氯沙坦对糖尿病大鼠肾脏AT_2受体及细胞因子mRNA表达的影响

Effect of losartan on mRNA expression of type 2 angiotensin II receptor and cytokines in diabetic rats kidney

目的:研究氯沙坦对糖尿病大鼠肾脏AT2受体及细胞因子mRNA表达影响。方法:SD大鼠随机分成3组:对照组、糖尿病组、氯沙坦治疗组(30mg.kg-1.d-1,ig)。实验第8周,应用RT-PCR技术检测大鼠肾皮质血管紧张素Ⅱ2型受体(AT2)、转化生长因子-1β(TGF-β1)、血小板衍化生长因子-B(PDGF-B)、肿瘤坏死因子-α(TNF-α)及Ⅳ型胶原的mRNA表达。同时用放免法检测大鼠肾皮质血管紧张素II(Ang II)含量。结果:糖尿病大鼠尿蛋白排泄率(P<0.01)、肾皮质Ang II水平(P<0.05)较对照组明显升高;糖尿病组大鼠肾皮质TGF-β1、PDGF-B、TNF-α及Ⅳ型胶原的mRNA表达较对照组大鼠显著增加(P<0.01);然而,糖尿病组大鼠肾皮质AT2mR-NA表达却较对照组显著下降(P<0.05),氯沙坦治疗能明显降低糖尿病大鼠肾皮质TGF-β1、PDGF-B、TNF-α及Ⅳ型胶原的mRNA表达(均P<0.05)。治疗组AT2的mRNA表达则明显高于对照组(P<0.05)与糖尿病组(P<0.01)。结论:糖尿病大鼠肾皮质AT2受体mRNA表达的下调可能与肾组织TGF-1βP、DGF-B、TNF-α及血管紧张素Ⅱ表达的增加有关。氯沙坦激活AT2受体的表达的机制可能与下调肾脏系列细胞生长因子的表达有关。

AIM： To investigate the effect of losartan on the mRNA expression of type 2 angiotensin Ⅱ receptor and cytokines in diabetic rat kidney. METHODS： SD rats were randomly divided by following groups： control rats （group C）, diabetic rats （group D） and diabetic rats treated with losartan （ 30 mg·kg^-1·d^-1, by gavage, group DT）. At the end of 8-weeks study, mRNA expressions Of the type 2 angiotensin Ⅱ receptor （AT2）, transforming growth factor-β1 （TGF-β1）, platelet-derivedgrowth factor -B （ PDGF-B ）, tumor necrosis factor-α （TNF-α） and collagen Ⅳ in rats renal cortex were measured by RT-PCR, respectively. In addition, angiotensin Ⅱ level in renal cortex was determined by the radioimmunoassay. RESULTS： In group D, urine protein excretion （ P 〈 0. 01 ） and angiotensin Ⅱ level （ P 〈 0.05 ） in rats renal cortex were. increased obviously in contrast to group C. mRNA expressions of TGF-β1, PDGF-B, TNF-α and collagen Ⅳ （ P 〈 0.01 ） in diabetic renal cortex weremarkedly elevated in contrast to group C, too. However, mRNA expressions of AT2 in group D showed a significant decrease （ P 〈 0.05）. Administration of losartan markedly ameliorated urine protein excretion and mRNA expressions of TGF-β1, PDGF-B, TNF-α and collagen Ⅳ （ P 〈 0.05）, but increased AT2 mRNA expression obviously in contrast to group D. CONCLUSION： The decreasedmRNA expressions of AT2 in diabetic kidney may be related with elevated mRNA expressions of TGF-β1 , PDGF-B, TNF-α and angiotensin Ⅱ . Down-regulation of renal cytokines expression may involve in the mechanisms of upregulation expression of AT2 caused by losartan.