


黄连素调控犬尿氨酸通路干预脑损伤后交感神经亢进的研究
朱丽萍,王 凌* ( 福建医科大学省立临床医学院,福建省立医院药学部,福建福州 350001) 摘要: 目的 观察黄连素对脑损伤后阵发性交感神经功能亢进( PSH) 的干预作用并探讨其作用机制。方法 大鼠分为模型组和高、低剂量给 药组,其中给药组在造模前 24 h 通过灌胃接受 2 个剂量的黄连素〔高剂量组 300mg /( kg·d) 〕,低剂量组 100mg /( kg·d) ,之后 3 组参照 Marmarou 法制作弥漫性轴索损伤模型。采用改良神经功能严重程度评分表评估大鼠神经功能缺损,ELISA 检测各组大鼠血去甲肾上腺素浓度 和炎症因子 IL-6、TNF-α、IL-1β 水平,高效液相色谱法测定血和海马色氨酸、犬尿氨酸浓度。结果 与模型组相比,高剂量黄连素明显增加色氨 酸,而减低犬尿氨酸的血、海马浓度水平,使犬尿氨酸/色氨酸大幅降低( P < 0. 001) 。低剂量黄连素对犬尿氨酸或色氨酸水平的影响明显小于高 剂量黄连素,但低剂量黄连素亦可显著降低血及海马犬尿氨酸/色氨酸比率( P < 0. 001) 。同时,高剂量黄连素还可显著改善神经功能缺损( P < 0. 001) 并下调炎症因子 IL-1β 和 TNF-α( P < 0. 001) 。结论 黄连素可以干预由脑损伤所致 PSH 的发展,其机制可能通过犬尿氨酸途径实现。 关键词: 黄连素; 犬尿氨酸; 脑损伤; 交感神经亢进 中图分类号: R965 文献标识码: A 文章编号: 1006-3765( 2022) -11-0036-05
Effect of Berberine on Sympathetic Hyperactivity after Brain Injury via Kynurenine Pathway ZHU Li-ping,WANG Ling* ( Fujian Provincial Clinical Medical College of Fujian Medical University,Department of Pharmacy,Fujian Provincial Hospital,Fuzhou 350001,China) ABSTRACT: OBJECTIVE To observe the intervention effect of berberine on paroxysmal sympathetic hyperactivity ( PSH) after brain injury and to explore the mechanism. METHODS The rats were divided into model,highdose and low-dose groups. The high-dose and low-dose groups received 2 equal doses of berberine〔300 mg /( kg· d) for the high-dose group and 100 mg /( kg·d) for the low-dose group〕by gavage 24 h before the establishment of the animal model. Then,the 3 groups were made diffuse axonal injury model according to the Marmarou method. The modified neurological severity scale was used to evaluate the neurological deficits in rats. ELISA was performed to detect the blood levels of norepinephrine and inflammatory factors such as IL-6,TNF-α and IL-1β in each group. The concentrations of tryptophan and kynurenine in blood and hippocampus were determined by high performance liquid chromatography. RESULTS Compared with the model group,high-dose berberine greatly increased the tryptophan level,but decreased the kynurenine level,thereby remarkably reducing the kynurenine /tryptophan ratio in blood and hippocampal ( P < 0. 001) . The effect of low-dose berberine on the level of kynurenine or tryptophan was significantly less than that of high-dose berberine,but low-dose berberine could also markedly reduced the ratio of kynurenine / tryptophan in blood and hippocampus ( P < 0. 001) . Meanwhile,high-dose berberine could dramatically improve neurological deficits ( P < 0. 001) and down-regulate IL-1β and TNF-α ( P < 0. 001) . CONCLUSION Berberine can inhibit the development of PSH caused by brain injury,which may be achieved through kynurenine pathway. KEY WORDS: Berberine; Kynurenine; Brain damage; Sympathetic hyperactivity
黄连素调控犬尿氨酸通路干预脑损伤后交感神经亢进的研究 .pdf