目的：探讨养血清脑颗粒对帕金森综合征(PD)大鼠认知功能障碍及PERK/ATF4/CHOP通路的影响。方法：SD大鼠颈背部皮下注射鱼藤酮诱导PD大鼠模型，随机分为模型组、养血清脑低剂量(1.6 g·kg^-1)组、养血清脑中剂量(3.2 g·kg^-1)组、养血清脑高剂量(6.4 g·kg^-1)组、美多芭(100 mg·kg^-1)组，每组12只。另取12只大鼠颈背部皮下注射等剂量葵花油，设为对照组。给药后，以阿扑吗啡诱导大鼠旋转行为，比较其转圈次数；以Morris水迷宫实验评测大鼠认知功能，比较其逃避潜伏期与跨越原平台次数；以试剂盒测量大鼠脑组织多巴胺转运体(DAT)、酪氨酸羟化酶(TH)及血清炎症因子γ-干扰素(IFN-γ)、白细胞介素-18(IL-18)含量；HE染色检测大鼠海马神经细胞病理形态；蛋白质印迹(Western blotting)实验检测大鼠脑组织PERK/ATF4/CHOP通路蛋白表达。结果：与对照组相比，模型组大鼠海马神经细胞皱缩变小，细胞核形状不规则，排列散乱且数目显著减少，整体神经细胞损伤严重，转圈次数，血清IFN-γ及IL-18含量，脑组织PERK、ATF4及CHOP蛋白表达水平，逃避潜伏期显著升高，脑组织DAT及TH含量、跨越原平台次数显著降低，差异有统计学意义(P＜0.05)；与模型组相比，养血清脑低、中、高剂量组及美多芭组大鼠海马神经细胞损伤减轻，转圈次数，血清IFN-γ及IL-18含量，脑组织PERK、ATF4及CHOP蛋白表达水平，逃避潜伏期降低，脑组织DAT及TH含量、跨越原平台次数升高，养血清脑各组之间呈剂量依赖性，差异有统计学意义(P＜0.05)；养血清脑高剂量组与美多芭组相比，大鼠各指标均无明显差异(P＞0.05)。结论：养血清脑颗粒可抑制炎症发生，减轻PD大鼠海马及脑组织多巴胺能神经细胞损伤，改善大鼠运动功能，提高其认知能力，该作用机制可能与抑制PERK/ATF4/CHOP通路有关。

[1] 蒋欢,张润娉.长链非编码RNA MEG3通过靶向miR-488-3p调控帕金森病发生发展的分子机制研究[J].现代医学,2021,49(7):769-775.
[2] 谭晓琳,张立新,张志强,等.血管性帕金森综合征患者认知与运动功能相关性分析[J].现代医学,2017,45(10):1408-1412.
[3] MAROGIANNI C,SOKRATOUS M,DARDIOTIS E,et al.Neurodegeneration and inflammation-an interesting interplay in Parkinson's disease[J].Int J Mol Sci,2020,21(22):8421-8435.
[4] 樊志刚,高丽,师瑞红.干细胞移植对帕金森病大鼠的旋转行为和肿瘤坏死因子α及白细胞介素-4的影响[J].河南医学高等专科学校学报,2020,32(5):473-477.
[5] TIAN J H,WU Q,HE Y X,et al.Zonisamide,an antiepileptic drug,alleviates diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress[J].Acta Pharmacol Sin,2021,42(3):393-403.
[6] WANG H,DOU S,ZHU J,et al.Ghrelin mitigates MPP+-induced cytotoxicity:involvement of ERK1/2-mediated Nrf2/HO-1 and endoplasmic reticulum stress PERK signaling pathway[J].Peptides,2020,133(7):170374-170390.
[7] 叶海森,陈曦,李韧娇,等.养血清脑颗粒对认知功能障碍大鼠学习,记忆及GAP-43,PSD-95表达的影响[J].世界中医药,2020,15(7):80-83.
[8] 李晓霞,胡佳,黄惠英,等.养血清脑颗粒对帕金森病日间过度嗜睡患者的相关性研究[J].医药前沿,2018,8(30):293-294.
[9] 郭森,张硕,付慧霄,等.姜黄素对帕金森模型大鼠损伤神经元的修复作用及相关机制研究[J].中风与神经疾病杂志,2021,38(2):128-131.
[10] 常学辉,张良芝,李天佛.龟羚帕安丸对帕金森病大鼠中脑黑质病理、Beclin1、P62及LC3Ⅱ影响的研究[J].中华中医药学刊,2021,39(1):5-7.
[11] YANG X,ZHANG W,WU H,et al.Downregulation of CDK5 restores sevoflurane-induced cognitive dysfunction by promoting SIRT1-mediated autophagy[J].Cell Mol Neurobiol,2020,40(6):955-965.
[12] CHOHAN M O,ESSES S,HAFT J,et al.Altered baseline and amphetamine-mediated behavioral profiles in dopamine transporter Cre (DAT-Ires-Cre) mice compared to tyrosine hydroxylase Cre (TH-Cre) mice[J].Psychopharmacology (Berl),2020,237(12):3553-3568.
[13] STÖGBAUER J,ROSAR F,DILLMANN U,et al.Striatal dopamine transporters and cognitive function in Parkinson's disease[J].Acta Neurol Scand,2020,142(4):385-391.
[14] HIRSCH E C,STANDAERT D G.Ten unsolved questions about neuroinflammation in Parkinson's disease[J].Mov Disord,2021,36(1):16-24.
[15] 郭大伟,白月.盐酸多奈哌齐片联合养血清脑颗粒对脑小血管病所致血管性认知功能障碍患者hs-CRP、Hcy、脑血流灌注和电生理的影响[J].现代中西医结合杂志,2019,28(4):352-356.
[16] 许玉红.养血清脑颗粒联合艾地苯醌治疗血管性痴呆的临床研究[J].现代药物与临床,2020,35(10):2019-2022.
[17] YAMAWAKI R,NANKAKU M,KUSANO Y,et al.Evaluation of cognitive function in relation to progression of Parkinson disease[J].Am J Phys Med Rehabil,2020,99(7):626-629.
[18] HALL S,JANELIDZE S,SUROVA Y,et al.Cerebrospinal fluid concentrations of inflammatory markers in Parkinson's disease and atypical parkinsonian disorders[J].Sci Rep,2018,8(1):13276-13284.
[19] WU F,ZHANG R,FENG Q,et al.(-)-Clausenamide alleviated ER stress and apoptosis induced by OGD/R in primary neuron cultures[J].Neurol Res,2020,42(9):730-738.
[20] WANG Q,XIN X,WANG T,et al.Japanese encephalitis virus induces apoptosis and encephalitis by activating the PERK pathway[J].J Virol,2019,93(17):e00887-e00903.