The First Affiliated Hospital of SooChow University, Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Soochow University School of Medicine, Suzhou 215006, Jiangsu, China.
Biomed Environ Sci. 2012 Dec;25(6):630-8. doi: 10.3967/0895-3988.2012.06.004.
To study the protective effects of naja naja atra venom (NNAV) in a rat model of diabetic nephropathy (DN).
The rat diabetes model was induced by intraperitoneal injection of streptozotocin (STZ). Thirty-two model rats were randomly divided into one DN group (n=8) and three treatment groups (n=8 each) that received NNAV at doses of 30, 90, or 270 μg/(kg·day) via oral gavage, another eight rats as normal controls. After 12 weeks, all rats were sacrificed and the changes in serum and urine biological index levels were determined by colorimetric assay. Microalbumin (mALB), N-acetyl-β- glucosaminidase (NAG) and cystatin C (CysC) concentrations were measured by ELISA. Renal tissues were sliced for pathological and immunohistochemical observations.
Comparied with the DN group, serum glucose was decreased by 31.04%, total cholesterol 21.96%, triglyceride 23.78%, serum creatinine 19.83%, blood urea nitrogen 31.28%, urinary protein excretion 45.42%, mALB 10.42%, NAG 20.65%, CysC 19.57%, whereas albumin increased by 5.55%, high-density lipoprotein-cholesterol 59.09%, creatinine clearance 19.05% in the treatment group by NNAV administration at dose of 90 μg/(kg·day). NNAV also reduced the levels of malondialdehyde in serum (22.56%) and kidney tissue (9.79%), and increased superoxide dismutase concentration in serum (15%) and decreased it in renal tissue (8.85%). In addition, under light microscopy kidney structure was improved and glomerular hypertrophy decreased by 8.29%. As shown by immunohistochemistry, NNAV inhibited transforming growth factor-β1 by 6.70% and nuclear actor-κB by 5.15%.
NNAV improves biological indexes in DN, and it may exert renoprotective effects in rats with STZ-induced diabetes.
研究中华眼镜蛇毒（NNAV）在糖尿病肾病（DN）大鼠模型中的保护作用。
采用腹腔注射链脲佐菌素（STZ）诱导大鼠糖尿病模型。32 只模型大鼠随机分为 1 只 DN 组（n=8）和 3 个治疗组（n=8），分别给予 NNAV 30、90 或 270μg/（kg·d）灌胃，另 8 只大鼠作为正常对照组。12 周后处死所有大鼠，通过比色法测定血清和尿液生物指标水平的变化。通过 ELISA 法测定微量白蛋白（mALB）、N-乙酰-β-氨基葡萄糖苷酶（NAG）和胱抑素 C（CysC）的浓度。肾组织切片行病理和免疫组化观察。
与 DN 组相比，NNAV 治疗组血清葡萄糖降低 31.04%，总胆固醇降低 21.96%，三酰甘油降低 23.78%，血清肌酐降低 19.83%，血尿素氮降低 31.28%，尿蛋白排泄降低 45.42%，mALB 降低 10.42%，NAG 降低 20.65%，CysC 降低 19.57%，白蛋白升高 5.55%，高密度脂蛋白胆固醇升高 59.09%，肌酐清除率升高 19.05%。NNAV 还降低了血清（22.56%）和肾组织（9.79%）中丙二醛的水平，增加了血清中超氧化物歧化酶的浓度（15%），并降低了肾组织中的浓度（8.85%）。此外，在光镜下，肾脏结构得到改善，肾小球肥大减少了 8.29%。免疫组化结果显示，NNAV 抑制转化生长因子-β1 表达 6.70%，核因子-κB 表达 5.15%。
NNAV 改善了糖尿病肾病的生物指标，可能对 STZ 诱导的糖尿病大鼠具有肾保护作用。
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