Bao Yan, Jia Ru-han, Yuan Jun, Li Jing
Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, PR China.
Pharmacology. 2007;80(1):57-64. doi: 10.1159/000103232. Epub 2007 May 25.
To study whether rosiglitazone prevents the development of diabetic nephropathy through reduction of reactive oxygen species and its downstream signal transduction pathways.
The rats were intraperitoneally injected with streptozotocin to induce diabetes, meanwhile the rats in the therapeutic groups were given rosiglitazone (5 or 20 mg/kg/day) for 4 weeks by intragastric administration. Blood glucose, serum lipid and creatinine, urinary albumin excretion were measured. Malondialdehyde content, the activities of nuclear factor-kappaB (NF-kappaB), antioxidant enzymes including Cu-Zn SOD and GSH-Px in kidney were also measured. In addition, the mRNA and protein expression of MCP-1 were semiquantitatively determined with PT-PCR and immunohistochemical staining respectively.
No significant difference of blood glucose and lipid were found between diabetic rats and rosiglitazone treatment groups. The renal histopathology was improved significantly. The expressions of MCP-1 mRNA and protein, malondialdehyde level and the activity of NF-kappaB were decreased markedly in rats treated with high-dose rosiglitazone, but the activities of renal Cu-Zn SOD and GSH-Px increased significantly.
Rosiglitazone treatment prevented glomerular injury in diabetic rats, which was closely related with its roles of reducing reactive oxygen species, NF-kappaB activation and MCP-1 expression in the early phase of diabetic nephropathy.
研究罗格列酮是否通过减少活性氧及其下游信号转导通路来预防糖尿病肾病的发生发展。
给大鼠腹腔注射链脲佐菌素诱导糖尿病，同时治疗组大鼠通过灌胃给予罗格列酮（5或20毫克/千克/天），持续4周。测量血糖、血脂、肌酐、尿白蛋白排泄量。还测量肾脏中丙二醛含量、核因子-κB（NF-κB）活性、抗氧化酶包括铜锌超氧化物歧化酶（Cu-Zn SOD）和谷胱甘肽过氧化物酶（GSH-Px）的活性。此外，分别用PT-PCR和免疫组织化学染色半定量测定单核细胞趋化蛋白-1（MCP-1）的mRNA和蛋白表达。
糖尿病大鼠与罗格列酮治疗组之间血糖和血脂无显著差异。肾脏组织病理学明显改善。高剂量罗格列酮治疗的大鼠中，MCP-1 mRNA和蛋白表达、丙二醛水平及NF-κB活性显著降低，但肾脏Cu-Zn SOD和GSH-Px活性显著增加。
罗格列酮治疗可预防糖尿病大鼠的肾小球损伤，这与其在糖尿病肾病早期减少活性氧、NF-κB激活和MCP-1表达的作用密切相关。
