| Objective:Based on the results of previous studies of the Mongolian medicine Qiqirigan-8,and establish the Wistar rat model of Atherosclerosis,then by the RNA sequencing technology to search for the mechanism of Qiqirigan-8 mobilizes bone marrow vascular steam\progenitor cell to promote the repair of vascular endothelial injuryMethods:60 healthy male Wistar rats were randomly divided into blank group,model group,Qiqirigan-8 group A,Qiqirigan-8 group B,simvastatin group A,simvastatin group B,etc.There are 10 rats in each group.Rats in each group were given ordinary feed and drinking water and fed adaptively for 1 week.At the beginning of the experiment,all groups except the blank group were given high-fat feed,and unlimited diet.In the first week of the experiment,all groups except the blank group were given 700,000 units/kg X vitamin D3 injection of rat body weight(kg)by intraperitoneal injection,divided into three times and given every other day,finished within 1 week.Simultaneously with the modeling,the blank group(distilled water 2ml),model group(distilled water 2ml),Qiqirigan-8 group A(Qiqirigan-8 0.6g/kg)and simvastatin group A(simvastatin 2mg/kg)were given the corresponding drug suspension,once a day,at a specified time,continuous administration for 10 months.Starting from the 6th month of the experiment,the corresponding drug suspensions were given to the Qiqirigan-8 group B(Qiqirigan-8 0.6g/kg)and the simvastatin group B(simvastatin 2mg/kg).It is given once a day,at a specified time,for 5 consecutive months.During the experiment,the diet,mental state,the color and shape of urine and feces of each group were observed every day,and the weight was weighed at a fixed time every week.At the end of the 0th,4th,6th,and 10th months of the experiment,the rats in each group were drawn blood to examine the serum lipid content.At the end of the 10th month,the rats in each group were anesthetized,blood was collected and killed,and the femur,tibia and aorta were quickly separated.Quickly extract bone marrow cells from femur and tibia,and do RNA sequencing,analyze the results,use GO and KEGG gene library to find bone marrow vascular stem/progenitor cell mobilization related genes and signal pathways.The aorta was paraffin sectioned and stained with HE to observe its pathological changes.Results:1.The comparison results of the weight change of rats in each group showed that in the first 5 months,the weight gain of the blank group was fast,while the weight gain of the model group was slow,and the weight of the model group was significantly lighter than that of the blank group(P<0.05);In the last 5 months,the weight gain rate of the blank group rats was slow,while the weight gain rate of the model group was fast.The body weight of the model group was significantly higher than that of the blank group(P<0.05);There is no statistical difference between the weights of the rats in the treatment group and the positive control group compared with the model group,but there is a certain difference with the naked eye,especially in the last 4 months of the experiment.2.The final result of blood lipid testing showed that the content of TC and LDL-C in the model group was significantly higher than that in the blank group(P<0.05),and the content of HDL-C wassignificantly lower than that in the blank group(P<0.05);The TG content of the Qiqirigan-8 A group and Simvastatin B group was significantly lower than that of the model group(P<0.05),while the HDL-C content was significantly higher(P<0.05);Simvastatin A group had significantly lower levels of TG and LDL-C than the model group(P<0.05)。3.Pathological sections of the aorta showed that the intima structure of the model group was incomplete,with a large number of foam cells obviously gathered under the intima and protruding into the vascular lumen,and the smooth muscle cells of the middle membrane showed irregular hyperplasia,which proved the effectiveness of the model.The vascular intima in the blank group was smooth and flat,without foam cell aggregation and intima thickening.In other groups,the intima was rough and not smooth,which was significantly different from that of the model group.However,there was no obvious difference between the treatment group and the positive expectation.4.The results of mRNA sequencing and the analysis of GO,KEGG are showed that:(1)GO functional annotation analysis was carried out on the differentially expressed and co-expressed genomes of Qiqirigan-8,and the classification results of the two groups of genes were the same.The most of genes were concentrated in a subset such as metabolism,immune system process,adhesion,catalytic activity and stimulus response.Enrichment analysis of GO function showed the two groups of genes also focused on glucose metabolism,immune response,lipid metabolism,inflammation and other related GO functions.(2)The KEGG functional annotation results of the two groups of genes showed that in the subset,the annotation of glucose metabolism,immune response,lipid metabolism,inflammation and other related pathways is more obvious.The results of KEGG functional enrichment analysis of Qiqirigan-8 differential gene showed that the gene enrichment on MAPK,TNF,TLRs,CAMs,jak-stat,VEGF,PPAR,FoxO,TGF-receptor,EGFR,NF-κB et al metabolism pathwaysConclusion:1.Mongolian medicine Qiqirigan-8 has the effect of lowering blood fat and repairing atherosclerotic damaged vascular endothelium.2.The Mongolian medicine Qiqirigan-8 mobilizes Vascular steam\progenitor cell in the bone marrow through such signaling pathways as VEGF and TGF-β,thereby promoting the repair of vascular endothelial injury caused by atherosclerosis.3.Mongolian medicine Qiqirigan-8 may have potential effects on immune response,glucose metabolism,inflammation,etc.during the development of atherosclerosis.4.The Mongolian medicine compound preparations with the effects of warming the stomach,promoting turbid differentiation,promoting blood circulation and removing blood stasis,etc.,also have a certain effect on cardiovascular diseases. |
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