目的 探讨脑苷肌肽对缺氧缺血性脑病（HIE）新生大鼠沉默信息调节因子2相关酶1（SIRT1）/哺乳动物雷帕霉素靶蛋白（mTOR）/p70核糖体蛋白S6激酶（p70S6K）通路及神经元凋亡的影响。方法 采用结扎左侧颈总动脉及缺氧玻璃仓的方法建立新生大鼠HIE模型，造模大鼠随机分为5组：模型组、脑苷肌肽低剂量组（0.8 mg/kg）、脑苷肌肽中剂量组（1.6 mg/kg）、脑苷肌肽高剂量组（3.2 mg/kg）、尼莫地平组（10 mg/kg），每组12只，另取12只设为假手术组。分组处理后，观察各组大鼠神经行为活动并进行评分；测定各组大鼠脑组织含水量；TUNEL染色检测各组大鼠脑皮质神经元凋亡情况；酶联免疫吸附法（ELISA）检测各组大鼠血清肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）水平；免疫印迹法检测各组大鼠脑组织SIRT1/mTOR/p70S6K通路相关蛋白表达情况。结果 与假手术组相比，模型组大鼠神经功能缺损评分、脑组织含水量、脑皮质神经元凋亡率、血清TNF-α及IL-1β水平、脑组织SIRT1/mTOR/p70S6K通路相关蛋白p-mTOR/mTOR及p-p70S6K/p70S6K明显升高，脑组织SIRT1表达降低（P<0.001）；与模型组相比，脑苷肌肽低、中、高剂量组及尼莫地平组大鼠神经功能缺损评分、脑组织含水量、脑皮质神经元凋亡率、血清TNF-α及IL-1β水平、脑组织SIRT1/mTOR/p70S6K通路蛋白p-mTOR/mTOR及p-p70S6K/p70S6K降低，脑组织SIRT1表达升高（P<0.001），且脑苷肌肽各组呈剂量依赖性（P<0.001），脑苷肌肽高剂量组与尼莫地平组相比，大鼠各指标差异无统计学意义。结论 脑苷肌肽可促使HIE新生大鼠脑组织SIRT1表达，降低mTOR、p70S6K磷酸化水平，抑制炎症，减轻脑水肿及神经元凋亡，修复神经功能，改善其临床症状。

Objective To investigate the effect of cattle encephalon glycoside and ignotin on sirtuin 1 (SIRT1)/mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase 1 (p70S6K) pathway and neuronal apoptosis in neonatal rats with hypoxic-ischemic encephalopathy (HIE).Methods neonatal rats HIE model were established by ligating left common carotid artery and hypoxic glass chamber, they were randomly divided into 5 groups: model group, low dose (0.8 mg/kg), medium dose (1.6 mg/kg), high dose (3.2 mg/kg) groups of cattle encephalon glycoside and ignotin, and nimodipine group (10 mg/kg), with 12 in each group, another 12 rats were set as sham operation group. After grouping, the neurobehavioral activities of rats in each group were observed and scored, the water content of brain tissue was measured, the apoptosis of cerebral cortex neurons was detected by TUNEL staining, the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA), the expression of SIRT1/mTOR/p70S6K pathway related proteins was detected by Western blotting. Results Compared with those in the sham operation group, the neurological deficit score, water content of brain tissue, apoptosis rate of cortical neurons, levels of serum TNF-α and IL-1β, SIRT1/mTOR/p70S6K pathway related proteins p-mTOR/mTOR and p-p70S6k/p70S6K pathway were significantly increased in the model group, the expression of SIRT1 in brain tissue was decreased (P < 0.001). Compared with those in the model group, the neurological deficit score, water content of brain tissue, apoptosis rate of cortical neurons, levels of serum TNF-α and IL-1β, SIRT1/mTOR/p70S6K pathway related proteins p-mTOR/mTOR and p-p70S6k/p70S6K pathway were significantly decreased in the low, medium and high dose groups of cattle encephalon glycoside and ignotin, and nimodipine group. The expression of SIRT1 in brain tissue was increased (P< 0.001), there was a dose-dependent effect in groups of cattle encephalon glycoside and ignotin (P < 0.001). There was no significant difference in each index between high-dose group of cattle encephalon glycoside and ignotin and nimodipine group. Conclusion Cattle encephalon glycoside and ignotin can promote the expression of SIRT1 in brain tissue of neonatal rats with HIE, reduce the phosphorylation levels of mTOR and p70S6K, inhibit inflammation, relieve brain edema and neuronal apoptosis, and repair nerve function and improve clinical symptoms.

R965.1

河南省科技攻关项目（LHGJ20191385）