右美托咪定调节RhoA/ROCK信号通路对子宫平滑肌收缩的影响  

Effect of dexmedetomidine on uterine smooth muscle contraction by regulating the RhoA/ROCK signaling pathway

作　　者：李彦 王毅 黄韫哲 陈明倩 LI Yan;WANG Yi;HUANG Yunzhe;CHEN Mingqian(Department of Anesthesiology,Affiliated Minda Hospital of Hubei Minzu University,Enshi,Hubei 445000,China;Department of Gynecology,Affiliated Minda Hospital of Hubei Minzu University,Enshi,Hubei 445000,China)

机构地区：[1]湖北民族大学附属民大医院麻醉科,湖北恩施445000 [2]湖北民族大学附属民大医院妇科,湖北恩施445000

出　　处：《中国优生与遗传杂志》2024年第10期2039-2044,共6页Chinese Journal of Birth Health & Heredity

摘　　要：目的探究右美托咪定(DEX)是否通过调节Ras同源基因家族蛋白A(RhoA)/Rho相关蛋白激酶(ROCK)信号通路进而影响子宫平滑肌收缩。方法取已孕临产雌性Wistar大鼠20只,每只子宫分离3段平滑肌组织,置于恒温水浴槽中,静息张力设定1.0 g,采用累积给药法观察终浓度为0、1×10^(-7)、1×10^(-6)、1×10^(-5)mol/L的DEX对子宫平滑肌自主收缩的频率和幅度的影响。原代分离大鼠子宫平滑肌细胞通过免疫荧光技术鉴定,激光共聚焦显微镜检测细胞中Ca^(2+)浓度;Western blot检测RhoA、ROCK2和肌球蛋白磷酸酶(MYPT1)磷酸化(p-MYPT1)蛋白以及DEX和RhoA激活剂干预各蛋白质的表达。结果DEX终浓度为1×10^(-6)和1×10^(-5)mol/L时离体大鼠子宫平滑肌收缩强度减弱,收缩频率与时间延长(P<0.05);DEX处理大鼠子宫平滑肌细胞显著降低Ca^(2+)浓度(P<0.05),DEX与水仙环素(narciclasine,Nac)联合处理大鼠子宫平滑肌细胞Ca^(2+)浓度增加(P<0.05)。DEX处理大鼠子宫平滑肌细胞,RhoA、ROCK2和p-MYPT1蛋白表达降低(P<0.05),RhoA激活剂水仙环素干预后,RhoA、ROCK2和p-MYPT1蛋白表达有所升高(P<0.05)。结论右美托咪定通过调节RhoA/ROCK信号通路,影响子宫平滑肌收缩。Objective To investigate whether dexmedetomidine(DEX)affects uterine smooth muscle contraction by regulating the Ras homolog gene family member A(RhoA)/Rho associated protein kinase(ROCK)signaling pathway.Methods Twenty pregnant female Wistar rats who were about to give birth were selected.Three segments of smooth muscle tissue were separated from each uterus and placed in a constant temperature water bath.The resting tension was set at 1.0 g.The cumulative administration method was used to observe the effects of DEX with final concentrations of 0,1×10^(‒7),1×10^(‒6),1×10^(‒5)mol/L on the frequency and amplitude of uterine smooth muscle spontaneous contraction.Primary isolated rat uterine smooth muscle cells were identified by immunofluorescence technology.Laser confocal microscopy was used to detect the concentration of Ca^(2+)in cells.Western blot was used to detect the expression of RhoA,ROCK2,and myosin phosphatase(MYPT1)phosphorylation(p-MYPT1)proteins,and various proteins intervened by DEX and RhoA activators.Results When the final concentration of DEX was 1×10^(‒6) and 1×10^(‒5) mol/L,the contraction intensity of uterine smooth muscle of isolated rat was weakened,and the contraction frequency and time were prolonged(P<0.05).DEX treatment greatly reduced the concentration of Ca^(2+)in rat uterine smooth muscle cells(P<0.05),while DEX combined with daffodil increased the concentration of Ca^(2+)in rat uterine smooth muscle cells(P<0.05).DEX treatment of rat uterine smooth muscle cells resulted in decreased expression of RhoA,ROCK2,and p-MYPT1 proteins(P<0.05).After intervention with RhoA activator narcissus,the expression of RhoA,ROCK2,and p-MYPT1 proteins increased(P<0.05).Conclusion Dexmedetomidine affects uterine smooth muscle contraction by regulating the RhoA/ROCK signaling pathway.

关 键 词：右美托咪定 Ras同源基因家族蛋白A/Rho相关蛋白激酶 子宫平滑肌 大鼠 

分 类 号：R614[医药卫生—麻醉学]