右美托咪定通过调控TGF-β1/Smad通路对糖尿病肾病大鼠肾损伤的保护作用
| 作者: |
1杨燕,
1涂立刚,
1彭志宏
1 信阳市中心医院麻醉科，河南 信阳 464000 |
| 通讯: |
杨燕
Email: yourongli_83@163.com |
| DOI: | 10.3978/j.issn.2095-6959.2018.11.001 |
| 基金: | 河南省科技攻关项目(142102310246)。 |
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 25 μg/kg组和DEX 50 μg/kg组。除Ctrl组外，其余组大鼠腹腔注射STZ，造模成功后DEX(25，50 μg/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。
关键词：
右美托咪定；糖尿病肾病；氧化应激；TGF-β1；Smad
Protective effect of dexmedetomidine on renal injury in diabetic nephropathy rats by regulating TGF-β1/Smad signaling pathway
CorrespondingAuthor: YANG Yan Email: yourongli_83@163.com
DOI: 10.3978/j.issn.2095-6959.2018.11.001
Foundation: This work was supported by Henan Science and Technology Tackling Key Project Foundation, China (142102310246).
Abstract
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.
Keywords：
dexmedetomidine; diabetic nephropathy; oxidative stress; TGF-β1; Smad