| Part One: Systematic evaluation of Yiqi Bushen method on patients with diabetic cognitive dysfunction.Objective: Meta analysis was used to systematically evaluate the clinical efficacy of Yiqi Bushen method in patients with diabetic cognitive dysfunction.Methods: CNKI,Wanfang Data Knowledge Service Platform,Sino Med,Pub Med,Cochrane Library,Embase and other databases were searched by Internet.All randomized controlled trials(RCT)of Yiqi Bushen method in the treatment of diabetic cognitive dysfunction from their establishment to February 18,2022 were included.According to the inclusion and exclusion criteria,two reviewers independently analyzed and included studies that met the criteria.Review Manager 5.4 and Stata 16.0 were used for statistical analysis.Results: A total of 16 RCT studies including 1041 patients were included.The results showed that compared with the control group,Yiqi B ushen method could improve the clinical total effective rate of patients with diabetic cognitive dysfunction [OR=4.55,95%CI(2.99,6.91),Z=7.09,P<0.01],and improve the results of Mo CA score [MD=1.46,95%CI(0.64,2.28),Z=3.48,P<0.01].Improvement of MMSE score [MD=2.04,95%CI(0.92,3.15),Z=3.58,P<0.01].Conclusion: Compared with the conventional western medicine treatment,Yiqi Bushen therapy can better improve the cognitive function of patients with diabetic cognitive dysfunction,which is worthy of promotion.However,the included literature has less description of adverse reactions and shedding,and the overall quality of the study is low.More central and large sample clinical trials are needed to supplement the analysis.Part Two: Study on the intervention effect of Yiqi Bushen Recipe on metabolomics in hippocampus of diabetic rats.Objective: Under the guidance of clinical experience,the intervention of Yiqi Bushen Recipe on neurotransmitter metabolism in hippocampus of diabetic rats was studied in depth.Methods: Forty male Sprague Dawley rats were randomly divided into normal control group(NC group),model group(DM group),low dose group(L group)and high dose group(H group),with 10 rats in each group.The rats in DM group,L group and H group were intraperitoneally injected with 1% streptozotocin(STZ)diluted by sodium citrate solution,and NC group was injected with the same amount of sodium citrate solution.After successful modeling,rats in L group and H group were gavaged with 200mg/kg/d and 800mg/kg/d respectively,and rats in NC group and DM group were gavaged with the same volume of sterile water daily for 8 weeks.During the experiment,the changes of body weight,blood glucose,mental state,hair color,diet and stool of rats were observed and recorded.After intragastric administration,rats were evaluated by Morris water maze test.After the Morris water maze experiment,the materials were collected.The left hippocampus of rats was separated and stored in-80℃ refrigerator to observe the metabolism of neurotransmitters by liquid chromatography-mass spectrometry(LC-MS).The right brain of rats was fixed in 4%paraformaldehyde solution,followed by paraffin embedding and hematoxylin-eosin staining to observe the pathological changes of brain tissue.Results:1.General status: in the course of the experiment,compared with NC group rats,DM group rats drinking water,food intake and urine volume increased significantly,loose stools,dark hair color,weight loss,and depressed,sluggish response;the symptoms of the model group also appeared in the early stage in the L group and H group,but the symptoms were alleviated after treatment.2.Body weight results: before modeling,there was no significant difference in body weight of rats in each group(P>0.05).After successful modeling,the body weight of DM group,H group and L group decreased to varying degrees.After intragastric administration,the body weight of DM group,H group and L group was significantly different from that of NC group(P<0.01).At week 2 and 4,there was no significant difference in body weight between group H and L compared with DM group(P>0.05).In the 6th week,compared with DM group,the weight difference in H group was statistically significant(P<0.05).At the 8th week,compared with DM group,the weight difference between group H and L was statistically significant(P<0.05).3.Blood glucose results: after rapid intraperitoneal injection of STZ solution,the blood glucose of rats in group DM,H and L were greater than 16.7mmol/L,and the difference was statistically significant compared with NC group(P<0.01).At week 2,compared with DM group,there was no statistical significance in group H and L(P> 0.05).In the 4th and 6th weeks,compared with DM group,the blood glucose changes in H group were statistically significant(P<0.05).At week 8,compared with DM group,the difference in blood glucose between group H and L was statistically significant(P<0.05).4.Morris water maze test results Results of escape latency: on day 1,compared with NC group,the escape latency of rats in DM group was statistically significant(P<0.05).On day 2,compared with NC group,the results of group DM,H and L were statistically significant(P<0.01),and the results of H group and DM group were statistically significant(P<0.05).On day 3,compared with NC group,the results of group DM,H and L were statistically significant(P<0.01?0.05).Compared with DM group,the results of group H and L were statistically significant(P<0.01?0.05).On day 4,compared with NC group,the results of group DM,H and L were statistically significant(P<0.01).Compared with DM group,the results of group H and L were statistically significant(P<0.01).The results of the first crossing platform time: the first crossing platform time of NC group was the least,and the results of group DM,H and L were statistically significant(P<0.01).Compared with DM group,the difference between group H and L was statistically significant(P<0.01?0.05).The number of crossing the platform results: the results of the four groups were different,but the difference was not statistically significant(P>0.05).5.HE staining results of rat hippocampal tissue: the hippocampal CA1 region structure of rats in each group was observed under a microscope.It can be seen that the neuronal cells in NC group were relatively complete in structure,full in shape,closely and evenly arranged,and the number of cells was more than that in other groups.The nucleus was large and round,showing blue or light blue,and the nucleolus was clear.The structure of neurons in DM group was disordered,the arrangement was scattered,the number of neurons was reduced,the morphology was different,and the nuclei were pyknosis and stained deeper.Compared with the model group,the number of neurons in group H and L was more,arranged closely and the morphology was normal.6.The results of neurotransmitter quantitative analysis based on LCMS:Methodological validation results meet the requirements of biological sample determination.Multivariate statistical analysis results: the principal component analysis(PCA),partial least squares discriminant analysis(PLS-DA)and orthogonal partial least squares discriminant analysis(OPLS-DA)scores of NC group and DM group showed that the trend of hippocampal tissue samples in NC group and DM group was obvious,and there was no fitting,indicating that the metabolism of hippocampal tissue in DM group rats induced by STZ had changed,and the model was successfully established.The results of PCA,PLS-DA and OPLS-DA scores in group H and L were compared with those in DM group,respectively.The results showed that the scores of PCA,PLS-DA and OPLS-DA were significantly separated,and no fitting occurred,indicating that Yiqi Bushen Recipe had a certain protective effect on rats with memory cognitive impairment.Univariate analysis results: compared with DM group,there were significant differences in the metabolism of three neurotransmitters in the hippocampus of rats in H group(FDR<0.05).The expressions of DOPA and 5-HTP were up-regulated,and the expression of NE was downregulated.The metabolic differences of two neurotransmitters in L group were statistically significant(FDR<0.05),in which the expression of DOPA was up-regulated and that of NE was down-regulated.Conclusion:1.Yiqi Bushen Recipe can improve the general condition of STZ-induced diabetic rats,improve the pathological damage of brain tissue,and improve the memory and cognitive ability of rats.2.Yiqi Bushen Recipe can regulate the metabolism of neurotransmitters in hippocampus of diabetic rats,mainly by down-regulating the expression of NE and up-regulating the expression of DOPA and 5-HTP. |
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