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目的研究不同剂量盐酸吡格列酮(PIO)对链脲霉素诱导的糖尿病大鼠肾脏足细胞的保护及其与抗炎作用的关系。方法将SD大鼠随机分为正常对照组(NC组)、糖尿病组(DM组)、糖尿病低剂量PIO组(DR1组)、糖尿病中剂量PIO组(DR2组)和糖尿病高剂量PIO组(DR3组)。于0、8周末测尿白蛋白、尿Nephrin、尿单核细胞趋化因子-1(MCP-1)和尿肌酐(UCr),并计算尿白蛋白/肌酐(UACR)、Nephrin/肌酐(UNER)和MCP-1/肌酐(UMCR)。每周监测血糖(BG),8周末取血测糖化血红蛋白(HbA1c),留取左肾免疫组化检测肾组织Nephrin及MCP-1蛋白表达。结果①糖尿病大鼠各时间点BG及8周末HbA1c显著高于NC组(P<0.05),糖尿病大鼠组间差异无统计学意义。②8周末,各PIO组UACR、UNER和UMCR均显著低于DM组(P<0.05),且DR2、DR3组低于DR1组(P<0.05);肾脏Nephrin蛋白表达:NC组>各PIO组>DM组(均P<0.05),DR1、DR2和DR3组间差异无统计学意义;肾脏MCP-1蛋白表达:DM组>各PIO组>NC组(均P<0.05),DR1、DR2和DR3组间差异无统计学意义。③UNER与UMCR呈显著正相关(r=0.729,P<0.01),肾脏Nephrin蛋白与MCP-1蛋白呈显著负相关(r=-0.696,P<0.01)。结论吡格列酮对糖尿病大鼠足细胞有一定的保护作用,该作用可能与减轻局部炎症反应有关,并具有一定的剂量依赖性。
Objective To study the protective effects of pioglitazone hydrochloride (PIO) on renal podocytes in streptozotocin-induced diabetic rats and its relationship with anti-inflammatory effects. Methods SD rats were randomly divided into normal control group (NC group), diabetic group (DM group), diabetic low dose PIO group (DR1 group), diabetic middle dose PIO group (DR2 group) and diabetic high dose PIO group group). Urinary albumin, urinary Nephrin, MCP-1 and UCr were measured at 0 and 8 weeks. Urinary albumin / creatinine (UACR), Nephrin / creatinine ) And MCP-1 / creatinine (UMCR). Blood glucose (BG) was monitored every week. HbA1c was measured at the end of 8th week. Nephrin and MCP-1 protein expression in renal tissue was detected by immunohistochemistry. Results ① The levels of BG in the diabetic rats and HbA1c in the 8th week were significantly higher than those in the NC group (P <0.05). There was no significant difference between the diabetic rats. ② At the end of the 8th week, the UACR, UNER and UMCR in PIO group were significantly lower than those in DM group (P <0.05), and those in DR2 and DR3 group were lower than those in DR1 group (P <0.05); Nephrin protein expression in kidney: NC group> PIO group> DM group (all P <0.05). There was no significant difference between DR1, DR2 and DR3 groups. The expression of MCP-1 protein in DM group> PIO group> NC group (all P < No significant difference between groups. There was a significant positive correlation betweenUNER and UMCR (r = 0.729, P <0.01). There was a significant negative correlation between Nephrin protein and MCP-1 protein in kidney (r = -0.696, P <0.01). Conclusion Pioglitazone can protect the podocytes of diabetic rats. This effect may be related to the reduction of local inflammatory response and dose-dependent.