Abstract
As diabetic nephropathy (DN) is one of the most common and destructive microvascular complications of diabetes mellitus, the goal of this study, therefore, was to investigate the renal protective effect and latent mechanisms of Hirudo lyophilized powder on diabetic rats. In this study, all rats were randomly assigned into the control group and diabetic group. The rats of diabetic group were injected with low-dose STZ (35 mg/kg) intraperitoneal plus high-fat diet to induce diabetes. Then, the successful diabetic model rats were weighed and randomly assigned into four groups: (1) diabetic model group (DM group); (2) Hirudo lyophilized powder 0.3 g/kg treatment group (SL group); (3) Hirudo lyophilized powder 0.6 g/kg treatment group (SM group); (4) Hirudo lyophilized powder 1.2 g/kg treatment group (SH group). Their fasting blood glucoses (FBG) were measured every 4 weeks. After treatment with Hirudo lyophilized powder at a corresponding dose once a day for 16 weeks, their metabolic and biochemical as well as oxidative stress parameters were tested, and the kidney weight (KW)/body weight (BW) was calculated. The renal tissues were used for histological, mRNA, and protein expression analysis. The results showed that Hirudo lyophilized powder could protect against the structural damages and functional changes of diabetic renal tissue by inhibiting oxidative stress, inflammation, and fibrosis. Furthermore, it was found in the further research that inhibiting the NOX4 expression and JAK2/STAT1/STAT3 pathway activation might be the underlying mechanisms. Collectively, Hirudo lyophilized powder might be a promising therapeutic agent for the treatment of DN.
Highlights
Diabetes mellitus is an epidemic disease worldwide. e International Diabetes Federation reported that there were approximately 451 million diabetic patients worldwide in 2017, and the figure was expected to increase to 693 million by 2045 [1]
STZ injection combined with HFD in rats can simulate the characteristics of human type 2 diabetes and its complications, such as proteinuria, impaired renal function, glomerular hypertrophy, and glomerulosclerosis [20]
Low-dose intraperitoneal injection of STZ plus HFD treatment resulted in significant hyperglycemia, increasing the renal hypertrophy index, impairment of renal function (BUN, SCr), and elevation of urine protein excretion, as well as abnormal renal tissue structure in diabetic rats. ese data demonstrated that the diabetic nephropathy (DN) model rat was successfully established
Summary
Diabetes mellitus is an epidemic disease worldwide. e International Diabetes Federation reported that there were approximately 451 million diabetic patients worldwide in 2017, and the figure was expected to increase to 693 million by 2045 [1]. Diabetes mellitus is an epidemic disease worldwide. E International Diabetes Federation reported that there were approximately 451 million diabetic patients worldwide in 2017, and the figure was expected to increase to 693 million by 2045 [1]. Persistent hyperglycemia and long-term metabolic disorders will cause damage to multiple organs and tissues [2]. Diabetic nephropathy (DN), which seriously endangers human health, is one of the most common and destructive microvascular complications, and it is the primary cause of end-stage renal disease [3]. 20–40% of patients develop DN after the onset of diabetes [4]. Strict glycemic and blood pressure control constitute the mainstay of management for DN [3]. DN still occurs in a significant portion of diabetic patients. DN still occurs in a significant portion of diabetic patients. erefore, it may be useful and necessary to study therapies target for DN
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