目的观察小檗碱(berberine,BBR)对糖尿病肾病(diabetic nephropathy,DN)大鼠肾脏的保护作用。方法采用高糖高脂饲料联合低剂量(35 mg·kg^-1)链脲佐菌素(streptozotocin,STZ)诱导糖尿病肾病大鼠模型。随机分为空白对照组、模型组、BBR(50 mg·kg^-1)、BBR(100 mg·kg^-1)和BBR(200 mg·kg^-1)剂量治疗组结果。分别在给药2、4、6、8周时检测大鼠空腹血糖变化,给药8周后测定大鼠血肌酐和尿素氮含量,尿总蛋白含量的变化;PAS染色观察DN肾脏组织病理学改变;免疫组织化学法检测肾脏组织血管内皮生长因子表达;Western blot法检测DN肾脏组织血管内皮生长因子表达水平。结果与正常对照组相比,模型组血糖及尿总蛋白指标明显升高,产生明显的形态学异常变化,同时血管内皮生长因子的表达量明显升高;与模型组相比,小檗碱给药组大鼠血糖和尿总蛋白量均明显下降;同时血液指标血肌酐和尿素氮水平也不同程度的下降;另外,BBR给药组还可明显改善糖尿病肾病大鼠肾脏病理学异常,降低肾脏血管内皮生长因子的表达。结论小檗碱可明显改善糖尿病肾病大鼠发病过程中的生化指标和肾脏病理损伤,这可能与其影响糖尿病肾病状态下肾脏组织中血管内皮生长因子的表达有关。
Aim To investigate the renoprotective effect of berberine in diabetic nephropathy rat model. Methods The rat model of DN was induced by intra-peritoneal injection of streptozotocin ( STZ ) after fed with high sugar and high fat diet for six weeks. The rats were divided into 5 groups randomly, i. e. normal control group, model group, BBR ( 50 mg · kg^-1 ) , BBR ( 100 mg · kg^-1 ) and BBR ( 200 mg · kg^-1 ) treatment group. The fasting blood glucose ( FBG) was evaluated at 2, 4, 6,8 week respectively. The patho-logical changes in the kidney were determined by PAS staining. The expression of vascular endothelial growth factor ( VEGF) was detected by immunohistochemistry and Western blot respectively. Results Compared with normal control group, the value of FBG, SCr, BUN and UTP of model group were sharply increased. Compared with model group, the value of FBG in ber-berine different dosage treatment groups were signifi-cantly decreased to various degrees, and berberine dif-ferent dosage treatment could decrease the levels of SCr, BUN and UTP in different degree. Berberine could surpress the alterations of pathological changes in the kidneys and downregulate the expression levels of VEGF in the kidney of diabetic rats with nephropathy. Conclusion Berberine could significantly ameliorate the biochemical indicators and renal injury of the model rats through affecting the abnormal expression levels of VEGF in the kidney.