Expressions of NF-κB and downstream inflammatory factors in the kidney of insulin resistance rat / 解放军医学杂志

ABSTRACT

Objective To investigate the variation and significance of the expressions of NF-kB, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the renal tissue of insulin-resistant rat. Methods Thirty healthy male Wistar rats were bred since 2 months old, and they were randomly divided into normal control (NC) group (n=15) and insulin-resistant (IR) group (n=15). Insulin resistance rat model was reproduced by feeding with high fat and sucrose diet. Hyperinsulinemic-euglycemic clamp test was used to verify the reproduction of the model. The kidneys of the rats were obtained after the successful reproduction of the model. The change in renal histology was observed by HE staining, and the expressions of iNOS and COX-2 in the kidneys were detected by immunohistochemistry staining. The mRNA expressions of NF-κB, iNOS and COX-2 in the kidneys were assessed with RT-PCR. DNA binding activity of NF-κB in the rat's kidney was assessed with electrophoretic mobility shift assay (EMSA). Results HE staining showed that, compared with NC group, the early lesions of the renal tissue, such as glomerular enlargement and mesangial region broadening, could be seen in IR group. Immunohistochemical staining showed that the positive expressions of iNOS and COX-2 were up-regulated significantly in IR group than in NC group (P<0.05). RT-PCR revealed that the expressions of NF-κB mRNA, iNOS mRNA and COX-2 mRNA in renal tissue were significantly higher in IR group than in NC group (P<0.05). EMSA showed that the binding activity of NF-κB in renal tissue increased significantly in IR group than in NC group (P<0.05). Conclusion NF-κB activation is present in the kidney tissue in the insulin resistance rat, which may upregulate the expression of downstream target gene iNOS and COX-2, resulting in damage to kidney tissue. The activation of NF-κB maybe one of the initiative factors that lead to the kidney lesion of the insulin resistance rat.