摘要
目的:观察并证实益气养阴、祛痰化瘀中药复方对早期糖尿病肾病大鼠干预作用,分析其可能的作用机制,为临床防治糖尿病肾病提供可靠的实验依据。方法:实验于2005-01/12在解放军沈阳军区总院动物实验中心完成。SPF级雄性Wistar大鼠72只,随机选出正常组12只,其余大鼠高糖高脂饲料喂养1个月后,腹腔注射链脲佐菌素建立早期糖尿病肾病大鼠模型。造模成功大鼠56只以随机排列表分为4组:模型组、中药10,20g/kg组及中药预防组各14只。中药预防组在成模后立即开始给药,中药10,20g/kg组在成模后2周开始给药。预防组与10g/kg组给予10.15g/(kg·d),20g/kg组给予20.30g/(kg·d)灌胃;正常对照组及模型组灌服相应容量(10mL/kg)的生理盐水,1次/d,连续6周。采用生化法、放射免疫法和蛋白质印迹杂交法等分析血糖、尿微量白蛋白、α1微球蛋白、血清肌肝、尿素氮水平,观察肾皮质转化生长因子β1、血小板衍化生长因子B蛋白表达。结果:纳入实验观察的大鼠共72只,造模不成功4只,模型组死亡3只,中药预防组死亡2只,中药10g/kg组死亡3只,中药20g/kg组死亡2只,最终纳入结果分析58只。①治疗后6周,模型组、中药10,20g/kg组、中药预防组血糖均明显高于正常组(P<0.01);各中药组血糖均低于模型组(P<0.05～0.01);中药预防组血糖低于10,20g/kg组(P<0.01,0.05)。②治疗后6周,模型组、中药10,20g/kg组、中药预防组尿微量白蛋白、尿α1微球蛋白均高于正常组(P均<0.01);各中药组两指标均低于模型组(P均<0.01),中药10g/kg组高于预防组(P<0.01,0.05)。③治疗后6周,模型组、中药10,20g/kg组、中药预防组血尿素氮、血清肌肝均高于正常组(P均<0.01);中药10,20g/kg组、预防组两指标均低于模型组(P<0.05～0.01),10g/kg组高于预防组(P<0.01)。④早期糖尿病肾病大鼠肾皮质转化生长因子β1和血小板衍化生长因子B蛋白表达增加,中药预防组、20g/kg组对两者的表达均有明显抑制作用,各治疗组与模型组间均有显著差别。结论:益气养阴、祛痰化瘀中药复方能有效防治糖尿病肾病,其药效学机制可能通过降低血糖,减少尿微量白蛋白、α1-微球蛋白的水平,改善肾功能,下调肾皮质转化生长因子β1、血小板衍化生长因子B蛋白的过度表达实现。
dAIM： To observe and verify the intervention action and its mechanism of Chinese herb recipe of supplementing qi and nourishing y/n plus eliminating phlegm and resolving stasis in rats with early diabetic nephropathy, so as to provide experimental evidence for the clinic prevention of diabetic nephropathy.METHODS： The experiment was carried out in animal experiment center of General Hospital of Shenyang Military Area Command from January to December 2005. Twelve of 72 SPF grade Wistar rats were randomly selected as control group, and the rest animals were feed with high sucrose and fat diet for one month to establish the models of early diabetic nephropathy by intraperitoneal injection of streptozocin. The successfully modeling rats were randomly divided into model group, Chinese herb 10 g/kg and 20 g/kg groups and preventive group with 14 animals in each group. The rats of the last group were immediately treated with Chinese herb. The 10 and 20 g/kg herb groups were given administration since the second week after modeling. The preventive group and 10 g/kg herb group were given 10.15 g/kg daily, and the 20 g/kg group was given 20.30 g/kg daily; the normal group and model group were fused with 10 mL/kg normal saline, once daily for six weeks. The blood glucose, urine albumin and α 1-microglobulin, serum creatinine, urea nitrogen and the expressions of renal cortical transforming growth factor β 1 （TGF-β1） protein and platelet-derived growth factor B （PDGF-B） protein were measured with biochemistry, radioimmunoassay and Western blot methods.RESULTS： Among the 72 rats, 4 were not modeled successfully, 3 in the model group, 2 in the preventive group, 3 in the 10 g/kg group and 2 in the 20 g/kg group were died. Finally, 58 rats were involved in the result analysis. ①Six weeks after treatment, the blood glucose of the model group, 10 g/kg group, 20 g/kg group and preventive group were significantly higher than the normal group （P〈 0.01）; the blood glucose of each herb group was lower than the model group （P 〈 0.05-0.01）; that of the preventive group was lower than two herb groups （P 〈 0.01, 0.05）.②Six weeks after treatment, the urine albumin and αl-microglobulin of the model group, 10 g/kg group, 20 g/kg group and preventive group were significantly higher than the normal group （P 〈 0.01）; those of the herb groups were lower than the model group （P〈 0.01）, and the 10 g/kg group was higher than the preventive group （P〈 0.01, 0.05）. ③Blood urea nitrogen and serum creatinine of the model group, 10 and 20 g/kg herb groups and preventive group were significantly higher than the normal group after 6 weeks treatment （P 〈 0.01 ）. those of the herb groups and preventive group were lower than the model group （P 〈 0.05-0.01）, and the 10 g/kg group was higher than the preventive group （P 〈 0.01）. ④The expressions of TGF-β1 and PDGF-B protein in renal cortex were increased in the rats with early diabetic nephropathy. The Chinese herb and preventive groups could inhibit these expressions, and there were significant differences between the treatment groups and model group. CONCLUSION： Chinese herb compound of supplementing qi and nourishing yin and eliminating phlegm and resolving stasis could prevent and treat diabetic nephropathy effectively. Its pharmacodynamic mechanism may be associated with the regulation of glycometabolism, reduce of urine albumin and α 1-microglobulin, improvement of kidney function, and down-regulation of the hyper-expressions of TGF-β1 and PDGF-B protein in renal cortex.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2007年第29期5745-5748,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
