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洛伐他汀与依那普利联合用于进行性肾病模型

The combination of lovastatin and enalapril in a model of progressive renal disease.

作者信息

Brouhard B H, Takamori H, Satoh S, Inman S, Cressman M, Irwin K, Berkley V, Stowe N

机构信息

Department of Pediatrics, Cleveland Clinic Foundation, Ohio 44195.

出版信息

Pediatr Nephrol. 1994 Aug;8(4):436-40. doi: 10.1007/BF00856524.

Abstract

Puromycin-induced nephrotic syndrome is an animal model of progressive renal disease. Both angiotensin converting enzyme inhibitors and lipid-lowering agents have been used to preserve renal structure and function in this model, although neither completely prevents progression. We tested the hypothesis that the combination of the two agents would be more protective than either alone. Rats were divided into five groups; all were uninephrectomized. Four groups were given puromycin at a dose of 10 mg/100 g body weight (BW) with additional doses of 4 mg/100 g BW given intraperitoneally at 4, 5, and 6 weeks thereafter. One group was given enalapril (EN) 50 mg/l dissolved in the drinking water; the second received lovastatin (L) 15 mg/kg given daily by gavage; the third received both agents; the fourth was left untreated, and the final group received no puromycin and served as the control group. Eight weeks after the initial dose of puromycin, glomerular filtration rate (GFR), as inulin clearance, and protein excretion were determined and blood was collected for cholesterol and triglycerides. Blood pressure was not different between any of the groups. At the end of the study period, serum cholesterol [mean +/- SD, 252 +/- 185 mg/dl (L), 135 +/- 101 mg/dl (L + EN)] and triglycerides (239 +/- 200, 148 +/- 158 mg/dl) were significantly lower (P < 0.001) in the lovastatin-treated groups than in the untreated puromycin group (535 +/- 255 mg/dl and 579 +/- 561 mg/dl, cholesterol and triglyceride, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

嘌呤霉素诱导的肾病综合征是一种进行性肾脏疾病的动物模型。血管紧张素转换酶抑制剂和降脂药物都已被用于在该模型中保护肾脏结构和功能,尽管两者都不能完全阻止疾病进展。我们检验了两种药物联合使用比单独使用更具保护作用的假设。将大鼠分为五组;所有大鼠均进行了单侧肾切除。四组大鼠以10 mg/100 g体重(BW)的剂量给予嘌呤霉素,并在之后的第4、5和6周腹腔内额外给予4 mg/100 g BW的剂量。一组给予溶解于饮用水中的依那普利(EN)50 mg/l;第二组每天经口灌胃给予洛伐他汀(L)15 mg/kg;第三组给予两种药物;第四组不进行治疗,最后一组不给予嘌呤霉素并作为对照组。在首次给予嘌呤霉素8周后,测定肾小球滤过率(GFR,以菊粉清除率表示)和蛋白质排泄,并采集血液检测胆固醇和甘油三酯。各组之间血压无差异。在研究期结束时,洛伐他汀治疗组的血清胆固醇[平均值±标准差,252±185 mg/dl(L组),135±101 mg/dl(L + EN组)]和甘油三酯(239±200,148±158 mg/dl)显著低于未治疗的嘌呤霉素组(分别为535±255 mg/dl和579±561 mg/dl,胆固醇和甘油三酯)(摘要截断于250字)

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