目的 观察小檗碱(berberine,BBR)对糖尿病肾病(diabetic nephropathy,DN)大鼠病程中肾脏的保护作用。方法 采用高糖高脂联合低剂量链脲佐菌素(streptozocin,STZ)诱导糖尿病肾病大鼠模型,并随机分为正常对照组、模型组、3个不同剂量小檗碱给药组、辛伐他汀、二甲双胍阳性药对照组。分别在给药2,4,6,8周时检测大鼠空腹血糖、血脂的变化;HE染色法观察糖尿病肾病病程中肾脏组织形态学改变;免疫组化法检测肾脏转化生长因子β1(TGF-β1)的表达;酶联免疫吸附实验检测肾脏白细胞介素-18(IL-18)的表达。结果 与模型组相比,小檗碱给药组大鼠空腹血糖、甘油三酯、总胆固醇、低密度脂蛋白胆固醇均明显下降,而高密度脂蛋白胆固醇明显升高;另外,小檗碱给药组还可明显改善糖尿病肾病大鼠肾脏形态学异常,降低肾脏转化生长因子-β1和白细胞介素-18的表达。结论 小檗碱可明显改善糖尿病肾病大鼠病程中的肾脏损害,这可能与其下调肾脏转化生长因子-β1和白细胞介素-18的表达有关。
OBJECTIVE To investigate the effect of berberine in different stages of diabetic nephropathy rat model. METHODS The rat model of diabetic nephropathy was induced by intraperitoneal injection of streptozocin (STZ) after feding with high sugar and high fat diet for six weeks. The rats were divided into 7 groups at random, ie normal control group, model group, 5 berberine treatment groups, diabetic rats treated with simvatastin and metformin served as positive control groups. The fasting blood-glucose (FBG) and blood lipid were evaluated at 2, 4, 6, 8 weeks respectively. The pathological changes in the kidney were determined by HE staining. The expression of transforming growth factor (TGF) -β1 and interleukin-18 ( IL-18 ) were detected by immunohistochemistry and ELISA respectively. RESULTS Compared with the model group, the value of FBG and TG, TC, LDL-C of berberine group were decreased, while HDL-C were increased. Berberine could suppress alterations in pathological changes of the kidney, downregulate the expression of TGF-β1 and IL-18 in the kidney of diabetic rats with nephropathy. CONCLUSION Berberine could significantly ameliorate the renal injury of the model rats by suppressing the expression of TGF-β1 and IL-18 in the kidney.