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认知相关文献学习2019-10-14-05

术后认知功能障碍（POCD）是外科手术后的常见并发症，但截止目前还没有有效的治疗方法。如果有有效的预防治疗药物或措施则对于预后有极大的帮助。这篇文献做了很好的尝试，在大鼠上利用κ阿片受体激动剂可改善POCD的症状，对临床POCD防治有一定的借鉴意义。

中文摘要

κ阿片受体激动剂可通过JAK2/STAT3信号通路改善大鼠术后认知功能障碍

术后认知功能障碍（POCD）是外科手术特别是体外循环手术（CPB）术后的常见并发症。当前没有合适的治疗方法，并且会增加患者的死亡率。

本研究旨在寻找治疗POCD的新方法。

探讨κ阿片受体（KOR）激动剂对CPB后大鼠POCD的保护作用，并研究了Janus激酶2 /信号转导和转录激活因子3（JAK2/STAT3）信号通路的调控机制。

将大鼠随机分为5组：假手术组（sham组），CPB手术组（CPB组），KOR激动剂+ CPB（K组），KOR激动剂+降冰片碱（nor-BNI）+ CPB（NK组）和KOR激动剂+ JAK2-STAT3特异性途径*制剂抑**+ CPB（AG组）。

使用水迷宫测试和神经功能评分来评估POCD。

使用苏木精和伊红染色观察海马神经元。

使用ELISA法检测炎症因子，氧化应激因子和脑损伤标记物的水平。

使用免疫荧光法观察神经元。

TUNEL染色和Western blotting用于检测神经元凋亡，Western blotting也用于检测JAK2/STAT3通路相关的蛋白。

KOR激动剂显著改善POCD。

S‑100β和NSE检测表明，KOR激动剂减轻了CPB大鼠的脑损伤，这一结果可被KOR拮抗剂逆转。

与CPB组相比，通过ELISA检测确定，KOR激动剂显著降低炎症反应和氧化应激，而TUNEL染色和Western blotting显示，KOR激动剂减轻海马神经元凋亡。

最后，与CPB组相比，KOR激动剂抑制了磷酸化（p‑）JAK2和p‑STAT3的表达水平，而不是总JAK2和STAT3的表达水平。

总之，KOR激动剂通过抑制JAK2/STAT3信号通路改善CPB大鼠的POCD。

英文摘要

Kappa opioid receptor agonists improve postoperative cognitive dysfunction in rats via the JAK2/STAT3 signaling pathway.

Postoperative cognitive dysfunction (POCD) is a common and well‑known complication following surgery, particularly cardiopulmonary bypass (CPB) surgery. There are currently no suitable treatments for POCD, which is associated with increased illness and mortality rates. The present study aimed to identify a novel treatment for POCD. The protective effect of kappa opioid receptor (KOR) agonists on POCD in rats following CPB was determined and the regulatory mechanism of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was examined. The rats were randomly divided into five groups: Sham operation (Sham group), CPB operation (CPB group), KOR agonist + CPB (K group), KOR agonist + norbinaltorphimine (nor‑BNI) + CPB (NK group), and KOR agonist + JAK2‑STAT3 specific pathway inhibitor + CPB (AG group). A water maze test and neurological function scores were used to evaluate POCD. Hematoxylin and eosin staining was used to observe hippocampal neurons. ELISA was used to detect the levels of inflammatory factors, oxidative stress factors and brain injury markers. Immunofluorescence was used to visualize the neurons. TUNEL staining and western blotting were used to detect neuronal apoptosis, and western blotting was also used to detect JAK2/STAT3 pathway‑related proteins. The KOR agonists significantly improved POCD. S‑100β and NSE detection revealed that KOR agonists alleviated brain damage in CPB rats, and this result was reversed by KOR antagonists. The KOR agonists led to a significantly reduced inflammatory response and oxidative stress, as determined by ELISA detection, and attenuated hippocampal neuronal apoptosis, as revealed by TUNEL staining and western blotting, compared with the results in the CPB group. Finally, the KOR agonists inhibited the expression levels of phosphorylated (p‑)JAK2 and p‑STAT3, rather than total JAK2 and STAT3, compared with levels in the CPB group. Taken together, KOR agonists improved POCD in rats with CPB by inhibiting the JAK2/STAT3 signaling pathway.