Effects Of Trillium Tschonoskii Maxim On Cognitive Function In VCI Rats Through ERS Regulation Of NLRP3 Inflammasome

To explore the effect and mechanism of Trillium Tschonoskii Maxim on the learning and memory ability of vascular cognitive impairment rats by regulating ERS and inhibiting NLRP3 inflammatory activity.Methods: Forty SD rats were randomly divided into sham operation group(sham group),model group(VCI group),TTM group(TTM group,100 mg / kg)and Donepezil Hydrochloride group(Positive group,0.45 mg / kg),10 rats in each group.The VCI model was prepared by bilateral common carotid artery ligation in all groups except the Sham group.On the second day after modeling,the rats were intragastrically administered.The TTM group was intragastrically administered at 100 mg / kg,the Positive group was intragastrically administered at 0.45 mg / kg,and the Sham group and the VCI group were intragastrically administered with the same volume of double distilled water.After 28 days of continuous intragastric administration,the learning and memory ability of rats in each group was detected by water maze and new object recognition.HE staining was used to detect the morphological changes of neurons in hippocampal CA1 region,and the number and distribution of Nissl bodies were detected by Nissl staining.Western Blot was used to observe the expression of endoplasmic reticulum stress-related proteins IRE1,GRP78 / Bip,XBP-1 and inflammasome-related proteins NLRP3,ASC,Caspase-1,interleukin 1β(IL-1β)and interleukin 18(IL-18)in hippocampus.Results:1.Behavioral test results : Compared with Sham group,the escape latency of rats in VCI group was significantly prolonged,the number of crossing the survival platform was reduced,the time ratio of the target quadrant to the total time was shortened,and the new object recognition index was decreased(P <0.01).Compared with the VCI group,the escape latency of the TTM intervention group and the Positive control group was shortened,the number of crossing platforms was increased,the ratio of target quadrant residence time to total time was increased,and the new object recognition index was increased(P < 0.05 or P < 0.01).There was no significant difference in the number of crossing platforms between the Positive group and the VCI group(P > 0.05).2.Histological detection results :(1)HE staining results : The cells in the hippocampus of the Sham group were normal in morphology,neatly arranged,rich in cytoplasm and nucleus,and abundant in neurons;compared with Sham group,the hippocampal CA1 region of rats in VCI group showed cell damage,morphological destruction,obvious nuclear pyknosis and decreased number of hippocampal neurons.Compared with the VCI group,the TTM intervention group and the Positive control group showed significantly reduced cell damage,nuclear condensation,and significantly increased number of neurons.(2)Nissl staining results : Compared with the Sham group,the number of Nissl bodies in the hippocampal CA1,DG and CA3 regions of the VCI group decreased,the arrangement was loose,and the gap between the cell bodies was larger;compared with the VCI group,the number of Nissl bodies in the TTM intervention group and the Positive control group increased significantly,arranged neatly,and the intercellular space was small.3.Western Blot test results :(1)Endoplasmic reticulum related protein IRE1,GRP78 / Bip,XBP-1 results : Compared with Sham group,the expression of IRE1,GRP78 / Bip and XBP-1 in VCI group increased(P < 0.05 or P <0.01);compared with VCI group,the expression of IRE1,GRP78 / Bip and XBP-1 in TTM intervention group and Positive group decreased(P < 0.05 or P < 0.01).There was no significant difference in IRE1 between Positive group and VCI group(P >0.05).(2)NLRP3 inflammasome-related protein detection results : Compared with Sham group,the expression of NLRP3,ASC,Caspase-1,IL-18 and IL-1β protein in hippocampus of VCI group was significantly increased(P < 0.01).Compared with VCI group,the expression of inflammatory factors in TTM intervention group and Positive group decreased significantly(P < 0.05 or P < 0.01).Conclusion:Trillium Tschonoskii Maxim can improve the learning and memory of VCI rats,and its mechanism may be related to the regulation of NLRP3 inflammasome activity by ERS.