|
The purpose and significance:Diabetic nephropathy as a serious complication of diabetes, the incidence is rising, the method in the treatment of diabetic nephropathy in the past difficult to obtain satisfactory results. Oxidative stress is considered the key to the progress of diabetic nephropathy, many experimental studies suggest that raise antioxidant central part of the nuclear factor related to E2factor (Nrf2) to activate a variety of antioxidant enzymes, such as: heme-1(HO1), gamma-glutamine cysteine synthetase (gamma GCS), superoxide dismutase (SOD), delay the progress of diabetic nephropathy. But now applied to clinical antioxidants such as vitamin E and other limited, both animal experiments and clinical observation have little effect. So the other antioxidant drug treatment of diabetic nephropathy is particularly important.Methord:Parti: the Nrf2gene knockout (Nrf2-/-) and non knockout (Nrf2+/+) mice, were randomly divided into Nrf2-/-normal group, the Nrf2-group, the Nrf2+/+/-model group, the Nrf2normally+/+model group, intraperitoneal injection of injection of5consecutive days in50mg/kgSTZ, diabetic nephropathy in mice model was established. ChengMo mice were randomly divided into: Nrf2-/-STZ group (Nrf2-/-STZ) and Nrf2-/-mignonette, low dose group (Nrf2-/-LL) and Nrf2-/-mignonette, high dose group (Nrf2-/-LH), TBHQ (Nrf2-/-TBHQ); Nrf2+/+STZ group (Nrf2STZ+/+) and Nrf2+/+mignonette, low dose group (Nrf2+/LL) and Nrf2+/+mignonette, high dose group (Nrf2+/+LH), TBHQ (Nrf2+/+TBHQ). Dosing record during the mice weight, water quantity, blood sugar, protein excretion, of a day.10weeks after death to collect specimens of serum and kidney in mice. Determination of mice kidney weight/body weight, serum creatinine, blood clean on both sides, Serum creatinine, serum albumin, serum urea nitrogen, serum SOD, serum levels of r-GCS. With HE staining and PAS staining of renal pathology slice and evaluate renal pathological changes.Part2: Experiment: in vitro cultured glomerular mesangial cells, respectively give Luteolin and TBHQ intervention. Western bolt method to detect intracellular antioxidant Nrf2and HO-1the expression and secretion of change, using SPSS17.0statistical analysis.Results:Part1: Experiments on animals1) Nrf2:-/-mice, LL, LH group and STZ group of TBHQ group blood sugar, urine protein, water quantity, blood creatinine, blood urea nitrogen significantly higher than the control group, weight gain significantly slower than control group, serum albumin is lower than the control group, kidney pathological changes compared with the control group, no difference between the above four groups, serum SOD, gamma GCS expression in each group had no difference.2) Nrf2+/+mice:STZ group, LL, LH, TBHQ group blood sugar, urine protein, water content, serum creatinine, blood urea nitrogen significantly higher than the control group, the blood sugar level no obvious differences between the four groups, urine protein levels, water content, serum creatinine and blood urea nitrogen level of LH group and TBHQ was lower than that in STZ group;, LL, LH group and STZ group of TBHQ weight increased slowly in the control group, and group but LL, LH, TBHQ group weight grow slightly faster in the STZ.Part2:Luteolin and TBHQ can raise Nrf2in cultured glomerular mesangial cells in vitro and the expression of HO1, which raised Nrf2mignonette element expressions are dose dependent.Conclusions:Luteolin can increase antioxidant enzymes SOD Nrf2activation, the expression of HO1, gamma, GCS, of STZ induced diabetic nephropathy in mice kidney protection.
|