洛沙坦对大鼠糖尿病模型肾脏转化生长因子βⅠ型、Ⅱ型受体表达的影响

Losartan downregulates the expression of transforming growth factor -β type Ⅰ and type Ⅱ receptors in kidney of diabetic rat

目的 观察洛沙坦对大鼠糖尿病模型肾脏转化生长因子 βⅠ型受体 (TGFβRⅠ )、Ⅱ型受体 (TGFβRⅡ )表达的影响。 方法 30只大鼠按体重随机分为 3组 ,每组 10只。A组 :健康对照组 ;B组 :糖尿病模型组 ,尾静脉注射链脲佐菌素 5 0mg/kg体重制成糖尿病模型 ;(3)C组 :洛沙坦治疗组 ,按B组方法建立大鼠糖尿病模型后第 2天给予洛沙坦 10mg·kg体重 -1·d-1灌胃。 8周后半定量逆转录 聚合酶链反应检测 3组肾皮质TGFβRⅠ、TGFβRⅡ和纤维连接蛋白 (FN)mRNA的表达。免疫组化测 3组肾皮质TGFβRⅠ、TGFβRⅡ和FN蛋白的表达。生化法测血糖、尿素氮和肌酐水平。放射免疫法测血胰岛素和血管紧张素Ⅱ。磺基水杨酸法测 2 4h尿蛋白。结果 B组大鼠平均肾小球体积、肾重 /体重增加 ,2 4h尿蛋白、血尿素氮和肌酐水平上升 (P <0 0 5 ) ;肾皮质TGFβRⅠ、TGFβRⅡ、FNmRNA和蛋白表达显著增加 (P <0 0 5 )。C组大鼠平均肾小球体积、肾重 /体重减少 ,2 4h尿蛋白、血尿素氮和肌酐水平下降 (P <0 0 5 ) ;肾皮质TGFβRⅠ、TGFβRⅡ、FNmRNA和蛋白表达显著降低 (P <0 0 5 )。 结论 洛沙坦下调大鼠糖尿病模型肾脏TGFβRⅠ、TGFβRⅡ的表达 ,抑制肾脏细胞肥大 ,减少细胞外基质成分的合成。

Objective To investigate the influence of losartan on the expression of transforming growth factor-β type Ⅰ and type Ⅱ receptors(TGFβRⅠ, TGFβRⅡ) in kidney of diabetic rat model. Methods The Wistar rats were randomly divided into 3 groups with 10 rats in each group: normal control group(group C), diabetic rat model group (group DM, the model was reproduced by intravenous injection of 50 mg/kg streptozotocin), and the group of diabetic rat model treated with losartan (group DL, 10 mg· kg -1 · d -1 of losartan intragastrically since the 2nd day of streptozotocin injection). Eight weeks later, the mRNA and protein expressions of TGFβRⅠ, TGFβRⅡ and fibronectin in renal cortices of all 3 groups were measured by semiquantitative reverse transcription-polymerase chain reaction and by histoimmunochemical methods. The blood glucose , urea and creatinine were detected by biochemical assay and the blood insulin and angiotensin Ⅱ by radioimmunoassay. The urine albumin excretion ratio was examined by sulfosalicylic acid assay. Results The mean glomerular volume, kidney weight/body weight ratio, urine albumin excretion ratio, blood urea and creatinine were significantly elevated in group DM than that in group C( P <0.05). The mRNA and protein expressions of TGFβRⅠ, TGFβRⅡ and fibronectin in renal cortices of group DM were significantly increased than that in group C as well( P <0.05).The increase in mean glomerular volume, kidney weight/body weight ratio, urine albumin excretion ratio, blood urea and creatinine in group DL was significantly attenuated as compared to group DM. The mRNA and protein expressions of TGFβRⅠ, TGFβRⅡ and fibronectin in renal cortices of group DL were also significantly reduced as compared to that in group DM( P <0.05). Conclusion Losartan may have protective effects on the kidney of diabetic rat model. The mechanism of the protection might related to its downregulatory effect on the expression of TGFβ system, which inhibited the hypertrophy of kidney cells and reduced the synthesis of extracellurlar matrix.