摘要
目的研究亚麻醉深度（0．3MAC）的异氟醚和七氟醚对新生大鼠海马齿状回神经细胞增殖以及ERKl／2蛋白磷酸化表达的不同影响。方法72只P7新生鼠按照随机数字表随机分对照组（Con）、异氟醚组（Iso）和七氟醚组（Sev），各组分别吸入空气、0．75％异氟醚或1．2％七氟醚6h。各组动物分别在处理后即刻（DO）（n=6）和处理后3d（D3）（n=6）腹腔注射BrdUl00mg／kg，24h后用免疫组织化学法检测BrdU阳性细胞的数目。另外一些动物在D0天取新鲜海马组织，Westernblot检测激活型Caspase-3和磷酸化ERKl／2蛋白表达的变化（／7,：6）。剩下的动物用来检测血气和血糖的变化（n=6）。组间资料的比较采用单因素方差分析。结果在D0天，IsoD0组[（1332．43±192．70）个／mm2]，SevDO组[（1207．33±139．50）个／mm2]和ConDO组[（1362．40±227．90）个／mm2]3组BrdU阳性细胞数目差异无统计学意义；在D3天，IsoD3组[（604．56±65．77）爪／mm2]比ConD3组[（896．90±78．77）个／mm2]明显减少32．6％（P〈0．05）．而sevD3组『（808．73±41．27）个／mm2]与ConD3组比较差异无统计学意义。在Do天，Iso组Caspase-3表达比Con组增加195％（尸〈0．01），而Sev组只增加74％（尸〈0．05）。Iso组海马磷酸化ERKl／2P44和P42分别较Con组降低了53％（P〈0．01）和47％（P〈0．01）；Sev组磷酸化ERKl／2与Con组比较差异无统计学意义。结论亚麻醉深度异氟醚而非七氟醚通过抑制海马前体细咆增殖而干扰大鼠脑发育，降低海马磷酸化ERKl／2表达可能参与了异氟醚抑制神经细胞增殖的作用。
Objective To investigate the effects of isoflurane and sevoflurane at the equivalent depth of subanesthesia on neuronal proliferation and phosphorylation of extraceullar signal-regulated kinase 1/2 （ERK1/2） protein in the hippocampi of neonatal rats. Methods Seventy-two neonatal rats at postnatal day 7 were involved in this study and they were assigned randomly into isoflurane group （Iso group） ,sevoflurane group （Sev group） and control group （Con group）. The rats in I group, S group or C group were separately exposed to 0.75% isoflurane or 1.2% sevoflurane （ equivalent to 0.3 MAC for neonatal rats） or air for 6 h. Some rats in each group were injec- ted intraperitoneally BrdU 100 mg/kg immediately （DO） （ n = 6 ） or 3 days after exposure （D3） （ n = 6）, and their brains were perfusion and embedded by paraffin 24 h after BrdU injection. BrdU positive expressions in the in dentate gyrus （DG） area of hippocampus were detected by IHC staining. Besides, the fresh hippocampi of some rats each group were dissected at the end of anesthesia,caspase-3 and phospho-ERK1/2,ERK1/2 proteins expres- sion were detected by Western blot （ n = 6）. The other rats in each group were used to measure changes of pH and blood glucose （ n = 6）. One way ANOVA test was used for data analysis among groups. Results BrdU-positive cells had no significant difference among group IsoDO （（ 1332.43 ± 192.70）/mm2）, group SevDO （ 1207.33± 139.50 ）/mm2 ） , and group ConDO （ （ 1362.40 ± 227.90）/mm2 ） at DO, while which had significantly decreased by 32.6% （P〈 0. 05） in group IsoD3 （（604. 56 ± 65. 77）/mm/） when compared with those in group ConD3 （（896.90±78.77）/mmz） at D3. There was no significant difference between groups of SevD3 （（808.73 ± 41.27 ）/ram2） and ConD3. The expression of easpase-3 protein was increased by 195% （P 〈 0.01 ） in Iso group while which only increased by 74% （P 〈 0.05 ） in Sev group when compared with Con group. The expression of P44 and P42 of phospho-ERK1/2 protein in the hippoeami decreased by 53% （P 〈 0.01 ） and 47% （P 〈 0.01 ）） seperately in Iso group when compared with Con group, while there were no significant differences between Sev group and Con group. Conclusion 0.3 MAC isoflurane, not sevoflurane inhibits neuronal proliferation in DG of hippocampi in the neonatal rats. Inhibiting ERK1/2 phosphorylation may involve in the mechanisms of that isoflu-rane inhibits neuronal proliferation.
出处
《中华行为医学与脑科学杂志》
CAS
CSCD
北大核心
2013年第4期299-302,共4页
Chinese Journal of Behavioral Medicine and Brain Science
基金
基金项目：国家自然科学基金项目（30700787/C03030301）
广东省自然科学基金资助项目（$2011010004558）
关键词
异氟醚
七氟醚
海马
神经细胞增殖
Isoflurane
Sevoflurane
Hippoeampus
Neuronal proliferation
