知柏药对原料提取物对小鼠糖尿病周围神经病变的药效作用

【目的】探讨知柏药对原料的提取物对小鼠糖尿病周围神经病变的药效学作用。【方法】采用腹腔注射链脲佐菌素(STZ,剂量为30 mg/kg)联合喂食高脂饲料诱导小鼠糖尿病模型,将160只雄性C57BL/6j小鼠随机分为8组,每组20只,分别为正常组,模型组,二甲双胍组(剂量为130 mg/kg),血脂康组(剂量为200 mg/kg),知母提取物高、低剂量组(剂量分别为360、90 mg/kg),黄柏提取物高、低剂量组(剂量分别为135、45 mg/kg),给药24周。分别在给药8周、16周、24周时,测定血浆葡萄糖(GLU)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、胰岛素(INS)水平;给药10周时,进行葡萄糖糖耐量试验(OGTT);给药24周时检测血浆核因子-κB(NF-κB)活性和转化生长因子β1(TGF-β1)、超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)水平。【结果】注射STZ 5周后,与正常组比较,模型组体质量先升高后明显下降,而空腹血糖显著升高(P0.05)。与正常组比较,模型组小鼠FBG、TC、TG、LDL-C、INS水平均显著性升高(P0.01或P0.001);血浆NF-κB活性、TGF-β1及SOD水平显著升高,GSH水平显著下降,差异均有统计学意义(P0.01或P0.001);与模型组比较,知母提取物高、低剂量组,黄柏提取物高、低剂量组小鼠的FBG、TC、TG、LDL-C、INS水平均有不同程度降低;经连续给药后,知母提取物高剂量组、黄柏提取物高剂量组小鼠血浆中NF-κB活性,TGF-β1及SOD水平均显著降低(P0.05或P0.001),血浆GSH水平显著升高(P0.01)。【结论】知柏药对原料的提取物降糖效果明显,对糖尿病模型小鼠的糖尿病周围神经病变具有明显的保护作用。

Pharmacodynamics Study of Extract from Raw Material of Rhizoma Anemarrhenae and Cortex Phellodendri for Treatment of Mice with Diabetic Peripheral Neuropathy

Objective To explore the pharmacodynamic action of the extract from raw materials of Rhizoma Anemarrhenae and Cortex Phellode ndri, a classic herb pair in traditional Chinese medicine, on mice with diabetic peripheral neuropathy(DNP). Methods The mice were administrated with intraperitoneal injection of streptozotocin (STZ, 30 mg/kg) and fed with high-fat diet to establish the DNP mouse model. One hundred and sixty male C57BL/6j mice were divided into normal group, model group, metfomin group(130 mg/kg), Xuezhikang group(200 mg/kg), high- and low-dose Rhizoma Anemarrhenae extract group(360, 90 mg/kg) , high-and low-dose Cortex Phellodendri extract group(135, 45 mg/kg), 20 mice in each group. The medication lasted for 24 weeks. On medication week 8, 16 and 24, the plasma levels of glucose (GLU), total cholesterol (TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C) and insulin(INS) were determined respectively. On medication week 10, oral glucose tolerance test(OGTT)was carried out. On medication week 24, the plasma nuclear factor kappa B(NF-κB) activity and the plasma levels of transforming growth factor-beta 1(TGF-β1), superoxide dismutase(SOD) and reduced glutathione(GSH) were detected. Results Five weeks after injection of STZ, the body mass of the model group was firstly increased and then decreased, and FBG was increased(P<0.05 compared with the normal group). Compared with the normal group, FBG, TC, TG, LDL-C and INS levels were increased(P<0.01 or P<0.001), plasma NF-κB activity, TGF-β1 and SOD levels were enhanced, and GSH level was decreased in the model group, the difference being statistically significant (P<0.01 or P<0.001). Contrasted with the model group, FBG, TC, TG, LDL-C and INS levels in high-and low-dose Rhizoma Anemarrhenae extract group and in high-and low-dose Cortex Phellodendri extract group were decreased to various degrees. After continuous medication, plasma NF-κB activity and TGF-β1 and SOD levels in high-dose Rhizoma Anemarrhenae extract group and in high-dose Cortex Phellodendri extract group were reduced(P<0.05 or P<0.001), and plasma GSH level was increased(P<0.01). Conclusion Extract from raw materials of Rhizoma Anemarrhenae and Cortex Phellodendri has obvious hypoglycemic effect and protective effect on experimental mice with DPN.