苯那普利对糖尿病大鼠肾皮质血小板衍化生长因子-B及其β受体表达的影响

Effects of Benazepril on the expression of platelet derived growth factor PDGF B chain and its β receptor in diabetic rat renal cortex

目的 探讨血管紧张素转换酶抑制剂（ Ａ Ｃ Ｅ Ｉ） 苯那普利对单侧肾切除糖尿病大鼠肾皮质血小板衍化生长因子 Ｂ（ Ｐ Ｄ Ｇ Ｆ Ｂ） 及其β受体表达的影响。方法 苯那普利（１０ｍｇ·ｋｇ１·ｄ１ 灌胃） 治疗４ 周后应用荧光分光光度法检测各组血浆和肾皮、髓质 Ａ Ｃ Ｅ 活性；用免疫组织化学方法检测肾皮质Ⅳ型胶原、纤维连接蛋白（ Ｆ Ｎ） 及 Ｐ Ｄ Ｇ Ｆ Ｂ 蛋白表达；用 Ｎｏｒｔｈｅｒｎ 和 Ｗｅｓｔｅｒｎ 杂交检测肾皮质 Ｐ Ｄ Ｇ Ｆ Ｂｍ Ｒ Ｎ Ａ 及细胞膜 Ｐ Ｄ Ｇ Ｆβ受体蛋白表达。结果 苯那普利能降低糖尿病大鼠血肌酐、相对肾重及肾皮质 Ａ Ｃ Ｅ 活性。免疫组织化学结果提示苯那普利可抑制糖尿病肾皮质肾小球及肾小管Ⅳ型胶原、 Ｆ Ｎ 及 Ｐ Ｄ Ｇ Ｆ Ｂ 蛋白高表达； Ｎｏｒｔｈｅｒｎ 杂交表明肾皮质 Ｐ Ｄ Ｇ Ｆ Ｂ ｍ Ｒ Ｎ Ａ 表达比对照组增加近３ 倍， Ｗｅｓｔｅｒｎ 杂交证实肾皮质细胞膜 Ｐ Ｄ Ｇ Ｆβ受体蛋白表达比对照组增加近１ ．５ 倍。苯那普利对肾皮质 Ｐ Ｄ Ｇ Ｆ Ｂｍ Ｒ Ｎ Ａ 表达无明显影响，但它可明显抑制肾皮质细胞膜 Ｐ Ｄ Ｇ Ｆβ受体蛋白高表达。结论 苯那普利对糖尿病大鼠肾脏保护作用至少部分与抑制 Ｐ Ｄ Ｇ Ｆ?

Objective To investigate effects of Benazepril on the expression of PDGF B chain and its β receptor in diabetic rat renal cortex.Methods 20 rats were divided into control group (C),diabetic group(D) and diabetic+Benazepril group(DB).After 4 weeks of Benazepril treatment, ACE activities of plasma, renal cortex and medulla,were detected by fluorimetric assay; the expression of type Ⅳ collagen , fibronectin (FN) and PDGF B chain protein were determined by immunohistochemistry in renal cortex, and the expression of PDGF B chain mRNA and PDGF β receptor protein were measured by Northern and Western blot analysis in renal cortex and its cell membrane, respectively. Results Benazepril could decreased elevated serum creatinine lever,relative kidney weight and ACE activities in diabetic rats renal cortex. Immunohistochemistry showed that Benazepril could prevent overexpression of type Ⅳ collagen, FN and PDGF B chain protein within glomeruli and tubule of diabetic rats renal cortex.Compared with C group,the expression of PDGF B chain mRNA increased by 3 0 folds in renal cortex of D group from Northern blot and the expression of PDGF β receptor protein increased by 1 5 folds in cell membrane of renal cortex of D group from Western blot. Benazepril treatment had no effect on overexpression of PDGF B chain mRNA in diabetic rats renal cortex, however, it could significantly reduce increased expression of PDGF β receptor in cell membrane of diabetic rats renal cortex. Conclusion The protection of benazepril against kidney was associated, at least in part, with down regulating overexpression of PDGF B chain and PDGF β receptor protein in diabetic rats kidney cortex.