Experimental Study On Prevention And Treatment Of Early Atherosclerosis By Spleen Prescription From 5 - HT And Its Receptor In Hypothalamus

Purpose:The aim of the test is to investigate the intercention mechanism of early onset of atherosclercsis by the mesn of regulating effect of Jianpifang prescription on the Apoe-/- mice’s hypothalamic serotonin(5-HT).Material and method:Thirty 9-week-old male Apo E-/- mice are randomly divided into 3 groups: the model group、the atorvastatin group(hereinafter referred to as the western medicine group) and the Jianpifang prescription group. Another twenty male C57BL/6N mice from same strain are divided into the normal group and the Danchunyaowuganyu group( GY group or the pure drug intervention group) to help observe and compare. The mice of the normal group are fed with common feedstuff,while the mice from the GY group, the model group, the western medicine group, as well as the Jianpifang prescription group are all given high-fat-feedstuff. Meanwhile, the ones of the normal group and the model group are given normal saline through gavage, the ones of the GY group are given the dose of Jianpifang prescription through gavage, the mice of the western medicine group and the Jianpifang prescription group are given the corresponding drugs and different dose through gavage. After a week of adaptive feeding and then 12-week continuous gavage, all mice are weighted every Monday every week and their food consumption of the mice are measured every 10 days. From the thirteenth week, the mice ’s hypothalamus morphologic changes, body weight among the different groups, hypothalamus serotonin(5-HT) and 5-hydroxy indole acetic acid(5-HIAA) content and the expression of serotonin receptor 2A(5-HT2AR), as well as serotonin receptor 2C(5-HT2CR) start to be observed.Results:1.The mice’s remaining feedingstuff on the eleventh week shows that, comparedwith the normal group, the model group’s remaining feedingstuff volume increases(P<0.05); and by the comparison with the model group, the mice’s feedingstuff volume in each group reduces(P<0.05), and the remaining amount of the Jianpifang prescription group is less than the one of the western medicine group(P<0.05), nearly close to the one of the normal group(P>0.05).2. The mice’s body weight in each group significantly increases at the end of the 13 th week. Compared to the weight gain of the model group, the one of the model group slows down(P<0.05); by the comparison with the weight of the model group, the mice’s weight from each group increases(P<0.05)and the mice’s weight of the Jianpifang prescription group is heaver than the one of the western medicine group(P<0.05), close to the one of the normal group(P>0.05).3. Under the HE straining microscope through the aortic morphological comparison, the form and structure of the normal group’s neurons is visible and complete, with clear cytoplasm, round or oval nuclei, clear nuclear membrane, much chromatin, and obvious nucleolus, without inflammatory cell infiltration. The number of neurons of the model group decreases, with some of the neuron cell structures disappearing, the cytoplasm unclear, lack nucleoli, gathering a large number of infiltrating inflammatory cells, lymphocytes, monocytes and neutrophils.The GY group and Jianpifang group: their form and structure of the neurons in this group recover well, with the clear cytoplasms and nucleoluses, and visible scattered small lymphocytes, monocytes and neutrophils.The western medicine group: the number of neurons increases. The form and structure of the neurons in this group recover well. This group is accompanied with some of the clear cytoplasm and nucleolus, and visible scattered lymphocytes, monocytes and neutrophils.4. Under the HE straining microscope through the hypothalamus morphological comparison, the form and structure of the normal group’s neurons is visible and complete, with clear cytoplasm, round or oval nuclei, clear nuclearmembrane, much chromatin, and obvious nucleolus, without inflammatory cell infiltration. The number of neurons of the model group decreases, with some of the neuron cell structures disappearing, the cytoplasm unclear, lack nucleoli, gathering a large number of infiltrating inflammatory cells, lymphocytes, monocytes and neutrophils.The GY group and Jianpifang group: their form and structure of the neurons in this group recover well, with the clear cytoplasms and nucleoluses, and visible scattered small lymphocytes, monocytes and neutrophils.The western medicine group: the number of neurons increases. The form and structure of the neurons in this group recover well. This group is accompanied with some of the clear cytoplasm and nucleolus, and visible scattered lymphocytes, monocytes and neutrophils.5. It shows, through the contents check about hypothalamus 5-HT and 5-HIAA, by comparison with the contents of 5-HT and 5-HIAA of the normal group, the ones of the model group decrease(P<0.05), by comparison with the ones of the model group, the contents of the mice’s hypothalamus 5-HT and 5-HIAA, from the treatment groups increase(P<0.05), thereinto the Jianpifang group is superior to the GY group(P<0.05) and close to the normal group(P>0.05). 6. The results of 5-HT2 AR, 5- HT2 CR of the grey values in the mice’s hypothalamus tissues show that, the grey values is inversely proportional to the positive expression, that is to say, the positive staining is the deeper, the lower the grey value is. By comparison with the positive expression of the normal group, the one of the model group significantly raises(P<0.01); by comparison with the one of the model group, the positive expression of other treatment groups decreases(P<0.01); the positive expression of the Jianpifang group is superior to the one of the western medicine group(P<0.01) and close to the one of the GY group(P>0.05).Conclusion:1. Change in body weight and food intake in Aop E-/- mice is due to long-termhigh-fat diet-induced with cause spleen fails2. The mechanism of Jianpifang intervention to the early atherosclerosis is related to the regulation of inflammatory cells’ gathering.3. The mechanism of Jianpifang intervention to the early atherosclerosis is related to the regulation of the hypothalamus 5-HT and 5-HIAA.4. The mechanism of Jianpifang intervention to the early atherosclerosis is related to the regulation of the hypothalamus 5-HT2 AR and 5-HT2 CR.