目的:观察全麻/控制性降压手术对海马神经元损伤的影响及其可能的机制.方法:选用12只6～8月龄雄性健康比格犬,随机分为全麻组(A组,n=6)和控压组(C组,n=6).全麻组采用丙泊酚注射及异氟醚吸入麻醉,控压组在麻醉基础上联合硝普钠行控制性降压,达到目的血压(基础平均动脉压的40％)后维持60 min(2组动物均在相应期间行剖腹探查术),术毕使血压回升至基础水平72 h后取脑.采用免疫组织化学法检测海马CA1和CA3区白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)以及凋亡相关蛋白(Bcl-2、Bax和活化型caspase-3)的表达；TUNEL法检测海马神经元凋亡情况.结果:(1)控压组动物海马CA1和CA3区IL-1β和TNF-α阳性细胞率均较全麻组升高(P＜0.01)；(2)控压组CA1和CA3区Bcl-2/Bax阳性细胞比值均较全麻组降低(P＜0.05)；与此相应,控压组海马各区caspase-3阳性细胞率均显著高于全麻组(P＜0.01)；(3)全麻组与控压组CA1和CA3区存在凋亡细胞,但控压组各区细胞凋亡指数均较全麻组显著升高(P＜0.01).结论:全麻/控制性降压下的手术可诱导海马不同区域促炎细胞因子表达,降低Bcl-2/Bax比值,促进caspase-3的表达,进而导致海马神经元的凋亡.这种术后海马神经元损伤可能与全麻/控压手术诱导的海马炎症反应有关.%AIM: To observe the influence and the possible mechanism of surgical operation with general anesthesia/controlled hypotension on neuronal injury in hippocampus. METHODS: Twelve healthy male Beagle dogs aged 6 ~ 8 months were randomly divided into general anesthesia group ( group A, n = 6) and controlled hypotension group (group C, n = 6). The dogs in group A were anesthetized with propofol injection and isoflurane inhalation. The dogs in group C were combined with intravenous infusion of sodium nitroprusside to induce hypotension based on the anesthesia, and the target mean arterial pressure (MAP) was maintained at 40% of the baseline level for 1 h. The animals in both groups underwent exploratory laparotomy in the corresponding period. MAP was controlled to return to baseline level after surgery, and then the brain tissues were taken out 72 h later. The levels of IL-1β, TNF-α, Bcl-2, Bax and cleaved caspase-3 were measured by the method of immunohistochemistry, and neuronal apoptosis was detected by TUNEL in CA1 and CA3 regions of hippocampus. RESULTS: The ratios of IL-1β and TNF-α positive cells in CA1 and CA3 regions of hippocampus were significantly increased in group C than those in group A. The ratio of Bcl-2/Bax in CA1 and CA3 regions of hippocampus was lower in group C than that in group A. In contrast, the ratio of caspase-3 positive cells in group C was significantly higher than that in group A. The apoptotic index of hippocampal neurons in group C was significantly higher than that in group A. CONCLUSION: The exaggerated expression of proinflammatory cytokines in hippocampus may be induced by surgical operation with general anesthesia/controlled hypotension, leade to reduce the Bcl-2/Bax ratio, and to promote the expression of caspase-3, so as to resulting in neuronal apoptosis in hippocampus. These results suggest that postoperative neuronal damage may be related to hippocampal neuro-inflammation caused by surgical operation with general anesthesia/controlled hypotension.
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