芪卫颗粒对自发性2型糖尿病KK-Ay小鼠肾功能的影响及机制  

Effect and the mechanism of Qiwei Granules on renal function in KK-Ay mice with spontaneous type 2 diabetes

作　　者：田年秀 王晓磊[2] 高彦彬[2] TIAN Nian-xiu;WANG Xiao-lei;GAO Yan-bin(National Center for Geriatric Diseases, Beijing Hospital, Beijing 100730, China;School of Traditional Chinese Medicine,Beijing Key Lab of TCM Collateral Research, Capital Medical University, Beijing 100069)

机构地区：[1]北京医院国家老年医学中心,北京100730 [2]首都医科大学中医药学院中医药络病研究北京市重点实验室,北京100069

出　　处：《北京中医药》2019年第1期21-25,F0003,共6页Beijing Journal of Traditional Chinese Medicine

基　　金：北京市自然科学基金项目-北京市教育委员会科技计划重点项目(KZ201610025024);国家重点基础研究发展计划(973计划)项目(2012CB518602)

摘　　要：目的观察芪卫颗粒对自发性2型糖尿病KK-Ay小鼠肾功能的影响及机制。方法 8周龄雄性KK-Ay小鼠高脂饲料喂养至12周制备糖尿病肾病模型,将造模成功的KK-Ay小鼠随机分为模型组、西药缬沙坦组、芪卫颗粒组,PERK抑制剂GSK2656157组各8只,并以C57BL/6J小鼠8只作为正常对照组。各组小鼠每日予相应药物灌胃。动态监测小鼠空腹血糖(FBG)、24 h尿微量白蛋白排泄率(UAER)。连续给药8周后,麻醉处死取血尿及肾组织,测定血尿素氮(BUN)及肌酐(SCr)含量,并取肾皮质行HE染色观察病理变化;Western blotting法检测肾组织内质网应激相关蛋白GRP78、PERK及P-PERK的表达。结果与模型组比较,芪卫颗粒组能明显减轻小鼠蛋白尿及改善肾功能(P<0.05),肾组织GRP78和P-PERK的蛋白表达明显下降(P<0.05),肾组织病理变化改善显著。结论芪卫颗粒可减少自发性2型糖尿病KK-Ay小鼠尿蛋白,改善其肾功能,其作用机制可能与抑制内质网应激PERK通路相关。Objective To study the effects and the mechanism of Qiwei Granules on the expression of renal function in KK-Ay mice with spontaneous type 2 diabetes. Methods 8-week-old male KK-Ay mice were fed by research forage for 12 weeks to establish model with diabetic nephropathy,the model mice were randomly divided into model group,Valsartan group,Qi-wei Granules group,PERK inhibitor group with 8 mice in each group. 8 C57BL/6J mice were set up as the control group. All the mice received daily gavage administration with corresponding medicines. Fasting plasma glucose(FBG),24 h urinary excretion(UAER)were examined. At age of 20 weeks,bloody urine and kidney tissue were obtained after anaesthetic death to examine the renal function(BUN,SCr). The pathological morphology of renal tissue were observed by hemmatoxylin eosin(HE)stain,while the protein expressions of GRP78 and PERK were measured by western blot. Results Compared with the model group,albuminuria and renal function were alleviated in Qiwei Granules group(P<0.05),the protein level of GRP78 and PERK were significantly decreased(P<0.05). The pathological changes of kidney tissue were obviously improved. Conclusion QWG could reduce albuminuria and improve renal function in KK-Ay mice with spontaneous type 2 diabetes. The protective effect may be associated with inhibition of PERK signaling pathways.

关 键 词：芪卫颗粒 糖尿病肾病 内质网应激 小鼠 

分 类 号：R285.5[医药卫生—中药学]