| ObjectiveThe objective of this study was to evaluate the relation between expressions of hypoxia-inducible factor-1alpha(HIF-1α)and vascular endothelia growth factor(VEGF)in renal tissues and renal structural and functional lesions in type 2 diabetic rats and to observe the effects of Piogitazone, Dan-shen injection and Dan-shen dripping pill on the expressions of HIF-1αand VEGF,so as to reveal their possible renoprotective effects.MethodsAfter adaptive feeding for 1-week, specific pathogen free male SD rats were randomly divided into normal control group and model group.The rats of normal group(NC group) were administrated with normal diet.The rats of model group were fore-administrated with high-carbonhydrate-fat diet for 4-week,and then injected with 30mg/kg streptozotocin(dissolved in the 0.1mmol·L-1 citrate buffer solution) for once. After 72 hours, measured randomly blood glucose in tail venous and selected the one which blood glucose was equal or above 16.7mmo1·L-1 into experimental groups. Then the model rats were further randomly divided into four groups: type 2 diabetic group (DM group),Pioglitazone group(PIO group, 4 mg·kg-1·d-1 ), Dan-shen injection group (DSZ group, 12.5ml·kg-1·d-1),Dan-shen dripping pill group (DSP group, 500 mg·kg-1·d-1). The rats of treatmental groups were performed by intragastric administration for 8 weeks. The rats of NC group and DM group were performed by intragastric administration with equivalent distilled water for 8 weeks. Before the rats were sacrificed, we collected 24 hours urine for measurement of 24h urinary albumin excretion, blood samples were taken from inferior vena cave,the fasting blood glucose,fasting serum insulin, HOMA-insulin resistance,serum creatinine,blood urea nitrogen,triglyceride,total cholesterol,low density lipoprotein cholesterol,high density lipoprotein cholesterol,superoxide dismutase and malondialdehyde were dectected.Kidneys were removed and weighted,to calculate the ratio of kidney weight vs body weight (KW/BW) . Put the kidney into 10% formalin to be fixed and made paraffinslices. Observed the pathological changes of the kidneys and studied the expressions of HIF-1αand VEGF in renal tissues with method of immunobloting.ResultsThe combination of high-carbonhydrate-fat diet feed and intraperitoneal injection low-dose STZ could successfully induce the rats model of type 2 Diabetes Mellitus.Compared with NC group, the concertration of fasting plasma glucose, fasting serum insulin,HOMA-insulin resistance, total cholesterol, triglyceride, low density lipoprotein cholesterol, serum creatinine, blood urea nitrogen, 24h urinary albumin excretion, the ratio of KW/BW,extracellular matrix accumulation index,superoxide dismutase,malondialdehyde and the expressions of HIF-1αand VEGF in renal tissue of DM group were significantly increased (P<0.01), the concentration of high density lipoprotein cholesterol in DM group was decreased(P<0.01).Compared with DM group,the concentration of fasting plasma glucose,fasting serum insulin,HOMA-insulin resistance, total cholesterol,triglyceride, low density lipoprotein cholesterol,serum creatinine,blood urea nitrogen,plasma malondialdeh- yde,24h urinary albumin excretion,the ratio of KW/BW,extracellular matrix accumulation index, and the expressions of HIF-1αand VEGF in renal tissue of PIO group, DSZ group and DSP group were significantly decreased(P<0.05,P<0.01). The concentration of high density lipoprotein cholesterol in PIO group,DSZ group and DSP group were no significantly difference with DM group(P>0.05).Compared with DM group, the concentration of malondialdehyde and the enzyme activity of superoxide dismutase were significantly decreased in PIO group,DSZ group and DSP group,as well as the expressions of HIF-1αand VEGF in renal tissues,but Dan-shen injection had less effects than Dan-shen dripping pill and Pioglitazone.Compared with DM group,the rats'renal pathology of three therapeutical groups showed significantly improving(P<0.01),there were no significance on the improving of Diabeitc rats'renal pathology among PIO group,DSZ group and DSP group(P>0.05).Conclusions1.The 24h urinary albumin excretion and glomeruli ECM were significantly increased in type 2 Diabetic rats and they were positively related with expressions of HIF-1αand VEGF in renal tissues of type 2 diabetic rats.2.The drugs of Pioglitazone, Dan-shen injection and Dan-shen dripping pill could reduce the concentration of fasting plasma glucose, fasting serum insulin, HOMA-insulin resistance,total cholesterol,triglyceride,low density lipoprotein cholesterol, increase the enzyme activity of superoxide dismutase,reduce the concentration of malondialdehyde,reduce 24h urinary albumin excretion, inhibit the expressions of HIF-1αand VEGF in renal tissues.It suggests that the drugs of Pioglitazone,Dan-shen injection and Dan-shen dripping pill could improve glucolipid metabolism,insulin resistance and reduce oxidative stress in type 2 diabetic rats.Thus they exerts the actions through regulating hypoxia response pathyway, which may have benefits on diabetic nephropathy.
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