左归降糖益肾方对糖尿病肾病MKR鼠肾组织miRNA-181a及GRP78表达的影响  

Effects of Zuogui Jiangtang Yishen Decoction on the expressions of miRNA-181a and GRP78 of MKR mice with diabetic nephropathy

作　　者：陈聪[1,2] 陈家旭[2] 喻嵘[3] CHEN Cong;CHEN Jia-xu;YU Rong(Guiyang College of Traditional Chinese Medicine,Guiyang 550025,China;Beijing University of Chinese Medicine,Beijing 100029,China;Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]贵阳中医学院,贵阳550025 [2]北京中医药大学,北京100029 [3]湖南中医药大学,长沙410208

出　　处：《中华中医药杂志》2018年第10期4677-4680,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：贵州省科学技术基金项目(No.黔科合基础[2016]1012);贵州省中医药管理局中医药;民族医药科学技术研究课题(No.QZYY-2016-007);贵州省教育厅青年科技人才成长项目(No.黔教合KY字[2016]191号);国家自然科学基金地区科学基金项目(No.81860818)~~

摘　　要：目的:探讨左归降糖益肾方对糖尿病肾病(DN)骨骼肌特异性胰岛素样生长因子-1受体缺失转基因鼠(MKR鼠)肾组织miRNA-181a及GRP78表达的影响。方法:8周龄MKR鼠,按性别、空腹血糖、体质量随机分为空白组,模型组(高脂喂养联合单侧肾切除),左归降糖益肾方组,阳性药物组(格列喹酮片0.0039g/kg+盐酸贝那普利片0.0013g/kg),4-苯基丁酸组(1.44g/kg),每组15只;同龄C57鼠10只作为正常组。造模后8周灌胃给药,左归降糖益肾方28.8g/kg灌胃治疗8周。留取尿标本,心脏采血处死各组小鼠。电化学法检测空腹血糖,酶联免疫吸附法(ELISA)检测尿微量白蛋白含量;荧光PCR检测肾组织miRNA-181a表达水平,逆转录-聚合酶链反应法(RT-PCR)和Western blot法分别检测肾组织GRP78 mRNA及蛋白表达水平;电镜观察肾组织病理变化。结果:与模型组比较,左归降糖益肾方能降低DN小鼠空腹血糖及尿微量白蛋白含量(P﹤0.01),并能调控miRNA-181a及GRP78的表达水平(P﹤0.01);疗效等同于阳性药物组;并能改善肾组织病理损伤。结论:左归降糖益肾方可通过调控miRNA-181a、GRP78表达水平,从而抑制肾组织损伤。Objective： To observe the effects of the Zuogui Jiangtang Yishen Decoction （ZJYD） on the expressions of miRNA-181a and GRP78 of MKR mice with diabetic nephropathy. Methods： According to sex and fasting blood-glucose （FBG） and body weight, 8 weeks of MKR mice, which were dominant-negative insulin-like growth factor-1 receptor specifically targeted to the skeletal muscle, were randomly divided into 5 groups： control group, high-fat diet feed and mono-nepbrectomy model group, Z.IYD group, positive control group （Gliquidone 0.0039g/kg＋Benazepril hydrochloride 0.0013g/kg）, 4-PBA group （1.44g/ kg）. Fifteen mice in each group, ten C57 mice was as normal group. Eight weeks after operation, the mice were gavaged for eight weeks of ZJYD of 28.8g/kg for 8 weeks. Urine and heart blood were collected; the levels of FBG and UmAlb were observed by electrochemical method or ELISA respectively, the protein or mRNA expressions of GRF78 of kidney tissue were analyzed by Western blot or reverse transcription-polymerase chain reaction （RT-PCR） respectively; and the expressions of miRNA-181a was measured by fluorescent PCR; the effects of ZJYD on pathological changes in the renal tissues was assessed by transmission electron microscope. Results： Compared with model group, the ZJYD decreased the fasting blood-glucose （P〈0.01）, urinary microalbumin content （P〈0.01）, and regulated expressions of GRF78 and miRNA-181a （P〈0.01）. The curative effect is equivalent to that of the positive drug group, and improved the pathological damage of kidney tissue. Conclusion： ZJYD can inhibit the develonment of renal injury hv regulating the exnressions of GRP78 and miRNA-181a.

关 键 词：左归降糖益肾方 MKR鼠 糖尿病肾病 miRNA-181a GRP78 

分 类 号：R285.5[医药卫生—中药学]