摘要
目的探讨蛇床子素(OST)对糖尿病肾病(DN)模型小鼠肾间质纤维化的影响。方法采用一次性尾静脉注射链脲佐菌素建立糖尿病小鼠模型,成功后继续喂养12周建立DN模型。将糖尿病模型小鼠分为模型组和OST低、中、高剂量(20、40、80 mg/kg)组,每组10只,糖尿病造模成功后每日灌胃相应药物或溶剂(模型组)1次,持续12周;同时设置正常对照组。末次灌胃后,检测各组小鼠空腹血糖、24 h尿蛋白、血肌酐(Scr)、尿素氮水平;Masson染色法观察肾间质区域胶原纤维的沉积情况;免疫组化染色法检测肾皮质中E-钙黏蛋白(E-cadherin)和波形蛋白(vimentin)的表达;Western blot法检测肾皮质中卵泡抑素样蛋白1(Fstl1)、锌指转录因子1(Snail1)蛋白表达和蛋白激酶B(Akt)磷酸化水平(以p-Akt/Akt比值计)。结果与正常对照组比较,模型组小鼠空腹血糖、24 h尿蛋白、Scr、尿素氮水平,肾间质胶原纤维沉积占比,肾皮质中vimentin表达水平以及Fstl1、Snail1蛋白表达水平和p-Akt/Akt比值均显著升高(P<0.01),E-cadherin表达水平显著降低(P<0.01)。与模型组比较,OST各剂量组小鼠上述指标变化均显著逆转(P<0.05或P<0.01)。结论OST预防性用药可有效降低DN模型小鼠的空腹血糖,保护其肾功能,抑制肾小管上皮细胞间充质转分化,延缓肾间质纤维化进程,其作用机制可能与抑制Fstl1/Akt/Snail1通路有关。
OBJECTIVE To investigate the effects of osthole(OST)on renal interstitial fibrosis in diabetic nephropathy(DN)model mice.METHODS The diabetic mice model was established by the tail vein injection of streptozotocin once,and the DN model was established by feeding for 12 weeks after successful modeling of diabetes.Diabetic model mice were randomly divided into model group,low-dose,moderate-dose,high-dose groups(20,40,80 mg/kg)of OST,with 10 mice in each group.After successful modeling of diabetes,the mice were given corresponding drugs or solvent(model group)intragastrically,once a day,for consecutive 12 weeks,and the normal control group was set up at the same time.After the last administration,the levels of fasting blood glucose,24 h urinary protein,serum creatinine(Scr)and blood urea nitrogen were tested in each group.Masson staining was used to observe the deposition of collagen fibers in renal interstitium;the expressions of E-cadherin and vimentin in renal cortex were detected by immunohistochemical staining.The protein expressions of follistatin-like protein 1(Fstl1)and Snail family transcriptional repressor 1(Snail1),the phosphorylation of protein kinase B(Akt)(calculated by p-Akt/Akt)in the renal cortex were detected by Western blot.RESULTS Compared with normal control group,the levels of fasting blood glucose,24 h urinary protein,Scr and blood urea nitrogen,collagen fiber deposition ratio of renal interstitium,the expression of vimentin,protein expressions of Fstl1 and Snail1,p-Akt/Akt in renal cortex were increased significantly(P<0.01),as well as the expression of E-cadherin was decreased significantly(P<0.01).Compared with model group,above indexes of OST groups were reversed significantly(P<0.05 or P<0.01).CONCLUSIONS Preventive use of OST can effectively reduce fasting blood glucose level,protect renal function and inhibit epithelial-mesenchymal transition of DN model mice,and delay the progression of renal interstitial fibrosis,the mechanism of which may be associated with the suppression of Fstl1/Akt/Snail1 signaling pathway.
作者
黄倩
郑丹丹
黄秋虹
施子禄
HUANG Qian;ZHENG Dandan;HUANG Qiuhong;SHI Zilu(Teaching and Research Section of Physiology,Basic Medicine Department,Quanzhou Medical College,Fujian Quanzhou 362100,China;Dept.of Nephrology,Quanzhou First Hospital Affiliated to Fujian Medical University,Fujian Quanzhou 362000,China)
出处
《中国药房》
CAS
北大核心
2022年第22期2719-2723,共5页
China Pharmacy
基金
国家自然科学基金资助项目(No.31471100)
福建省中青年教师教育科研项目(科技类)(No.JAT201237)
泉州市科技计划项目(No.2018Z179)。
关键词
蛇床子素
糖尿病肾病
间质纤维化
卵泡抑素样蛋白1
蛋白激酶B
锌指转录因子1
小鼠
osthole
diabetic nephropathy
interstitial fibrosis
follistatin-like protein 1
protein kinase B
Snail family transcriptional repressor 1
mice
