中文摘要：

目的探讨两种剂量胸腺素p4（thymosinp4，Tp4）对肾小管问质纤维化大鼠转化生长因子β（TGF—β）和结缔组织生长因子（CTGF）表达的影响，并进一步评估各组肾小管问质损伤和肾功能。方法应用单侧输尿管梗阻（UUO）手术建立大鼠模型。将健康成年的雄性SD大鼠随机分为4组，每组15只：假手术组（Sham组）、UUO模型组、低剂量组（UUO术后给予lmg／LTp4治疗）、高剂量组（UUO术后给予5mg／LTp4治疗）。模型组和Sham组术后给予等量生理盐水灌胃。观察术后第2周各组肾功能（24h尿蛋白量、尿素氮和血肌酐）和肾组织病理学改变，应用原位杂交和Western印迹分别检测肾小管间质中TGF—β、CTGF的mRNA和蛋白表达。结果与Sham组比较，模型组肾组织有高水平TGF-β、CTGFmRNA及蛋白表达均降低（均P〈0．01）；与模型组比较，两TS4组TGF—β和CTGF的mRNA、蛋白表达（均P〈0．01），高剂量组比低剂量组下降更明显（P〈0．05）。且TGF-β mRNA表达与CTGFmRNA表达呈正相关（r=0．697，P〈0．01）。模型组大鼠24h尿蛋白量及肾小管间质损伤面积比Sham组明显增加；TB4能改善这种肾脏损害，TIM组24h尿蛋白量及肾小管间质损伤面积均低于模型组，而且高剂量组比低剂量组的效果更显著（均P〈0．05）。各组血肌酐及血尿素氮差异无统计学意义。结论TB4可能以剂量依赖的方式抑制肾问质纤维化大鼠肾脏TGF-β／CTGF表达，从而发挥肾脏保护作用。

英文摘要：

Objective To investigate the influence of thymosin beta 4 （Tβ4） with two different dosages on the expression of transforming growth factor beta （TGF-β） and connective tissue growth factor （CTGF） in rats with renal tubular interstitial fibrosis, and to further estimate the changes of renal tubular interstitial lesions. Methods Rat models of renal tubular interstitial fibrosis were established by unilateral ureteral occlusion （UUO）. The male SD rats were randomly divided into 4 groups and 15 rats in each group： sham group, model group, treatment group with 1 mg/L Tβ4 and treatment group with 5 mg/L Tβ4. Rats in sham group and model group were poured into the same amount of saline. The renal function and renal pathological changes were observed after the second week. The mRNA and protein expression of TGF-β and CTGF in renal tissues was tested by in- situ hybridization and Western blotting. Results Compared with that in sham group, the expression of TGF-βmRNA and its protein, CTGF mRNA and its protein was significantly higher in model group （all P 〈 0.01）. Compared with rats of model group, TβA, treatment rats had lower mRNA and protein expression of TGF-β and CTGF （all P 〈 0.01）, and the expression in treatment group with 5 mg/L Tβ4 was lower than that in treatment group with 1 mg/L Tβ4 （P 〈 0.05）. And the expression of TGF-β mRNA was positively correlated with CTGF mRNA expression （r=0.697, P 〈 0.01）. The 24 h total urinary protein and the area of renal tubular interstitial lesion in model group were significantly more than those in sham group, and also more than those in T134 treatment group （all P 〈 0.05）. Tβ4 treatment attenuated kidney damage, and the effects in treatment group with 5 mg/L Tβ4 were better than those in treatment group with 1 mg/L Tβ4. No difference in serum creatinine and blood urea nitrogen was observed among 4 groups （all P 〉 0.05）. Conclusions Tβ4 treatment can inhibit the renal TGF-β and CTGF expression of rats with tubu