| Objective:To study the protective effects of Naja naja atra venom on diabetic nephropathy(DN) model rats.Methods:The DN model rats were induced by intraperitoneal injection streptozotocin (STZ). Model rats were randomly divided into a diabetic group(n=8), and three treatment groups that received Naja naja atra venom30,90,270μg/kg/day via oral gavage. Another eight rats were used as normal group. After12weeks, all rats were sacrificed and the biological index levels in serum and urine were determined by colorimetric assay. Renal tissues were sliced for pathological observation and immunohistochemistry, pancreas tissues were sliced for pathological observation.Results:(1)The levels of glucose (Glu), urinary protein(PRO-U), serum creatinine(Scr), blood urea nitrogen(BUN), malondialdehyde(MDA), superoxide dismutase(SOD) total cholesterol(TC), triglycerides(TG), high-density lipoprotein cholesterol(HDL), transformation growth factor-β1(TGF-β1), nucleus factor-KappaB(NF-kB), albumin(ALB) had significant changed compare with normal rats(P<0.001), pancreas islet pathology revealed islet atrophy and inflammatory cells infiltration, kidney pathological showed the renal tubular degeneration after injection STZ.(2)The levels of GLU were down by22.91%,31.04%,27.89%after Naja Naja atra venom30,90,270μg/kg/day treatment(versus model rats P<0.05), islet damage ameliorated, inflammatory cells reduced.(3)The levels of PRO-U were significantly lower than the model group after Naja Naja atra venom treatment(P<0.05), and the concentration of ALB in treatment group increased respectively1.64%,5.55%,5.78%(90μg/kg/day versus model P<0.01,270μg/kg/dayversus model P<0.001).(4)The levels of BUN were significantly lower than model rats(P<0.05, P<0.01, P<0.05, respectively). Scr concentration were down by22.92%,19.83%,19.29%compare with model rats, respectively(P<0.001, P<0.001, P<0.01), the level of Ccr increased, especially90μg/kg/day versus model P<0.05. (5)The group glomerular volume of treatment group were down by8.15%,8.29%,6.75%compare with model group(30,90μg/kg/day versus model P<0.05). Pathological observation treatment group renal tubular degeneration were alleviated.(6)The MDA concentration of kidney tissues were fell by9.39%,22.56%,20.39%after Naja Naja atra venom treatment(90,270μg/kg/day versus model P<0.05). The SOD concentration were up by16.49%,15.46%,8.25%(30μg/kg/day versus model P<0.05,90μg/kg/day versus model P<0.01).(7)The concentrations of TC and TG were reduced after Naja Naja atra venom treatment(90μg/kg/day versus model P<0.05), HDL concentrations had significant increase compare with model rats P<0.05.(8)The distribution of NF-kappaB and TGF-(31in renal tubular epithelial cells were reduced after Naja Naja atra venom treatment, half quantitative results show:the NF-kappa B were down by3.61%,5.15%,4.64%(90,270μg/kg/day versus model P<0.05). TGF-β1were reduced by6.19%,6.70%,4.64%(30,90μg/kg/day versus model P<0.05)Conclusion:(1)Injection STZ (55mg/kg) can cause injection rat Glu levels increase, renal function disorder, pancreas and kidney pathological change, establish DN model, which can cause oxidatie stress, inflammatory reaction and lipid metabolic abnormalities.(2)The levels of Glu, PRO-U, kidney function indexs(Scr, BUN, Ccr), oxidative stress indexs(MDA, SOD), inflammation indexs(NF-kappaB, TGF-β1), lipid index indexs(TC, TG, HDL) were significantly improved, islet and kidney structures markedly ameliorated after treatment, which show Naja Naja atra venom can lower blood sugar, suppress oxidatie stress, regulating lipid metabolism, limit inflammation, improve renal function, delayed diabetes development process, reduce the incidence of DN. Naja Naja atra venom90μg/kg/day dose has more obvious treatment effect. |
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