中文摘要：

目的研究舒洛地特对糖尿病高血压大鼠的肾脏保护作用和足细胞podocalyxin（PCX）表达的影响。方法链脲佐菌素（STZ）注射后，醋酸脱氧皮质酮（DOCA）＋盐建立糖尿病高血压大鼠模型。设对照组（CTL组）、模型组（STZ＋DOCA组）、舒洛地特治疗组（GAG组）和舒洛地特＋替米沙坦治疗组（GAG＋ARB组），每组各6只大鼠。于建模后0、2、4、6和8周测尾动脉压、尿白蛋白和8周末尿N-乙酰-β-葡萄糖苷酶（NAG）。8周末取血检测胰岛素、血肌酐（Scr）、胆固醇（TC）、三酰甘油（TG）、Na^＋、K^＋。HE、PAS染色观察病理改变和。肾小球正切面足细胞计数。免疫组织化学检测podocalyxin在肾小球表达和分布。RT—PCR和Western印迹法检测podocalyxinmRNA和蛋白表达。结果（1）GAG＋ARB组4周末血压显著低于STZ＋DOCA组和GAG组（P〈0．05）。GAG组和GAG＋ARB组TG、TC和胰岛素与STZ＋DOCA组差异无统计学意义。（2）6周末GAG＋ARB组尿白蛋白量显著低于STZ＋DOCA组[（52．9±7．6）mg／24h比（102．2±6．9）mg／24h，P〈0．05]；8周末GAG组和GAG＋ARB组尿白蛋白量均显著低于STZ＋DOCA组（P〈0．05），而GAG＋ARB组尿白蛋白量显著低于GAG组[（33．8±6．8）mg／24h比（85．2±8．7）mg／24h，P〈0．05]。GAG＋ARB组和GAG组尿NAG均显著低于STZ＋DOCA组（P〈0．05）。（3）GAG组和GAG＋ARB组肾小球硬化指数（GSI）和间质纤维化指数（IF）均显著低于STZ＋DOCA组（P〈0．05），各组肾小球正切面足细胞数差异无统计学意义。（4）与STZ＋DOCA组相比，GAG组PCXmRNA和蛋白表达显著增加，而GAG＋ARB组PCX表达显著高于GAG组。结论舒洛地特可通过增加足细胞podocalyxin表达，减轻糖尿病高血压大鼠蛋白尿和病理损伤，与替米沙坦联用有叠加作用。

英文摘要：

Objective To explore the effect of sulodexide on renal injury and podoealyxin expression of podocytes in STZ diabetic desoxycorticosterone acetate （DOCA）-hypertensive rats. Methods Wistar rats were subjected to subcutaneous injection of streptozotoein（STZ）, followed by uninephreetomy and subcutaneous administration of DOCA. Diabetic and hypertensive rats were randomly allocated to treatment with sulodexide or a combination of sulodexide and telmisartan for 8 weeks. Blood pressure （BP）, 24-hour urinary albumin were measured every 2 weeks. Blood and urinary samples were collected to detect biochemical indexes of plasma and urinary β-acetyl-β-D-glucosaminidase （NAG） at the end of the study. Immunohistochemistry （IHC）, RT-PCR and Western blot were performed to examine the expression and distribution of podocalyxin. Results STZ ＋DOCA-treated rats progressively developed hypertension, albuminuria and hyperglycemia. Hyperlipidemia and hypoinsulinemia were found in diabetic and bypertensive rats compared with controls. Albuminuia was significantly reduced in sulodexide group at week 8 and sulodexide plus telmisartan group at week 6 and week 8. Blood pressure decreased in sulodexide plus telmisartan group. No significant effects on lipid and glucose metabolism were observed in all treated groups. Histopathological index increased in STZ＋DOCA- treated rats, but was significantly lower in sulodexide group as well as sulodexide plus telmisartan group. The number of podocytes on glomerular cross-section of the four groups were comparable. Segmental loss and down-regulation of podocalyxin were detected in STZ＋DOCA-treated rats, which were greatly attenuated by sulodexinde, meanwhile, combination treatment preserved more podocalyxin expression in glomeruli than snlodexide monotherapy. Conclusion Sulodexide effectively reduces albuminuria, prevents loss of podocyte podocalyxin and alleviates renal damage in STZ diabetic DOCA-hypertensive rats.