| Objective:Objective to explore the mechanism of Huanglian Jiedu Decoction on learning and memory and brain inflammation in Alzheimer’s disease(AD)rats by regulating cholinergic nerve related protein.Method:Sixty male SD rats were selected and divided into three groups:normal group,model group,huperzine a group(2.1×10-5g·kg-1),and high,medium,and low-dose groups of Huanglian Jiedu Decoction(6,3,and 1.5 g·kg-1).Except for the normal group,rats in each group were given bilateral injections of Aβ1-42 in the hippocampal CA1 region to replicate the ad model.The normal group was injected with an equal volume of control solvent.Administration was continued for 28 days postoperatively.At the end of the feeding period,the learning and memory abilities of the rats were assessed by Morris water maze test,the pathological changes in the hippocampus were observed by hematoxylin eosin(HE)staining,and Enzymelinked(ELISA)immunosorbent assay to detect interleukin(IL)-1β,IL-6,IL-8,IL10,tumor necrosis factor(TNF)-α,acetylcholine(ACh),acetylcholinesterase(AChE),choline acetyltransferase(ChAT)in rat serum and hippocampus;Western blotting The expression of hippocampal α7nAChR protein was detected;real-time fluorescent quantitative,PCR was used to detect the expression of hippocampal α7nAChR mRNA.Result:Compared with the sham operation group,HE staining showed that the pathological changes such as neuronal necrosis in the cortex of the brain tissue,necrosis of pyramidal cells or granular cells in the hippocampus,disordered arrangement and infiltration of inflammatory cells in the model group were obvious.The escape latency of rats was prolonged and escaped.Decrease in the number of platforms,staying time in the effective area,and swimming paths in the effective area(P<0.05,P<0.01),The concentration of IL-1β and TNF-α in rat serum was significantly increased(P<0.01);The concentration of IL-1β,IL-6 and TNF-α in hippocampal homogenate increased significantly(P<0.01);The concentration of ACh and ChAT in serum decreased(P<0.01),and the concentration of ACh,AChE,ChAT,α7nAChR,andα7nAChR mRNA in the hippocampus decreased(P<0.01).Compared with the model group,the Huanglian Jiedu Decoction medium-dose group has shorter escape latency(P<0.05),and the number of escape platforms,swimming paths in the effective area,and stay time in the effective area increased(P<0.05,P<0.01).The concentration of IL1β and TNF-α in the hippocampal homogenate of rats in the Huanglian Jiedu Decoction high-dose group decreased(P<0.05),and the concentration of IL-10 increased(P<0.05);The concentration of TNF-in the hippocampus homogenate of the rats in the Huanglian Jiedu Decoction group was reduced(P<0.05);the concentration of IL-1βand IL-6 in the hippocampus homogenate of the rats in the high-dose group was significantly reduced(P<0.01);the middle-dose group The concentration of IL-6 and IL-1β in rat hippocampal homogenate decreased significantly(P<0.01,P<0.05);serum ACh,ChAT and hippocampal ACNE,ChAT,α7nAChR mRNA levels increased(P<0.05),hippocampal α7nAChR protein expression Increased significantly(P<0.01);In the high-dose group,the effective area stayed longer(P<0.01);the number of escape platforms increased,and the serum ACh,ChAT,hippocampal ACh,AChE,α7nAChR protein,and α7nAChR mRNA levels increased(P<0.05).Conclusions:Huanglian Jiedu Decoction can significantly improve the learning and memory impairment of AD rats induced by Aβ1-42,and its mechanism of action may be related to improving the cholinergic system damage caused by Aβ1-42,enhancing the function of the cholinergic system,and thereby enhancing the cholinergic system Anti-inflammatory effect,reduce brain damage caused by neuroinflammation. |
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