右美托咪啶对异氟醚致新生鼠海马神经细胞凋亡的影响

【摘要】 目的 比较右美托咪啶(Dex)预处理给药和分次给药两种方法对异氟醚(Iso)致新生大鼠海马细胞凋亡的影响。方法 将出生后7天(postnatal day 7, P7)的SD大鼠随机分成6组:空气+盐水组(Air+NS组)、空气+Dex 25 μg·kg-1分次给药组(Air+Dex25×3组)、空气+Dex 75 μg·kg-1预处理组(Air+Dex75组)、异氟醚+盐水组(Iso+NS组)、异氟醚+ Dex 25μg·kg-1分次给药组(Iso+Dex25×3组)以及异氟醚+Dex 75μg·kg-1预处理组(Iso+Dex75组)。前3组吸入空气,后3组吸入0.75%异氟醚6 h。Air+NS组、Iso+NS组、Air+Dex75组和Iso+Dex75组在麻醉前20 min腹腔内注射生理盐水或75 μg·kg-1剂量的Dex;Air+Dex25×3组和Iso+Dex25×3组分别在麻醉前20 min,麻醉开始后2 h和4 h腹腔内重复注射25μg·kg-1剂量的Dex。麻醉结束后用原位末端标记(TUNEL)法检测海马神经细胞凋亡(n=4); 用Western blot检测海马激活型caspase-3蛋白表达变化(n=4)。 结果 异氟醚能诱导海马CA1区TUNEL阳性细胞数增加391.0 %(P<0.001);激活型caspase-3表达增加122.0%(P<0.001)。Iso +Dex25×3组和Iso+Dex75分别减少异氟醚诱导的TUNEL阳性细胞的增加为80.7%(P<0.001)和73.2%(P<0.001);两组均能完全抑制激活型caspase-3表达的增加(P<0.001);两组间无统计学差异(P>0.05)。结论 右美托咪啶预处理给药和分次给药都能通过抑制海马细胞凋亡来减轻异氟醚对新生大鼠的脑毒性作用,且两者的抗凋亡效果相似。

Effects of dexmedetomidine on isoflurane-induced apoptosis of hippocampal nerve cells in neonatal Rats

Objective To compare the effects of pretreatment or repeated treatment with dexmedetomidine on isofiurane-indueed neuroapoptosis in the hippoeampi of neonatal rats. Methods 48 postnatal day 7 （PT） Sprague-Dawley rats were randomly assigned into air ＋ saline （Air＋NS） group, air＋dexmedetomidine 25 μg/kg for three times （Air＋Dex25×3） group, air ＋ dexmedetomidine 75 μg/ kg （Air＋Dex75） group, isoflurane＋saline （Iso＋NS） group, isoflurane ＋ dexmedetomidine 25 p.g/kg for three times （Iso＋Dex25×3） group and isoflurane ＋ dexmedetomidine 75 μg/kg （Iso＋Dex75） group. Rats were injected intraperitoneally with saline or dexmedetomidine at a dose of 75μg/kg 20 min before the exposure to 0.75% isoflurane or air for 6 h. Rats in the group Air＋Dex25×3 and group Iso＋Dex25 x3 were injected intraperitoneally with 25 μg/kg dexmedetomidine for three times （at 20rain before, 2 h and 4 h during gas exposure）. Some rats were used for TUNEL staining at 2 h after the termination of anesthesia （n =4）. The other rats were sacrificed immediately upon the termination of anesthesia and their hippocampi were used for Western blot of cleaved caspase-3 （n = 4）. Result Isoflurane increased the number of TUNEL positive cells in hippocampal CA1 area and the expression of cleaved caspase-3 protein by 391.0%（P〈0.001） and 122.0% （P〈0.O01）, respectively.Pretreatment and repeated treatment with dexmedetomidine not only inhibited the increase of isoflurane- induced TUNEL positive cells by 73.2% （P〈0.001） and 80.7% （P〈0.001）, but also reversed the increase of cleaved caspase-3 expression induced by isoflurane completely. Meanwhile, these treatments provided similar antiapoptosis effects. Conclusions Pretreatment and repeated treatment with dexmedetomidine provided similar neuroprotection against isoflurane-induced neuroapoptosis in the hippocampi of neonatal rats.