摘要
目的研究红景天苷(Salidroside,Sal)对糖尿病肾病(Diabetic nephropathy,DN)的保护作用及其作用机制。方法通过测定血浆脂质、β2-微球蛋白、血浆肌酐、血液尿素氮水平以及肾脏组织HE染色检测Sal对小鼠肾脏的保护作用。MTT法检测高级糖基终产物(Advaned glycation end product,AGE)对HK-2细胞活性的影响。免疫蛋白印记法检测Sal对AGE诱导的HK-2细胞中凋亡相关蛋白Bax、Bcl-2、细胞核因子2相关因子2(Nrf2)、TGF-β1以及胶原蛋白Ⅰ的蛋白表达,caspase-3和caspase-9试剂盒检测其活性。结果Sal能够降低DN模型体内血浆脂质、β2-微球蛋白、血浆肌酐和血液尿素氮水平。Sal能够减轻糖尿病对肾脏组织的损伤。Sal能够逆转由AGE诱导的HK-2细胞活性降低。Sal能够上调由AGE导致的Nrf2蛋白表达下调;TGF-β1以及胶原蛋白Ⅰ表达上调,Bax以及Bcl-2比例下降,caspase-3、caspase-9活性降低。结论Sal通过调控Nrf2的表达逆转由AGE引起的HK-2细胞凋亡以及糖尿病导致的肾脏组织损伤,进而对抗DN,产生类似二甲双胍(Metformin,MET)的作用。Sal可成为DN的潜在治疗药物。
Objective To investigate the protective effect and mechanism of Salidroside(Sa1)on diabetic nephropathy(DN).Methods The protective effects of Sal on the kidney of mice were detected by measuring the levels of plasma lipid,β2-microglobulin,creatine and blood urea nitrogen and by renal H E staining.The effects of AGE on cell viability of HK-2 cells were detected by MTT.The expression of proteins Bax,Bcl-2,Nrf2,TGF-β1 and collagen I in AGE-induced HK-2 cells were detected by Western blot.Activity of caspase-3 and caspase-9 was detected by ELISA kits.Results Sal could reduce the levels of plasma lipid,β2-microglobulin,creatine and blood urea nitrogen in DN model.Sal could reduce the damage to kidney cell induced by diabetes.Sal could reverse the reduced cell activity of HK-2 induced by AGE.Sal up-regulated the downregulation of Nrf2 protein expression caused by AGE;TGF-β1 and collagenⅠexpression was up-regulated,the ratio of Bax and Bcl-2 was decreased and the activity of caspase-3,-9 was decreased.Conclusion Sal can reverse the HK-2 cell apoptosis induced by AGE in DN and the damage to kidney caused by diabetes by regulating the expression of Nrf-2,which fights against DN and functions like Metformin.Sal can be a potential therapeutic drug for DN.
作者
殷白丁
胡玉霞
靳红
吐达洪
汪晶
YIN Bai-ding;HU Yu-xia;JIN Hong;TU Da-hong;WANG Jing(Beijing Shijitan Hospital,Beijing 100089,China;The Second Affiliated Hospital of Mudanjiang Medical College,Mudanjiang 157011,China)
出处
《实用药物与临床》
CAS
2020年第9期787-792,共6页
Practical Pharmacy and Clinical Remedies