摘要
目的探讨右美托咪定对脓毒症大鼠肾损伤的影响,并分析其与长链非编码RNA(lncRNA)-HOX转录反义RNA(HOTAIR)信号通路的相关性。方法用脂多糖(LPS)静脉注射建立脓毒症大鼠模型。空白组(n=20)予以0.9%氯化钠注射液;对照组(n=20)予以右美托咪定;模型组(n=20)LPS静脉注射后予以生理盐水;实验组(n=20)先予以LPS静脉注射后予以右美托咪定持续静脉泵注,给药6 h。用实时荧光定量PCR检测肾组织LncRNA-HOTAIR水平,用蛋白质印迹法检测大鼠肾组织的核因子κB(NF-κB)p65、自噬相关分子微管相关蛋白轻链3Ⅱ(LC3Ⅱ)、B淋巴细胞瘤-1(Bcl-1)及蛋白激酶(PINK1)蛋白表达水平,用试剂盒检测肿瘤坏死因子-α(TNF-α)水平。结果实验组、模型组、对照组、空白组大鼠肾组织中的HOTAIR水平为分别为1.79±0.25,2.14±0.31,0.63±0.14,0.65±0.17;NF-κB p65水平为分别为0.91±0.02,1.23±0.02,0.41±0.03,0.43±0.03;LC3Ⅱ水平分别为2.27±0.61,2.72±0.74,0.63±0.11,0.65±0.12;Bcl-1水平分别为2.31±0.67,2.79±0.81,0.71±0.19,0.71±0.15;PINKI水平分别为2.01±0.49,2.41±0.65,0.57±0.09,0.59±0.11;TNF-α水平为分别为(2.83±0.38),(3.27±0.51),(1.90±0.36),(1.92±0.25)ng·mL^-1。实验组分别与模型组、对照组、空白组比较,模型组与对照组、空白组比较上述指标的差异均有统计学意义(均P<0.05);大鼠肾组织HOTAIR与NF-κB p65及TNF-α呈明显正相关(ρ=0.790,0.745;P<0.05),且NF-κB p65与TNF-α亦呈明显正相关(ρ=0.784;P<0.05)。结论右美托咪定可通过下调LncRNA-HOTAIR信号通路,减少NF-κB p65产生,使TNF-α表达降低,缓解炎症反应,减轻肾损伤。
Objective To investigate the effect of dexmedetomidine on renal injury in rats with sepsis,and to analyze the correlation between dexmedetomidine and long non coding RNA(LncRNA)-Hox transcription antisense RNA(HOTAIR)signal pathway.Methods The sepsis rat model was established by intravenous injection of lipopolysaccharide(LPS),blank group(n=20)was given normal saline injection;control group(n=20)was given dexmedetomidine;model group(n=20)was given LPS intravenous injection and then normal saline;test group was given the LPS injection,then given dexmedetomidine continuously,the drug was administered for 6 hours.Using the real-time fluorescent quantitative PCR to detected the level of LncRNA-HOTAIR in renal tissue,and using the Western blot to detect the expression of nuclear factor-κB(NF-κB)p65,microtubule associated protein light chain 3Ⅱ(LC3Ⅱ),B-lymphoma-1(Bcl-1)and phosphatase and tensin homologue(PTEN)-induced putative kinase 1(PINK1)in kidney tissue of rats.Results The levels of HOTAIR in renal tissue of test group,model group,control group and blank group were 1.79±0.25,2.14±0.31,0.63±0.14,0.65±0.17;the levels of NF-κB(p65)were 0.91±0.02,1.23±0.02,0.41±0.03,0.43±0.03;the levels of LC3Ⅱ were 2.27±0.61,2.72±0.74,0.63±0.11,0.65±0.12;the levels of Bcl-1 were 2.31±0.67,2.79±0.81,0.71±0.19,0.71±0.15;the levels of PINKI were 2.01±0.49,2.41±0.65,0.57±0.09,0.59±0.11;the tumor necrosis factor-α(TNF-α)were(2.83±0.38),(3.27±0.51),(1.90±0.36),(1.92±0.25)ng·mL^-1.There were statistically significant differences between the test group and the model group/the control group/the blank group,between the model group and the control group/the blank group(all P<0.05);HOTAIR was positively correlated with NF-κB(p65)and TNF-α(ρ=0.790,0.745;P<0.05),and NF-κB p65 was positively correlated with TNF-α(ρ=0.784;P<0.05).Conclusion Dexmedetomidine can reduce the production of NF-κB p65 by down regulating the lncRNA-hotair signal pathway,decrease the expression of TNF-α,alleviate the inflammatory response and renal injury.
作者
徐巍
杜晓燕
陈志冬
刘凤琪
何晓炜
朱冰楠
杨卿
XU Wei;DU Xiao-yan;CHEN Zhi-dong;LIU Feng-qi;HE Xiao-wei;ZHU Bing-nan;YANG Qing(Intensive Care Unit,the First Affiliated Hospital of Huzhou Normal University,Huzhou 313000,Zhejiang Province,China;Department of Respiratory,the First Affiliated Hospital of Huzhou Normal University,Huzhou 313000,Zhejiang Province,China;Department of Pharmacy,the First Affiliated Hospital of Huzhou Normal University,Huzhou 313000,Zhejiang Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2020年第20期3246-3249,共4页
The Chinese Journal of Clinical Pharmacology
基金
湖州市科技局2018年第二批科技计划基金资助项目(2018GY25)。
