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评价重复麻醉给药对实验性阿尔茨海默病大鼠脑组织和认知功能的影响。

Evaluation of the Effects of Repetitive Anaesthesia Administration on the Brain Tissues and Cognitive Functions of Rats with Experimental Alzheimer's Disease.

机构信息

Department of Anesthesiology and Reanimation, Gazi University Faculty of Medicine, 06500 Ankara, Türkiye.

Department of Physiology, Kutahya Health Sciences University Faculty of Medicine, 43020 Kutahya, Türkiye.

出版信息

Medicina (Kaunas). 2024 Aug 5;60(8):1266. doi: 10.3390/medicina60081266.

DOI:10.3390/medicina60081266
PMID:39202547
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11356554/
Abstract

We evaluated the effects of repeated ketamine, propofol, and ketamine + propofol administration on cognitive functions and brain tissue of elderly rat models with streptozotocin-induced Alzheimer's disease. Thirty elderly male Wistar Albino rats were divided into five groups: control (Group C), Alzheimer's (Group A), Alzheimer's + ketamine (Group AK), Alzheimer's + propofol (Group AP), and Alzheimer's + propofol + ketamine (Group APK). Alzheimer's disease was induced in Groups A, AK, AP, and APK via intracerebroventricular streptozotocin. Four weeks after surgery, ketamine, propofol, and ketamine + propofol were administered intraperitoneally for 3 days to Groups AK, AP, and APK, respectively. The radial arm maze test (RAMT) was performed in the initial, 1st, 2nd, 3rd, and 4th weeks after surgery and daily following anaesthesia. Blood and brain tissue samples were obtained. The RAMT results of Groups A, AK, AP, and APK decreased compared to Group C 2 weeks after Alzheimer's disease onset. Compared to Group A, the RAMT results increased in Groups AK and APK after the first anaesthesia, and in Group AP after the second anaesthesia. Brain tissue paraoxonase-1 (PON-1) and catalase (CAT) activities were low, and the thiobarbituric acid reactive substance (TBARS) level was high in Group A compared to Group C. TBARS levels of Groups AP and APK were lower than Group A, while CAT activity was higher. PON-1 activity was higher in Groups AK, AP, and APK than in Group A. Histopathological changes decreased in Groups AP and AK. A decrease in p53 was found in Group C compared to Group A. Ketamine and propofol were found to be effective at Bcl-2 immunoexpression, but a decrease in Caspase-3 was observed in Group APK. GFAP immunoexpression increased in Group A compared to Group C and in Group AP compared to Group AK. Repetitive anaesthesia application was found to positively affect cognitive functions. This was supported by histopathological and biochemical markers.

摘要

我们评估了重复使用氯胺酮、丙泊酚和氯胺酮+丙泊酚对链脲佐菌素诱导的阿尔茨海默病老年大鼠模型的认知功能和脑组织的影响。 30 只老年雄性 Wistar 白化大鼠被分为五组:对照组(C 组)、阿尔茨海默病组(A 组)、阿尔茨海默病+氯胺酮组(AK 组)、阿尔茨海默病+丙泊酚组(AP 组)和阿尔茨海默病+丙泊酚+氯胺酮组(APK 组)。A、AK、AP 和 APK 组通过侧脑室注射链脲佐菌素诱导阿尔茨海默病。手术后 4 周,分别对 AK、AP 和 APK 组腹腔内注射氯胺酮、丙泊酚和氯胺酮+丙泊酚 3 天。手术 1 周后,每周进行一次放射臂迷宫测试(RAMT)。手术后第 2、3、4 周及麻醉后每天进行 RAMT。采集血液和脑组织样本。 与 C 组相比,A、AK、AP 和 APK 组在阿尔茨海默病发病后 2 周 RAMT 结果下降。与 A 组相比,AK 和 APK 组在第一次麻醉后 RAMT 结果增加,AP 组在第二次麻醉后 RAMT 结果增加。与 C 组相比,A 组脑组织对氧磷酶-1(PON-1)和过氧化氢酶(CAT)活性降低,硫代巴比妥酸反应物质(TBARS)水平升高。AP 和 APK 组的 TBARS 水平低于 A 组,而 CAT 活性升高。AK、AP 和 APK 组 PON-1 活性高于 A 组。与 A 组相比,AP 和 AK 组的组织病理学变化减少。与 A 组相比,C 组 p53 减少。氯胺酮和丙泊酚对 Bcl-2 免疫表达有效,但在 APK 组观察到 Caspase-3 减少。与 C 组相比,A 组 GFAP 免疫表达增加,与 A 组相比,AP 组 GFAP 免疫表达增加。 重复麻醉应用被发现对认知功能有积极影响。这得到了组织病理学和生化标志物的支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce5/11356554/7a58b76f38d1/medicina-60-01266-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce5/11356554/92a37ad7bc64/medicina-60-01266-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce5/11356554/7a58b76f38d1/medicina-60-01266-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce5/11356554/92a37ad7bc64/medicina-60-01266-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce5/11356554/7a58b76f38d1/medicina-60-01266-g002.jpg

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(R)-ketamine as prophylactic and therapeutic drug for neurological disorders: Beyond depression.(R)-氯胺酮作为预防和治疗神经障碍的药物:超越抑郁症。
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