Aggravation of diabetic nephropathy in OLETF rats by Thy-1.1 nephritis.

ABSTRACT

OBJECTIVE: To clarify whether the induction of Thy-1.1 nephritis aggravates diabetic nephropathy in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, which is a model of diabetes mellitus. METHOD: Forty-week-old OLETF rats were divided into 2 groups according to treatment (1) 1 mg/kg body weight of OX7, an anti-Thy1.1 antibody (administered intravenously) (Group T, n = 14); (2) 0.9% saline (Group C, n = 14). The histological findings for the kidneys and the index of glomerulosclerosis (IGS) were determined 20 weeks after administration, and urine and serum chemistry were also assessed. The same procedure was performed as a control in 2 groups of Long-Evans Tokushima Otsuka (LETO) rats (i.e., nondiabetic OLETF rats). RESULTS: The urinary protein excretion values and the levels of serum albumin in the OX7-treated OLETF rats were significantly higher and lower than those in the untreated OLETF rats, respectively. Total cholesterol was significantly increased in the OX7-treated OLETF rats compared with the untreated OLETF rats. In the histological analysis, IGS was significantly higher in the OX7-treated OLETF rats than in the untreated OLETF rats. Neither deteriorations in the laboratory assessment values nor histological alterations were seen in the LETO rats. CONCLUSION: These findings indicate that an anti-Thy-1.1 antibody irreversibly aggravates diabetic nephropathy in the OLETF rat.