摘要
目的:探究右美托咪定(dexmedetomidine,DEX)对糖尿病肾病(diabetic nephropathy,DN)大鼠肾损伤的作用及其机制。方法:将50只大鼠随机分为对照组(Control,Ctrl)组、链尿佐菌素(Streptozotocin,STZ)组、罗格列酮(rosiglitazone,Rosi)组、DEX 25μg/kg组和DEX 50μg/kg组。除Ctrl组外,其余组大鼠腹腔注射STZ,造模成功后DEX(25,50μg/kg)组大鼠腹腔注射DEX,Rosi组给予10 mg/kg的Rosi,7 d后进行检测。采用HE染色检测肾损伤,TUNEL检测细胞凋亡,试剂盒检测血清肌酸酐(serum creatinine,SCr)、血尿素氮(blood urea nitrogen,BUN)、尿白蛋白及超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)和丙二醛(malondialdehyde,MDA)的浓度,Western印迹检测Ki-67,cleaved Caspase-3,转化生长因子-β1(transforming growth factor-β1,TGF-β1),磷酸化-Smad2(phosphorylated-Smad2,p-Smad2)和p-Smad3的表达。结果:DEX和Rosi能显著减轻模型大鼠肾损伤,降低SCr,BUN和SOD的浓度,并以高浓度作用显著;DEX和Rosi还能显著减少肾组织细胞凋亡及cleaved Caspase-3的表达水平、诱导Ki-67的表达;同时,DEX及Rosi能升高模型大鼠血清SOD和GSH-Px的浓度,降低MDA的浓度;此外,DEX及Rosi能抑制TGF-β1,p-Smad2和p-Smad3表达,并有量效关系。结论:DEX能通过抑制TGF-β1/Smad信号通路的激活减轻DN大鼠的肾损伤。
Objective: To investigate the effects and mechanism of dexmedetomidine(DEX) on renal injury of diabetic nephropathy rats. Methods: A total of 50 rats were divided into Control group(Ctrl) group, Streptozotocin(STZ) group, rosiglitazone(Rosi) group, dexmedetomidine(DEX, 25 μg/kg) group and DEX(50 μg/kg) group. Rats were injected with STZ intraperitoneally except rats in the Ctrl group. After model was established successfully, rats in DEX(25, 50 μg/kg) groups were injected with DEX intraperitoneally, and rats in the Rosi group were treated with Rosi(10 mg/kg) for 7 d. The renal injury was determined by HE staining, TUNEL assay was performed for cell apoptosis, the concentrations of serum creatinine(SCr), blood urea nitrogen(BUN), urea protein, superoxide dismutase(SOD), glutathione peroxidase(GSH-Px) and malondialdehyde(MDA) also were measured. The protein levels of Ki-67, cleaved Caspase-3, transforming growth factor-β1(TGF-β1), phosphorylated-Smad2(p-Smad2) and p-Smad3 were determined by Western blot. Results: In model rats, the renal injury was alleviated by DEX and Rosi, and the concentration of SCr, BUN and SOD also were down-regulated by DEX and Rosi, especially high-dose. DEX and Rosi ameliorated cell apoptosis and the expression of cleaved Caspase-3, induced the expression of Ki-67. Meanwhile, DEX and Rosi up-regulated the concentrations of SOD and GSH-Px, but decreased the concentration of MDA. In addition, pretreatment of DEX inhibited the expression of TGF-β1, p-Smad2 and p-Smad3 in a dose-dependent manner. Conclusion: DEX can attenuates renal injury of DN rats through TGF-β1/Smad signaling pathway.
作者
杨燕
涂立刚
彭志宏
YANG Yan;TU Ligang;PENG Zhihong(Department of Anesthesiology,Xinyang Central Hospital,Xinyang Henan 464000,China)
出处
《临床与病理杂志》
2018年第11期2283-2291,共9页
Journal of Clinical and Pathological Research
基金
河南省科技攻关项目(142102310246)~~
