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目的探讨N-乙酰半胱氨酸(NAC)对内毒素(LPS)增敏的新生大鼠缺氧缺血性脑损伤(HIBD)的防治效果和作用机制。方法8日龄Wistar大鼠98只,性别不拘,其中86只随机分为3组,安慰剂组(29只)、小剂量(25 mg/kg)(31只)和大剂量(200mg/kg)NAC治疗组(26只)。新生大鼠予腹腔注射LPS(0.1 mg/kg),3 d后结扎左侧颈总动脉并吸入7.7%的氧气40 min制备成LPS增敏的HIBD动物模型。在应用LPS后1 h、缺氧缺血(HI)前2 h、HI后02、4 h腹腔注射NAC(25 mg/kg或200 mg/kg)或同体积生理盐水,HI后7 d评价脑损伤的程度。余下12只分别给予大剂量NAC(6只)和安慰剂(6只)并在HI后24 h测定脑组织Caspase-3的活性和蛋白印迹。结果大剂量NAC治疗组脑梗死体积较安慰剂组减少77%(P<0.001),而组织丢失体积均减少67%(P<0.001)。小剂量NAC治疗组脑梗死及脑组织丢失体积与对照组相比无明显差别。HI后24 h大剂量NAC治疗组Caspase-3活性较安慰剂组显著降低(53%,P<0.001)。结论NAC对LPS增敏的新生大鼠HIBD的防治作用呈剂量依赖性,其神经保护作用与抑制Caspase-3相关。
Objective To investigate the preventive and therapeutic effects and mechanism of NAC on hypoxic-ischemic brain damage (HIBD) induced by endotoxin (LPS) in neonatal rats. Methods Eighty-eight adult Wistar rats were randomly divided into three groups: placebo group (n = 29), low dose (25 mg / kg) and high dose (200 mg / NAC treatment group (26). Neonatal rats were injected intraperitoneally with LPS (0.1 mg / kg). After 3 days, the left common carotid artery was ligated and inhaled 7.7% oxygen for 40 min to prepare LPS-sensitized HIBD animal model. NAC (25 mg / kg or 200 mg / kg) or normal saline was injected intraperitoneally 1 h after hypoxia-ischemia (HI), 2 h before hypoxia-ischemia (HI) The extent of damage. The remaining 12 were given high-dose NAC (6) and placebo (6) respectively and the activity and Western blot of Caspase-3 in brain tissue were measured 24 h after HI. Results Compared with placebo group, the volume of cerebral infarction in high-dose NAC group decreased by 77% (P <0.001), while the volume of tissue loss decreased by 67% (P <0.001). Small doses of NAC treatment group cerebral infarction and brain tissue loss volume compared with the control group no significant difference. Caspase-3 activity was significantly lower in the NAC treatment group than in the placebo group at 24 h after HI (53%, P <0.001). CONCLUSION: The preventive and therapeutic effects of NAC on HIBD of LPS-sensitized neonatal rats are dose-dependent and its neuroprotective effect is related to the inhibition of Caspase-3.