Effects And Mechanism Of Shujin Jiannao Recipe On Cognitive Function In Patients With Cerebral Palsy

1 Objective1.1 Literature research:To explore the medication rules of traditional Chinese medicine in the literature for the treatment of cerebral palsy,so as to provide the basis for clinical medication of traditional Chinese medicine.1.2 Pharmacological research:Network pharmacology was used to explore the mech-anism of Yizhiren in the treatment of CP and the possible mechanism of improving the cognitive function of CP.1.3 Clinical study:To observe the clinical efficacy of shujinjiannao formula combined with selective posterior rhizotomy(SPR)in the treatment of patients with spastic cerebral palsy,so as to provide clinical basis for traditional Chinese medicine to improve the rehabilitation of patients with spastic cerebral palsy.1.4 Basic research:Based on Bcl-2/Bax and Caspase-3,the mechanism of shujin-jiannao Decoction in improving cognitive function of hypoxic-ischemic brain injury was studied.2 Methods2.1 Literature research:Literatures on cerebral palsy treated with traditional Chinese medicine were retrieved from CNKI,Wanfang,VIP,PubMed,web of science and CO chrane library databases.Excel table was used to analyze the medication methods,frequency,four Qi and five flavors and meridian tropism;SPSS modeler 18.0 software was used to analyze the prescription rules,SPSS statistics 24 was used to analyze the factor analysis and cluster analysis.2.2 Pharmacological research:The active ingredients and targets of Alpinia oxyphylla were obtained and screened through tcmsp,and the main targets of CP were obtained through gencards,OMIM,TTD and drugbank Cytoscape 3.7.2 software was used to construct the intersection network of active components and targets of Alpinia oxyphylla.The PPI network was constructed by using string platform to obtain the key active components and core protein targets.The go analysis and KEGG pathway enrichment analysis of the common targets were carried out through the micro information network.2.3 Clinical study:A prospective,single center,randomized controlled clinical trial was conducted.The patients were randomly divided into the experimental group and the control group.Both groups were given SPR operation and rehabilitation training.The experimental group was given Shujin Jiannao granule orally for 2 months after operation.General information,Chinese Binet test score,gmfm-88 score,CSI score,ADL score,muscle strength,muscle tension and body mass scale scores of patients and their mothers were collected.2.4 Basic research:7-day SD rats were divided into 6 groups:control group,model group,minocycline group,low,medium and high-dose shujinjiannaofang groups.The cerebral palsy model of hypoxic-ischemic brain injury was established by rice vannucci model.Weighing,behavioral test and he staining were given after operation.Then the control group and model group were given the same amount of normal saline by gavage.The drug group was given the corresponding drug by gavage for 1 week,The expression of Bcl-2,Bax and Caspase-3 in hippocampal CA1 area was detected by immunohistochemistry.The expression of Bcl-2,Bax and Caspase-3 in hippocampus was detected by WB.3 Result:3.1 Literature research:The top six drug frequency:Angelica sinensis,Shenjincao,Achyranthes bidentata,Astragalus membranaceus,safflower and Paeonia lactiflora.The drug is warm in nature,sweet,pungent and bitter in taste,and belongs to liver,kidney and spleen meridians.Correlation analysis showed that the core drugs were Tougucao,Achyranthes bidentata and Shenjincao.Six common factors were extracted.Cluster analysis included Angelica sinensis,Ligusticum chuanxiong,Glycyrrhiza uralensis,astragalus,eucommia,Salvia miltiorrhiza,Ramulus Cinnamomi,safflower,Paeonia lactiflora,Achyranthes bidentata,papaya,Tougu grass,Spatholobus Spatholobus,extensor grass.3.2 Pharmacological research:A total of 8 active components were screened out,the key active components were oleic acid,daucosterol,?-sitosterol,etc.,18 targets of Alpinia oxyphylla on CP,TP53,Myc,CASP3,CASP8,ALB,etc.as the core targets of PPI network,84 go entries and 292 KEGG pathways were enriched(P<0.05),mainly in cancer signaling pathway.3.3 Clinical study:(1)There was no abnormality in the baseline of the two groups,mainly male,aged between 5-13 years old,most of them were spontaneous delivery of the first fetus,mixed feeding,and most of the spastic cerebral palsy patients were diplegia.(2)After treatment,the IQ score of the experimental group was higher than that of the control group(P=0.002<0.05),and it was significantly higher than that before treatment(P<0.05).(3)In the gmfm-88 score,the exercise score of the experimental group was higher than that of the control group after treatment,and the function of C,D and e areas was improved significantly(P<0.05).Within group comparison,except for the gmfm-a area of the control group(P=0.094>0.05),the motor function scores of the other four areas and the five areas of the experimental group were significantly improved(P<0.05).(4)CSI score,ADL group showed significant improvement(P<0.05).(5)Muscle strength statistics,after treatment,the iliopsoas muscle,biceps femoris muscle and posterior tibialis muscle in the experi-mental group were better than those in the control group(P<0.05);intra group comparison,the muscle strength of iliopsoas muscle,quadriceps femoris muscle and biceps femoris muscle in the experimental group and the control group were better than those before treatment(P<0.05).(6)The muscle tension of the experimental group and the control group were improved after treatment(P<0.05).(7)In the constitution,the experimental group had Qi deficiency and yin deficiency before treatment,while the control group had Qi deficiency before and after treatment.Yin deficiency and phlegm dampness were common in mothers.3.4 Basic research:(1)Body weight:after one week of intragastric administration,the body weight of the two groups were significantly improved(F=11.799,P=0.000<0.05).The body weight of the middle dose and high dose groups was significantly better than that of the model group(P<0.05).(2)Behavior:there were significant differences between the two groups(P<0.05).One week after intragastric admini-stration,the suspension time of minocycline group,medium dose group and high dose group was longer than that of model group(P<0.05).The middle dose group and high dose group shortened the tilt time(P<0.05).All the treatment groups could improve the neurological function(P<0.05).(3)HE staining:The neurons in CA1 area of hippocampus in the control group were abundant and arranged as a whole,and the cell structure was clear.In the model group,the number of nerve cells decreased,the cell shape was irregular,the cytoplasm decreased,and the nucleus became smaller or disappeared.(4)The expression of Bax and Caspase-3 in CA 1 area of hippocampus was significantly decreased in minocycline and low-dose Chinese medicine groups(P<0.05).The expression of Bcl-2 was increased in middle and high-dose Chinese medicine groups(P<0.05),and the expression of Bax and caspase-3 was decreased(P<0.05).(5)WB test statistical analysis:The high dose group of traditional Chinese medicine promoted the expression of Bcl-2,while minocycline group and low,medium and high dose of traditional Chinese medicine could reduce the content of Bax protein(P<0.05).The ratio of Bcl-2/Bax was increased by drug treatment(P<0.05),and it was proportional to the dose of traditional Chinese medicine.The expression of caspase-3 protein was inversely proportional to the dosage of traditional Chinese medicine.Only high dosage of traditional Chinese medicine significantly reduced the expression of caspase-3 protein(P<0.05).4 Conclusion4.1 Literature research:In the treatment of cerebral palsy patients,strengthening healthy qi and eliminating pathogenic factors are used together,tonifying liver,spleen and kidney,supporting healthy qi,expelling wind,activating blood circulation,dredging collaterals and removing pathogenic factors,and attaching importance to supporting healthy qi drugs.4.2 Pharmacological research:This study preliminarily revealed the mechanism of action of multi-component,multi-target and multi-channel of Alpinia oxyphylla.Bcl-2,Bax and caspase-3 are the main gene proteins of apoptosis,which is the focus of basic experimental research.4.3 Clinical research:Traditional Chinese medicine can help improve the motor func-tion and cogniti ve function of patients with spastic cerebral palsy after operation.It has a certain influence on the improvement of physical fitness in patients with spastic cerebral palsy.4.4 Basic research:The synergistic effect of shujinjiannao formula can protect hippocampal neurons and reduce apoptosis by increasing the ratio of Bcl-2/Bax and reducing the protein expression of Caspase-3 in the brain injury caused by ischemia and hypoxia,and it is positively correlated with the dose of the drug.