Study On The Inflammatory Mechanism Of The Protective Effect Of XueShuanXinMaiNing On Vascular Dementia Rats

Objective:Vascular dementia(VD)is one of the common types of dementia,and is a clinical syndrome of the acquired intellectual disability caused by cerebrovascular disease.Currently,drugs,acupuncture and electrical stimulation are mainly used in clinical treatment.There is a certain improvement in cognitive impairment,but no significant breakthrough has been made.Therefore,the search for safer,more reasonable and effective drugs is the main research direction.Xue Shuan Xin Mai Ning(XSXMN)is made up by dozens of authentic and precious medicines,including salvia root,Ligusticum wallichii,bezoar,musk,Ginsenosid Re and so on,mainly used for clinical diseases such as coronary heart disease,angina pectoris,cerebral infarction therapy.Previous experimental studies in this research group has found that XSXMN can improve the learning and memory ability of VD rats,and its mechanism may be related to reducing free radical damage and improving acetyl choline content.This study will further confirm the protective effect of XSXMN on VD rats,and explore its mechanism of action from the aspect of inflammatory factors.Methods:The VD rat were made by blocking bilateral common carotid arteries permanently.The experiment were divided into control group,model group,positive drug group(Co-dergocrine Mesylate Tablets,0.54 mg/kg)and XSXMN low,middle and high dose groups(0.55 g/kg,1.10 g/kg,2.20 g/kg).Rats were orally administrated with drugs for 9 weeks.Through space recognition ability(water maze)and detection ability of passive avoidance(platform),analyze its learning and memory ability.Pathological examination showed the pathological morphology of the hippocampus and cortical area.The levels of inflammatory Interleukin-10(IL-10),Interleukin-1?(IL-1?),Tumor necrosis factor-?(TNF-?)and Transforming growth factor-?1(TGF-?1)in brain tissues were detected by enzyme-linked immunosorbent assay(ELISA).The expressions of Interleukin-6(IL-6),Tumor necrosis factor-?(TNF-?),Nuclear factor-?BP65(NF-?BP65)and Glial fibrillary acidic protein(GFAP)in hippocampus of brain tissue were detected by immunohistochemical method.Result:1 Behavioral experiments1.1 water maze experiment Compared with the model group,the distance to platform of rats in XSXMN low dose group(0.55 g/kg)shortened on the 6th day(P<0.05);the latency and distance to platform of rats in middle and high dose groups(1.10 g/kg,2.20 g/kg)shortened on the 3rd to 6th day(P<0.01 or P<0.05).Starting angle and average velocity to platform had no significant changes from the 1st to 6th day.On the 7th day,every does of XSXMN groups,times of passing platform and times of passing effective area had a significant increase within 2 minutes(P<0.01 or P<0.05).The distance of staying in effective area,time of staying in effective area and time of staying in effective area/total time of rats in XSXMN low dose group had a significant increase(P<0.05).The distance of staying on platform,time of staying on platform,distance of staying in effective area,time of staying in effective area,time of staying on platform/total time,distance of staying on platform/total distance,time of staying in effective area/total time and distance of staying in effective area /total distance of rats in XSXMN middle and high dose groups had a significant increase(P<0.01 or P<0.05).1.2 platform experiment Compared with the model group,The latency of VD rats jumped off the platform and error times in XSXMN low and middle dose groups had no significant changes(0.55 g/kg,1.10 g/kg).The latency of VD rats jumped off the platform in XSXMN high dose group(2.20 g/kg)had a significant extended(P<0.05).2 Enzyme linked immunosorbent assay Compared with the model group,the content of IL-1? and IL-10 in the brain tissues of the XSXMN low,middle and high dose groups(0.55 g/kg,1.10 g/kg,2.20g/kg)was significantly decreased(P<0.01).The content of TNF-? in the brain tissues of XSXMN middle and high dose groups(1.10 g/kg,2.20 g/kg)was significantly reduced(P<0.01 or P<0.05).The content of TGF-?1 in rat brain tissue of XSXMN high dose groups(2.20 g/kg)was significantly decreased(P<0.05).3 Pathological examination The results showed that XSXMN middle and high does groups(1.10 g/kg,2.20g/kg)could mitigate the damage of cerebral cortex and hippocampus in VD rats.4 Immunohistochemical experiments Compared with the model group,the number of IL-6,NF-?BP65,TNF-? and GFAP positive cells in the hippocampus tissues of XSXMN low,middle and high does groups(0.55 g/kg,1.10 g/kg,2.20 g/kg)was reduced by different degrees(P<0.01).Conclusion:It was further confirmed that XSXMN was therapeutic on VD rats,and its mechanism was related to the inhibition of inflammatory response.