Hawthorne leaf flavonoids prevent oxidative stress injury of renal tissues in rats with diabetic kidney disease by regulating the p38 MAPK signaling pathway.

ABSTRACT

Objectives: Diabetic kidney disease (DKD) is the primary microvascular complication of diabetes. The incidence rate of DKD has increased worldwide, and DKD has become one of the most important causes of end-stage renal disease. In this study, we aimed to investigate the effects of hawthorn leaf flavonoids (HLF) on oxidative stress injury of renal tissue in DKD rats, and elucidate their mechanism(s) of action. Methods: A total of 35 male Sprague Dawley rats were randomly divided into the control group (CON group) and model group. Rats in the model group were fed a diet containing high sugar and fat and were injected with streptozotocin (STZ) into the abdominal cavity to induce diabetes. Diabetic rats that showed >50% increase in 24 h urine volume and >30 mg of 24 h urine protein excretion were selected as DKD model rats. After DKD models were successfully established, model rats were randomly divided into the diabetic kidney disease group (DKD group), irbesartan group (IRB group), and hawthorn leaf flavonoids group (HLF group). All rats were sacrificed at 12 weeks (w) after DKD models were established. Body weight and 24 h urinary protein levels were measured at 4 w, 8 w, and 12 w, respectively. Blood was collected to measure the levels of urea nitrogen, creatinine, triglyceride, nitric oxide, malondialdehyde, and superoxide dismutase. Pathologic changes in renal tissue were examined by hematoxylin and eosin (H&E) and Masson staining. Protein expression of p38MAPK and p-p38MAPK was determined by immunohistochemistry. Results: Our data showed that HLFs improved the general condition and body weight, and reduced the levels of urinary protein in model rats. Rats in the DKD group had more serious pathological damage in the kidney when compared to rats in the HLFs group. In addition, rats in the HLF group had significantly lower levels of urea nitrogen, creatinine, triglyceride, and malondialdehyde, and significantly higher levels of nitric oxide and superoxide dismutase than rats in the DKD group. Furthermore, p38MAPK and p-p38MAPK protein levels were significantly higher in rats in the DKD group compared to rats in the HLF group. Conclusions: HLFs have a protective effect against DKD in rats. The underlying mechanism may involve the reduction of oxidative stress by inactivation of the p38MAPK signaling pathway in renal tissues.