摘要
目的:观察槲皮素对糖尿病大鼠肾组织中磷酸化丝裂原活化蛋白激酶p38(p-p38MAPK)、核因子-κB P65(NF-κB P65)表达的影响。方法:采用一次性腹腔注射链脲佐菌素建立糖尿病大鼠模型,随机分为正常对照组、糖尿病模型组、阳性对照组(骁悉11 mg/kg)、槲皮素25 mg/kg、槲皮素50mg/kg,8周后测定各组大鼠血尿素氮(BUN)、血肌酐(Scr)、24h尿蛋白并处死取双肾,计算各组大鼠肾脏肥大指数。光镜下观察肾小球病理形态学变化,免疫组织化学法测定肾组织p-p38MAPK的含量,Western blot测定肾组织NF-κB P65的含量。采用酶联免疫吸附(ELISA)法测定血清白细胞介素8(IL-8)、转化生长因子-β(TGF-β)、纤维连接蛋白(FN)、纤溶酶原激活物抑制剂-1(PAI-1)。结果:与正常对照组比较,糖尿病模型组大鼠血清BUN、Scr含量,24 h尿蛋白,肾脏肥大指数均显著升高,糖尿病模型组血清IL-8、TGF-β、FN、PAI-1水平、肾组织p-p38MAPK及NF-κBP65表达显著升高。与模型组比较,槲皮素25、50mg/kg组大鼠血清BUN、Scr含量,24 h尿蛋白、肾脏肥大指数均显著降低,槲皮素25、50mg/kg组血清IL-8、TGF-β、FN、PAI-1水平、肾组织p-p38MAPK及NF-κBP65表达量显著降低,且明显改善肾小球病理变化。结论:槲皮素对糖尿病大鼠的肾脏保护作用可能通过调控肾脏p38MAPK/NF-κB信号通路,减轻炎症有关。
Objective： To study the influence of quercetin on kidney p38 mitogen-activated protein kinase / nuclear factor κB P65（ p38 MAPK / NF-κB） signaling pathway in diabetic rats. Methods： The diabetic rats were induced by a single intraperitoneal injection of streptozotocin. The rats were randomly divided into： normal group,diabetic model group,positive drug control group and Quercetin treatment group. The blood urea nitrogen（ BUN）,serum creatinine（ Scr） and 24 h urine protein of each group were measured. Both kidneys were taken out after the rats were killed,and the hypertrophy index of the rats in each group was calculated. Glomerular pathological morphology is observed under the light microscope,the content of p-p38 MAPK was determined by Immune histochemical method and the content of renal NF-κB P65 was determined by Western blot. The serum interleukin 8（ IL-8）,transforming growth factor-β（ TGF-β）,fibronectin（ FN） and fibrinolytic enzyme activators inhibitor 1（ PAI-1） were detected with the ELISA method. Results： Compared with the normal group,The BUN,Scr,and 24 h urine protein and hypertrophy index in the rat＇s kidney in the diabetic model were obviously enhanced,and the difference is statistically significant（ P 0. 05 or P 0. 01）. The IL-8,TGF-β,FN,PAI-1,p-p38 MAPK and NF-κB P65 protein of the kidney in the diabetic model were obviously enhanced,so the difference is also statistically significant（ P 0. 05 or P 0. 01）. Compared with the model group,the BUN,Scr and 24 h urine protein,and kidney＇s Hypertrophy Index of the kidney of the rat with Quercetin were significantly reduced,and the difference is statistically significant（ P 0. 05 or P 0. 01）. The IL-8,TGF-β,FN,PAI-1 in the kidney,p-p38 MAPK,NF-κB P65 protein of Quercetin were significantly reduced,so the difference is also statistically significant（ P 0. 05 or P 0. 01）,and the glomerular pathological morphology was significantly improved. Conclusion： The Quercetin can protect diabetic rat＇s kidney possibly by regulation p38 MAPK / NF-κB signaling pathway to anti-inflammatory mechanism.
出处
《中药药理与临床》
CAS
CSCD
北大核心
2016年第1期79-82,共4页
Pharmacology and Clinics of Chinese Materia Medica
基金
河南省教育厅高等学校重点科研项目(项目编号:15B180011)
