Department of Nuclear Medicine, The First Hospital of China Medical University, Shenyang, China.
Department of Nuclear Medicine, Nanjing Drum Tower Hospital, Nanjing, China.
Nicotine Tob Res. 2020 May 26;22(6):919-924. doi: 10.1093/ntr/ntz126.
The main objective of this study was to explore the mechanism of nicotine improving cognitive impairments in ischemic rats.
Twenty adult male Sprague-Dawley (SD) rats underwent ischemic model surgery by injecting endothelin-1 into the left thalamus, which were classified into four different groups with different intervention: nicotine (1.5 mg/kg/d), dihydro-β-erythroidine (DHβE; 3 mg/kg/d), nicotine (1.5 mg/kg/d) + DHβE (3 mg/kg/d), or saline, after ischemic model surgery. Another five male SD rats also underwent same surgery, while not injecting endothelin-1 but saline, as the control group. Morris water maze (MWM) test was adopted to assess the cognition. All the rats underwent the MWM test, micro positron emission tomography imaging with 2-[18F]-A-85380, and messenger RNA (mRNA) test of α 4 nicotinic acetylcholine receptor (nAChR), β 2 nAChR, tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6.
The MWM test showed the rats given nicotine showing better memory than ischemic rats (p < .05), whereas the rats given DHβE or both nicotine and DHβE did not show any statistical difference from the ischemic rats (p > .05). Micro positron emission tomography imaging showed higher uptake of tracer in the left thalamus and whole brain in rats given nicotine than in ischemic rats, but the rats given DHβE or both nicotine and DHβE did not. By real-time PCR test, the mRNA of α 4 nAChR and β 2 nAChR in rats given nicotine increased significantly compared with ischemic rats and decreased TNF-α, IL-1β, and IL-6 mRNA (all ps < .05).
By activating α 4β 2 nAChRs, nicotine plays a role in inhibiting the inflammatory factors, which contributes to improving cognitive impairment in ischemic rats.
It is well acknowledged that vascular cognitive impairment (VCI) is the second most common cause of dementia after Alzheimer's disease. Cholinergic agents have potential for the symptomatic treatment of the cognitive symptoms of dementia, but the exact mechanism still remains unclear. There are potential complex associations and interactions between VCI and inflammation. This study showed that nicotine had anti-inflammatory potency, which is most likely because of the activation of the nAChRs. By activating α4β2 nAChRs, nicotine played a role in inhibiting the inflammatory factors, which contribute to improving cognitive impairment in ischemic rats.
本研究的主要目的是探讨尼古丁改善缺血性大鼠认知障碍的机制。
20 只成年雄性 Sprague-Dawley（SD）大鼠通过向左侧丘脑注射内皮素-1 进行缺血模型手术，将其分为四组进行不同的干预：尼古丁（1.5mg/kg/d）、二氢-β-育亨宾（DHβE；3mg/kg/d）、尼古丁（1.5mg/kg/d）+DHβE（3mg/kg/d）或生理盐水，在缺血模型手术后。另外 5 只雄性 SD 大鼠也进行了相同的手术，但未注射内皮素-1，而是注射生理盐水，作为对照组。采用 Morris 水迷宫（MWM）测试评估认知能力。所有大鼠均接受 MWM 测试、2-[18F]-A-85380 微正电子发射断层扫描成像和α4 烟碱型乙酰胆碱受体（nAChR）、β2 nAChR、肿瘤坏死因子-α（TNF-α）、IL-1β 和 IL-6 的信使 RNA（mRNA）测试。
MWM 测试显示，给予尼古丁的大鼠比缺血大鼠的记忆力更好（p<0.05），而给予 DHβE 或尼古丁和 DHβE 两者的大鼠与缺血大鼠相比无统计学差异（p>0.05）。微正电子发射断层扫描成像显示，给予尼古丁的大鼠左侧丘脑和全脑的示踪剂摄取量高于缺血大鼠，但给予 DHβE 或尼古丁和 DHβE 两者的大鼠则没有。通过实时 PCR 测试，与缺血大鼠相比，给予尼古丁的大鼠的α4 nAChR 和β2 nAChR mRNA 显著增加，TNF-α、IL-1β 和 IL-6 mRNA 减少（均 p<0.05）。
通过激活α4β2 nAChRs，尼古丁在抑制炎症因子方面发挥作用，有助于改善缺血性大鼠的认知障碍。
众所周知，血管性认知障碍（VCI）是仅次于阿尔茨海默病的第二大痴呆症病因。胆碱能药物具有治疗痴呆症认知症状的症状性治疗潜力，但确切机制仍不清楚。VCI 与炎症之间存在潜在的复杂关联和相互作用。本研究表明，尼古丁具有抗炎作用，这很可能是由于 nAChRs 的激活。通过激活α4β2 nAChRs，尼古丁在抑制炎症因子方面发挥作用，有助于改善缺血性大鼠的认知障碍。
