma TCh and LDL.
, 百拇医药
Key words hypercholesterolemia glomerular lesion lipid nephrotoxicity
Moorhead等[1]于1982年首次提出了“脂质肾毒性”(lipid nephrotoxicity)假说，认为脂质代谢异常可导致肾小球的损害及肾脏疾病的进行性发展。其后，一些动物实验已证明了高脂血症与肾损害之间存在密切关系，如发现高脂饮食可使氨基核苷和阿霉素诱导的局灶性肾小球硬化加重，而通过药物降低血浆中脂质浓度可有效防止肾小球硬化[2]；给正常大鼠及豚鼠喂养高胆固醇饲料，发现高胆固醇血症可导致正常大鼠和豚鼠肾脏病变[2～4]。本研究在建立高胆固醇血症动物模型基础上，通过对实验动物连续的生化及肾脏病理形态学观察，以探讨高胆固醇血症对健康Wistar大鼠肾脏形态学的影响。
1 材料和方法
, 百拇医药
1.1 材料 雄性Wistar大鼠，225～250 g，平均14周龄
单位：何永成(上海医科大学附属中山医院肾内科 上海，200032)；廖履坦(上海医科大学附属中山医院肾内科 上海，200032)；丁小强(上海医科大学附属中山医院肾内科 上海，200032)；张月娥(上海医科大学基础医学院病理教研室)；徐元钊(上海医科大学附属中山医院肾内科 上海，200032)；徐元鼎(上海医科大学基础医学院形态研究中心)
关键词：高胆固醇血症；肾小球损害；脂质肾毒性
肾脏病与透析肾移植杂志000109 摘 要 目的：探讨高胆固醇血症对健康大鼠肾脏形态学的影响。 方法：用5%高胆固醇饲料喂养健康雄性Wistar大鼠，分别于实验第30、60和90天进行肾脏的形态学观察。 结果：自实验第30天起，高胆固醇组表现为进行性肾小球系膜细胞增生，系膜基质增多，炎性细胞浸润，肾小球毛细血管塌陷，肾小球上皮细胞足突灶性融合，肾小管上皮细胞水样变性，肾小球体积进行性增大。电镜未发现肾小球内电子致密物沉积，直接免疫荧光显示肾组织IgG阴性。相关分析显示，血浆总胆固醇(TCh)及低密度脂蛋白(LDL)浓度与肾小球细胞数、肾小球PAS阳性物质积分光密度值及肾小球体积呈显著正相关。 结论：饮食诱导的高胆固醇血症可导致健康大鼠肾脏非免疫复合物介导的病理损害，病变的程度与血浆TCh及LDL浓度呈正相关。
, 百拇医药
EFFECT OF DIET-INDUCED HYPERCHOLESTEROLEMIA ON RENAL MORPHOLOGY IN HEALTHY RATS
HE Yongcheng LIAO lütan DING Xiaoqiang ZHANG Yuee XU Yuanzhao XU Yuanding
(Department of Nephrology，Zhongshan Hospital，Shanghai Medical University，Shanghai 200032)
OBJECTIVE To study the effect of hypercholesterolemia on renal morphology in healthy rats.
METHODOLOGY Male wistar rats were fed with normal rodent chow(control group)or supplemented with 5% cholesterol(group E).Renal pathology and image analysis were made by light microscope，immunofluorescence，electronic microscope at day 30，60，and 90. RESULTS Significant elevations of plasma total cholesterol(TCh)(2.38±0.84 vs 1.67±0.12 mmol/L，P<0.05)and low density lipoprotein(LDL)(1.43±0.41 vs 0.35±0.10 mmol/L，P<0.05)were found in group E at day 30.Progressive increments in TCh and LDL were observed during the experiment.Mesangial hypercellularity，increased mesangial matrix，inflammatory cell infiltration and collapsed glomerular lesions were observed in progressive severity in group E.Electronic microscopic findings showed large amount of lipid appeared in endothelial and mesangial cells，increased number of meangial cells and expanded mesangial matrix and focal fusion of epithelial foot processes in group E.No electronic dense deposit was found in any of the glomeruli examined.Direct immunofluorescence was negative for IgG in kidneys from all groups.Image analysis indicated glomerular enlargement in group E.There was a significant positive correlation between glomerular size and plasma TCh，or LDL levels，number of glomerular cells，or integral light density(ILD)of PAS positive substance in glomeruli. CONCLUSION The diet-induced hypercholesterolemia may cause renal pathological injury in rats，the severity of renal injury is closely correlated with plasma TCh and LDL.
, 百拇医药
Key words hypercholesterolemia glomerular lesion lipid nephrotoxicity
Moorhead等[1]于1982年首次提出了“脂质肾毒性”(lipid nephrotoxicity)假说，认为脂质代谢异常可导致肾小球的损害及肾脏疾病的进行性发展。其后，一些动物实验已证明了高脂血症与肾损害之间存在密切关系，如发现高脂饮食可使氨基核苷和阿霉素诱导的局灶性肾小球硬化加重，而通过药物降低血浆中脂质浓度可有效防止肾小球硬化[2]；给正常大鼠及豚鼠喂养高胆固醇饲料，发现高胆固醇血症可导致正常大鼠和豚鼠肾脏病变[2～4]。本研究在建立高胆固醇血症动物模型基础上，通过对实验动物连续的生化及肾脏病理形态学观察，以探讨高胆固醇血症对健康Wistar大鼠肾脏形态学的影响。
1 材料和方法
, 百拇医药
1.1 材料 雄性Wistar大鼠，225～250 g，平均14周龄