Zhang J-C, Zhang W-J, Zhao Q, Chen B-N, Wang X, Luo Y-P, Zhang F-X
Department of Anesthesiology, Guizhou Provincial People's Hospital, Guiyang, China.
Eur Rev Med Pharmacol Sci. 2019 Aug;23(3 Suppl):171-176. doi: 10.26355/eurrev_201908_18644.
To investigate the intervention of exogenous adiponectin in the elderly rats with cognitive dysfunction induced by isoflurane through mitogen-activated protein kinase (MAPK) signaling pathway in hippocampus.
A total of 60 healthy elder Sprague Dawley (SD) rats aged 15-20 months and weighing 400-500 g were selected. These rats were randomly divided into four groups, i.e., the control group, the anesthetic group, adiponectin intervention group, and p38-MAPK antagonist group, in which the rats in the control group were treated through inhalation of pure oxygen for 4 h at a rate of 4 L/min, while the rats in the other 3 groups were treated through inhalation of isoflurane for 4 h. During the inhalation of isoflurane, the concentration of isoflurane was 3.5% at the beginning and decreased to 2.2% at 1 h, and 1.7% between 2 h and 4 h. Then, the intraperitoneal injection of 0.5 mL normal saline was performed for the rats in the control group and the anesthetic group, while adiponectin (300 mg/kg) was injected into the rats in the adiponectin intervention group and p38-MAPK antagonist group. Simultaneously, the antagonist (20 mg/kg) diluted to 0.5 mL was given to the rats in the p38-MAPK antagonist group, once/day for 3 days. Morris water maze test was carried out respectively in the 1st, 3rd, and 7th day, and 5 rats participated in the test at each time point, during which we recorded the escape latency, as well as the length of the swimming route of rats. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting were employed to detect the mRNA and protein expressions of p38 in the hippocampus.
The escape latency and the length of the swimming route at any time point after the intervention in the anesthetic group were significantly longer than those in the control group (p<0.05), and they were significantly shorter in the adiponectin intervention group than those in the anesthetic group (p<0.05), but there were no differences between the p38-MAPK antagonist group and the anesthetic group (p>0.05). The mRNA and protein expressions of p38 at any time point after intervention in the anesthetic group were higher than those in the control group (p<0.05), and they were significantly lower in the adiponectin intervention group than those in the anesthetic group (p<0.05), but there were no differences between the p38-MAPK antagonist group and the anesthetic group (p>0.05).
Exogenous adiponectin can improve the cognitive dysfunction of the elderly rats after anesthesia using isoflurane, possibly by inhibiting the p38-MAPK signal pathway in hippocampus.
探讨外源性脂联素通过海马组织中丝裂原活化蛋白激酶（MAPK）信号通路对异氟烷诱导的老年大鼠认知功能障碍的干预作用。
选取60只健康的15 - 20月龄、体重400 - 500 g的老年Sprague Dawley（SD）大鼠。将这些大鼠随机分为四组，即对照组、麻醉组、脂联素干预组和p38 - MAPK拮抗剂组，其中对照组大鼠以4 L/min的速率吸入纯氧4 h，而其他3组大鼠吸入异氟烷4 h。在吸入异氟烷期间，异氟烷浓度开始时为3.5%，1 h时降至2.2%，2 h至4 h期间为1.7%。然后，对照组和麻醉组大鼠腹腔注射0.5 mL生理盐水，而脂联素干预组和p38 - MAPK拮抗剂组大鼠注射脂联素（300 mg/kg）。同时，将拮抗剂（20 mg/kg）稀释至0.5 mL给予p38 - MAPK拮抗剂组大鼠，每天1次，共3天。分别在第1、3和7天进行Morris水迷宫试验，每个时间点有5只大鼠参与试验，在此期间记录逃避潜伏期以及大鼠游泳路线的长度。采用逆转录 - 聚合酶链反应（RT - PCR）和蛋白质印迹法检测海马组织中p38的mRNA和蛋白表达。
麻醉组干预后任何时间点的逃避潜伏期和游泳路线长度均显著长于对照组（p<0.05），脂联素干预组显著短于麻醉组（p<0.05），但p38 - MAPK拮抗剂组与麻醉组之间无差异（p>0.05）。麻醉组干预后任何时间点p38的mRNA和蛋白表达均高于对照组（p<0.05），脂联素干预组显著低于麻醉组（p<0.05），但p38 - MAPK拮抗剂组与麻醉组之间无差异（p>0.05）。
外源性脂联素可改善老年大鼠异氟烷麻醉后的认知功能障碍，可能是通过抑制海马组织中的p38 - MAPK信号通路实现的。
