摘要
目的初步探讨葛根素治疗对大鼠创伤性脑损伤的自噬影响以及分子机制。方法将75只成年sD大鼠按随机数字表法分为假手术组（S组）、创伤性脑损伤组（TBI组）、创伤性脑损伤＋葛根素治疗组（TBI＋Pue组）、创伤性脑损伤＋JNK选择性拮抗剂组（TBI＋SP组）以及创伤性脑损伤＋JNK激动剂＋葛根素组（TBI＋Pue＋An组）。Feeney法构建大鼠创伤性脑损伤模型。分别于模型制备后1、3、7d进行脑水含量测定以及神经功能缺陷评分。模型制备后第7天通过Westernblot法检测自噬标志蛋白LC3B和Beclin1以及JNK的磷酸化水平。结果与S组比较，其余四组在大鼠创伤模型制备后各个时间点的脑水含量与神经功能缺陷评分均明显升高（P〈0．05）；与TBI组比较，TBI＋Pne组和TBI＋sP组在各个时间点的脑水含量明显降低（P〈0．05），在模型制备后的第3天和第7天神经功能缺陷评分明显降低（P〈0．05）；而与TBI＋Pue组比较，TBI＋Pue＋An组脑水含量在模型制备后各个时间点均增加（P〈0．05），神经功能缺陷评分在模型制备后第3天和第7天均增加（P〈0．05）。与S组比较，在模型制备后第7天TBI组LC3II、Beclinl的表达明显增加（P〈0．05）；与TBI组比较，TBI＋Pue组、TBI＋sP组均明显抑制LC3II以及Beclinl的表达（P〈0．05）；而与TBI＋Pue组比较，TBI＋Pue＋An组LC3II和Beclinl表达均明显增加。与S组比较，TBI组P．JNK1／JNK1明显增加（P〈0．05）；与TBI组比较，TBI＋Pue组、TBI＋sP组的P-JNK1／JNK1明显减少（P〈0．05）；与TBI＋Pue组比较，TBI＋Pue＋An组的P-JNK1／JNK1明显增加（P〈0．05）。结论葛根素可通过抑制自噬发挥对创伤性脑损伤的保护作用，JNK通路可能是葛根素调控自噬的分子学机制。
Objective To explore the impact of puerarin treatment on autophagy in rats with trau- matic brain injury （TBI） and the underlying mechanism. Methods Seventy five Sprague-Dawley （SD） rats were randomized into 5 groups ： sham group （ S group, n = 15 ） , traumatic brain injury group （ TBI group, n = 15 ）, TBI ＋ puerarin treatment group （ TBI ＋ Pue group, n = 15 ）, TBI ＋ JNK inhibitor group （ TBI ＋ SP group, n = 15 ）, and TBI ＋ JNK activator ＋ Pue （ TBI ＋ An ＋ Pue group, n = 15 ）. Feeney meth- od was applied to make rats with TBI model. After that, head water content and neurological deficit score （NDS） were measured and recorded at day 1,3 and 7 in each group. Western blot was used to measure the JNK activity and autophagic marker proteins, including LC3B and Beclinl. Results Compared to S group, the head water content and NDS were decreased significantly among the others （ P 〈 0.05 ）. The head water content and NDS in TBI ＋ Pue and TBI ＋ SP groups was decreased remarkably compared with TBI group. Combined with puerarin and animycin treatments failed to reduce head water content and NDS compared to the TBI ＋ Pue group. Activated autophagy could be observed in TBI group compared to S group. Compared to group S, LC3II, Beclinl and P-JNK1 were increased significantly. Pue and SP could reduce their expres- sions, respectively. Combined with puerarin and animycin treatments failed to reduce LC3II, Beclinl and P-JNK1 compared to TBI ＋ Pue group. Conclusions Puerarin could protect rats with TBI via inhibiting au- tophagy, JNK signal pathway could involve the process of puerarin regulating autophagy.
作者
赵志强
王向东
郭铁柱
任新亮
Zhao Zhiqiang Wang Xiangdong Guo Tiezhu Ren Xinliang(Department of Neurosurgery, Affiliated Heft Hospital of Changzhi Medical College, Changzhi 046000, Chin)
出处
《中国医师杂志》
CAS
2017年第1期79-82,85,共5页
Journal of Chinese Physician
