Abstract：Objective: To explore the expression of Zinc alpha-2 glycoprotein (ZAG) in temporal lobe epilepsy (TLE) and its correlation with CaMKⅡ and HCN channels. Methods: Adeno associated virus vectors (AAV-ZAG and AAV-NC) were injected into the unilateral ventricle of rats. Three weeks later, Pilocarpine hydrochloride (PHCL) was intraperitoneally injected to construct a TLE model. Three days before modeling, CaMKII inhibitor KN-93 was intraperitoneally injected and randomly divided into eight groups: control group, model group, AAV-NC+model group, AAV-ZAG+model group, AAV-NC+saline group, AAV-NC+KN-93 group, AAV-ZAG+saline group, and AAV-ZAG+KN-93 group. Record the time of the first occurrence of grade IV or above epilepsy after injection of PHCL and the number of spontaneous epileptic seizures in the 5th week; Immunofluorescence detection of ZAG and GFAP expression in rat hippocampal tissue; WB detection of the expression levels of ZAG, p-CaMKII, HCN1, and HCN2 in rat hippocampal tissue. Results: The expression of ZAG in the hippocampal tissue of TLE rats was significantly downregulated (P<0.05); overexpression of ZAG in hippocampal tissue can significantly prolong the latency of TLE (P<0.05), reduce the number of seizures (P<0.05), decrease the number of GFAP positive cells (P<0.05), upregulate the expression levels of HCN1, HCN2, and p-CaMKII (P<0.05), but the addition of CaMKII inhibitors can reverse these effects. Conclusion: ZAG regulates HCN channel protein activity by promoting CaMKII phosphorylation, thereby improving TLE.
段晓梅, 肖子建, 叶青, 梁生姣, 向涛. 锌α2糖蛋白在颞叶癫痫中的表达及其与CaMKⅡ磷酸化和HCN的相关性探究[J]. 河北医学, 2025, 31(8): 1282-1289.
DUAN Xiaomei, XIAO Zijian, YE Qing, et al. The Expression of Zinc α2 Glycoprotein in Temporal Lobe Epilepsy and Its Correlation with CaMK Ⅱ Phosphorylation and HCN. HeBei Med, 2025, 31(8): 1282-1289.
[1] De MeloI S,Pacheco A L D,Dos Santos Y M O,et al.Modulation of glucose availability and effects of hypo- and hyperglycemia on status epilepticus:what we do not Know yet?[J].Mol Neurobiol,2021,58(2):505-519. [2] Wei X,Liu X,Tan C,et al.Expression and function of zinc-alpha2-glycoprotein[J].Neurosci Bull,2019,35(3):540-550. [3] Maslinska D,Laure-kamionowaka M,Maslinski S.Crosstalk in human brain between globoid cell leucodystrophy and zinc-alpha-2-glycoprotein (ZAG),a biomarker of lipid catabolism[J].Folia Neuropathol,2013,51(4):312-318. [4] Liu Y,Wang T,Liu X,et al.Neuronal zinc-alpha2-glycoprotein is decreased in temporal lobe epilepsy in patients and rats[J].Neuroscience,2017(357):56-66. [5] Benarroch E E.HCN channels:function and clinical implications[J].Neurology,2013,80(3):304-10. [6] Lee C H,Mackinnon R.Voltage sensor movements during hyperpolarization in the HCN channel[J].Cell,2019,179(7):1582-1589. [7] He J T,Li X Y,Zhao X,et al.Hyperpolarization-activated and cyclic nucleotide-gated channel proteins as emerging new targets in neuropathic pain[J].Rev Neurosci,2019,30(6):639-649. [8] Bleakley L E,Mckenzie C E,Soh M S,et al.Cation leak underlies neuronal excitability in an HCN1 developmental and epileptic encephalopathy[J].Brain,2021,144(7):2060-2073. [9] Chung W K,Shin M,Jaramillo T C,et al.Absence epilepsy in apathetic,a spontaneous mutant mouse lacking the h channel subunit,HCN2[J].Neurobiol Dis,2009,33(3):499-508. [10] Lin W,Qin J,Ni G,et al.Downregulation of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the hippocampus of patients with medial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS)[J].Hippocampus,2020,30(10):1112-1126. [11] 王颍,高伶俪,王莎,et al.丹参酮ⅡA治疗血管性痴呆作用机制研究进展[J].江苏中医药,2023,55(12):73-77. [12] 顾宇婧,张晓红,王妤婷,et al.Nrf2参与CaMKⅡ抑制引起的神经细胞毒性作用[J].解剖科学进展,2024,30(1):82-85. [13] Noam Y,Zha Q,Phan L,et al.Trafficking and surface expression of hyperpolarization-activated cyclic nucleotide-gated channels in hippocampal neurons[J].Biol Chem,2010,285(19):14724-14736. [14] 王一晰,黄柏玮.癫痫相关诱发机制及治疗方法的研究进展[J].中国实用神经疾病杂志,2024,27(9):1168-1172.
2025, Vol. 31 
冀公网安备13080202000786号