Effects of high?fat diet feeding time on the establishment of a rat model of type 2 diabetic nephropathy / 中国实验动物学报

ABSTRACT

Objective To investigate the effects of different high-fat diet feeding time durations on blood glucose (BG), insulin resistance index(HOMA-IR), and urinary albumin excretion rate(UAER)in rats with high fat diet-induced type 2 diabetic nephropathy(DN). Methods Unilateral renal artery ligation, high-fat diet(throughout the ex-periment period),and low dose streptozotocin(STZ)intraperitoneal injection were used to establish a type 2 DN rat mod-el. After the operation,rats in the DN1 and DN2 groups received an intraperitoneal injection of STZ 30 mg/kg after 4 and 8 weeks of high-fat diet feeding,respectively. UAERs of the DN1 and DN2 groups were compared at 4 weeks after the STZ injection and the end of study(EOS). BG,body weight,HOMA-IR,kidney index,and pathological changes of the kidney were observed. Results UAER was increased in both groups at 4 weeks after the STZ injection,but significantly higher in the group DN2 than in the DN1 group(P<0.01). At the end of study(the 12th week),the renal tissues showed patho-logical changes,including glomerular capillary loop hypertrophy,increased mesangial matrix,and decreased capsule space in both groups. Compared with the DN1 group,the body weight was significantly higher(P<0.01),kidney index was sig-nificantly lower(P<0.01),while BG,serum insulin level,HOMA-IR,and UAER were no significantly changed in the DM2 group(P>0.05,respectively). Conclusions The results show that extending the feeding time of high-fat diet can aggravate the kidney damages in diabetic rats,but it can also delay the start of any planned intervention. Therefore,the ex-perimental protocol should be carefully designed based on the study objective.