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目的 探讨选择性环加氧酶 2抑制剂莫比可对糖尿病大鼠肾脏病变的影响。方法 将大鼠分成正常对照组 (6只 )、不用药组 (8只 )、消炎痛组 (6只 )和莫比可组 (9只 )。 16周后放射免疫法测定大鼠尿液中前列腺素E2 (PGE2 )和血栓烷素B2 (TXB2 )的排泄量 ,应用逆转录 聚合酶链式反应和免疫沉淀的方法分别检测肾皮质中转化生长因子 β1(TGF β1)及其Ⅱ型受体 (TβR2 )的基因表达和血管紧张素Ⅱ 1型受体 (AT1R)的蛋白水平 ,并观察PAS染色下肾脏的病变情况。结果 与正常对照组相比 ,糖尿病大鼠PGE2 和TXB2 排泄增多 (分别为 16 4 1pg/ 2 4h± 2 88pg/ 2 4h ,5 5 0 7pg/ 2 4h± 135 9pg/ 2 4h)。TGF β1和TβR2 的基因表达显著上调 ,分别为 0 185± 0 0 37,0 194± 0 0 5 4。AT1R的蛋白水平下降 2 1 3%。光镜显示肾小球系膜区增宽 ,PAS染色阳性的胶原沉积增多。消炎痛、莫比可均能不同程度地减少PGE2 的生成 (P <0 0 5 ) ,但TXB2 仅在莫比可组显著下降。莫比可组TGF β1和TβR2 基因表达明显下调 (39% ,4 7% ) ,AT1R的蛋白水平回升 (P <0 0 5 ) ,肾脏病变有所好转 ,而消炎痛无效。结论 莫比可对糖尿病肾脏病变具有一定的保护作用 ,其机制可能与调节TGF β1和AT1R有关
Objective To investigate the effect of selective cyclooxygenase 2 inhibitor moyiben on renal lesions in diabetic rats. Methods The rats were divided into normal control group (n = 6), untreated group (n = 8), indomethacin group (n = 6) and metoprolol group (n = 9). Twenty-six weeks later, the excretion of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) in urine of rats were measured by radioimmunoassay. The transdifferentiation of renal cortex was detected by reverse transcription polymerase chain reaction and immunoprecipitation (TGFβ1) and its type Ⅱ receptor (TβR2) gene and angiotensin Ⅱ type 1 receptor (AT1R) protein levels were observed, and renal lesions under PAS staining were observed. Results Compared with the normal control group, the excretion of PGE2 and TXB2 in diabetic rats increased (16 4 1 pg / 2 4h ± 2 88 pg / 2 4h and 5 507 pg / 2 4h ± 135 9 pg / 2 4h, respectively). The gene expressions of TGFβ1 and TβR2 were significantly up-regulated, which were 0 185 ± 0 0 37,0 194 ± 0 054, respectively. AT1R protein levels decreased by 21.3%. Light microscopy showed mesangial area widened, PAS staining positive collagen deposition increased. Indomethacin and modifile could all reduce the production of PGE2 to some extent (P <0.05), but TXB2 decreased only in the group of Mobil. The expression of TGFβ1 and TβR2 genes was significantly down-regulated (39%, 47%) in model group, while the protein level of AT1R was up (P <0 05). Renal lesions improved and indomethacin was ineffective. Conclusions Mobil can protect diabetic nephropathy, and its mechanism may be related to the regulation of TGFβ1 and AT1R