缬沙坦与氟伐他汀单用及联用对阿霉素肾病大鼠血清肝细胞生长因子的影响

摘要/Abstract

摘要： 目的: 探讨缬沙坦与氟伐他汀单用及联用对阿霉素肾病大鼠肝细胞生长因子(hepatocy tegrow th facto r, HGF) 的影响。方法: 雄性SD 大鼠120 只, 适应性喂养2 周后, 随机抽取18 只为正常对照组(A 组);另外102 只制作阿霉素肾病模型。84 只造模成功大鼠随机分为4 组:B 组为模型对照组(等容积生理盐水,n =21), C 组为缬沙坦治疗组(缬沙坦35 mg ·kg^-1,d^-1, n =21),D 组为氟伐他汀治疗组(氟伐他汀10 mg,kg^-1,d^-1, n =21), E 组为缬沙坦与氟伐他汀联合治疗组(缬沙坦35 mg,kg^-1,d^-1加氟伐他汀10 mg, kg^-1,d^-1, n =21)。分别于2、6、10 周末, 遵循随机化原则, 按n =6 分层抽取各组样本, 收集24 h 尿液、血液及肾组织标本待测。结果: 和A 组相比, B 组、C 组、D 组和E 组24h 尿蛋白排泄、血清TC、TG 及HGF 浓度明显升高(P<0.01);缬沙坦与氟伐他汀单用及联用能减少尿蛋白排泄, 降低血清TC、TG 浓度(P<0.05 或P<0.01), 升高血清及肾脏HGF 浓度(P<0.05 或P<0.01)。结论: 缬沙坦与氟伐他汀可减轻阿霉素肾病大鼠蛋白尿, 降低血清TG、TC 浓度, 升高HGF 浓度, 联用时疗效更明显。提示缬沙坦与氟伐他汀至少部分通过升高HGF浓度而减轻肾脏损害。

关键词: 阿霉素肾病, 缬沙坦, 氟伐他汀, 肝细胞生长因子

Abstract: AIM: To investigate the influence of valsartan alone and in combination with fluvastatin on hepatocy tegrow th factor (HGF) in adriamycin (ADR)-induced nephroticrat models. METHODS: Male Sprague-Daw ley(SD) rats were randomly separated intofiveg roups and given dif ferent the rapies.18 no rmal rats wer as no rmal cont rolg roup (group A, n =18).Nephrot icmodel was induced by tail int roveno usly inject ion of ADR (6.0 mg/kg).Eighty-four ADR-induced nephrotic male SD rats were randomly separated into 4 groups:without treatment group (group B:normal saline, n =21), valsartant reatment group(group C, valsartan 35 mg, kg^-1,d^-1, n=21), fluvastatint reatment group(group D, fluvastatin 10 mg ·kg^-1,d^-1, n=21) and combined treatment group(group E, valsartan 35 mg ·kg^-1 ·d^-1 plusfluv astatin 10 mg, kg^-1,d^-1, n=21).After the end of the therapies for 2, 6, and 10 weeks, the samples of 24 h urine, serum were collected and assayed (sixrat swere assigned randomly in every group). RESULTS: Compared with group A, 24 h urinary protein excretion, the serum levels of total cholesterol, trigly ceride and HGF were increased significantly in group B, C, D, E (P< 0.01).Treatment with either valsartan or fluvastatin or combined with valsar tan and fluvastatin could reduce 24 h urinary protein excretion, reduce the serum levels of to tal cho lesterol, trigly ceride (P<0.05 or P<0.01), increase the levels of HGF in serium and renal. CONCLUSION: Valsartan and fluvastat in can decrease proteinuria, decrease serum triglyce ride, total cho leste rol and increase the HGF in ADR-induced nephrotic rats.Combination of valsa rtan and f luv astatin has superiority overmo no therapies on renal protection. These results suggest that valsar tan and fluvastatin may mediated through, at least partly, increasing serum and renal HGF level and at tenuating renal damage.

Key words: Adriamy cin-induced nephropathy, Valsartan, Fluv astatin, Hepatocy tegrowh

中图分类号:

R965.2

吴小冬, 张道友, 崔明春, 杨利才, 杨沿浪, 朱新俭. 缬沙坦与氟伐他汀单用及联用对阿霉素肾病大鼠血清肝细胞生长因子的影响[J]. 中国临床药理学与治疗学, 2010, 15(3): 305-309.

WU Xiao-dong, ZHANG Dao-you, CUI Ming-chun, YANG Li-cai, YANG Yan-lang, ZHU Xin-jian. Influence of valsartan and fluvastatin on hepatocyte growth factor in adriamycin-induced nephrotic rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(3): 305-309.

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