The Research Of Theory And Experiment On Treating Inflammatory Factors Of Vascular Atherosclerosis With The Method Of Xiaoxianxiongtang

Objectives: Applying the tradional Chinese medical method of Xiaoxianxiongtang treating the atherosclerosis, to explore the dynamic change of Phlegm-stasis in the rat atherosclerotic model as the time goes on. Through observing the effect of protect the vascular of the atherosclerosis (AS) rats model, the morphological changes of aortic endomembrane, the effect of the blood lipids, the changes of hemorrheologic parameters and the morphological inflammatory factors, to illuminate the correlation between"Chinese medicine Phlegm-stasis disease"and"inflammatory factors and control mechanisms", and prove the scientific value of Xiaoxianxiongtang.Method:Theory exploring: On the basis of collecting the correlative articles of past dynasties and of present age, this article investigated the pathogenesis of traditional Chinese medicine on the atherosclerosis. Indicating that"Phlegm-stasis"was the invading foundation of AS,"fluids cohered and phlegm collected","obstruction of collaterals"were main pathological sectors, and"masses developed with Phlegm-stasis"was the main patho-changes. It also established the treatment of"resolving blood stasis and expelling phlegm, expelling masses to dredge collaterals"and formulated Xiaoxianxiongtang with it.Experimental research:Effect of Xiaoxianxiongtang on renal protection in AS: the AS model established by fat meal and once intraperitoneal injection of Vd3. The male SD rats were randomly divided into 4 groups: blank control group, model group, and simvastatin group, Xiaoxianxiong group. The blank control group was fed with common feedstuff, and the other groups were fed with high fat feedstuff. The simvastatin group and Xiaoxianxiong group were given suspension of simvastatin and Xiaoxianxiongtang separately by intragastric administration on the basis of high fat diet. The blank control group and model group were given equal volume of menstruum. All the groups were fed with medicine 8 weeks continuously except normal group.Eight weeks later, blood was taken to test the blood lipids [total cholesterol (TC) and at same time triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C)] and the hemorheology were investigated. Meanwhile, blood was taken to be detected the morphological inflammatory factors [inter-cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)] by immune histological chemistry and hs-CRP was detected by ELISA, and the expression of ICAM-1, VCAM-1mRNA in the aortic tissue of 8 weeks'animals were examined by reverse transcription polymerase chain reaction (RT-PCR).Results:1 The effect of Xiaoxianxiongtang on blood lipids, the hemorheology and the morphological changes of aortic endomembrance of atherosclerosis rats: compared with the blank control group, the contents of TC, TG, LDL-C of model group of each period were all increased significantly(P<0.01), HDL-C was decreased significantly(P<0.01); compared with the model group, the contents of TC, TG, HDL-C, LDL-C of simvastatin group of each period were all decreased significantly(P<0.01). compared with the model group, the contents of TC, TG, HDL-C,LDL-C of Xiaoxianxiongtang group of each period were all decreased significantly(P<0.01); compared with the simvastatin group, the contents of TC, TG, HDL-C, LDL-C of Xiaoxianxiong group was no significant difference(P>0.05).Compared with the blank control group, the contents of hemorheology of model group of each period were all increased significantly(P<0.01); compared with the model group, the contents of hemorheology of Xiaoxianxiongtang group of each period were all decreased significantly(P<0.01); compared with the model group, the contents of hemorheology of simvastatin group was of no significant difference(P>0.05). HE staining results:Model group: 8 weeks later, some matured plaques can be seen on the aortic tunica intima of model group, the plaques were composed by foam cells, fibroblast, smooth muscle cells, collagenous fibers, inflammatory cells and so on; the fibrous tissues proliferated significantly; fibrous layers can be seen on the surface of some plaques.Simvastatin group: 8 weeks later, the aortic tunica intima of model group thickened, the endothelial cells multiplied, the foam cells gathered and proliferated under the endothelial cells, the plaques changes were less serious than those of model group, the amounts of inflammatory cells decreased, and the pathological changes were ameliorated.Xiaoxianxiongtang group: 8 weeks later, the plaques of Xiaoxianxiongtang group decreased significantly and even disappeared, the amounts of foam cells were also decreased significantly, the endothelial cells multiplied, and slightly swelled, the pathological changes were significantly ameliorated.Electronic microscope results:Model group: 8 weeks later, the aortic endotheliocyte swelled, the granules on its rough surfaced endoplasmic reticulum significantly desquamated, the quantity of mitochondrion reduced and the cristae decreased, coalesced, even disappeared, the quantity of vesicles significantly reduced. Simvastatin group: 8 weeks later, the granules on the rough surfaced endoplasmic reticulum slightly broadened, the granules on its rough surfaced endoplasmic reticulum desquamated, the cristae of mitochondrion decreased, the quantity of vesicles reduced, the pathological changes were more ameliorated than those of model group.Xiaoxianxiongtang group: 8 weeks later, the granules on the rough surfaced endoplasmic reticulum obviously broadened with the shape of pool and slightly desquamated, the quantity of cristae comparatively increased, partly coalesced and disappeared, the pathological changes were significantly ameliorated.2 The effect of Xiaoxianxiongtang on the inflammatory factors expression of hs-CRP, ICAM-1, VCAM-1 of atherosclerosis rats: compared with the blank control group of each period, the intensity and scope of positive expression of hs-CRP, ICAM-1, VCAM-1 in aortic endothelial cells of model group were increased significantly(P<0.01); compared with the model group of each period, hs-CRP, ICAM-1, VCAM-1 expression of simvastatin group and Xiaoxianxiongtang group were significantly decreased(P<0.05, P<0.01); compared with simvastatin group, the intensity and scope of positive expression of hs-CRP, ICAM-1, VCAM-1 were decreased(P<0.01).3 The effect of Xiaoxianxiongtang on the expression of ICAM-1, VCAM-1 mRNA of aortic endotheliocyte of atherosclerosis rats: compared with the blank control group, the expression of ICAM-1, VCAM-1 mRNA of model group was significantly increased(P<0.01); compared with the model group, the expression of ICAM-1,VCAM-1 mRNA of simvastatin group and Xiaoxianxiong group was significantly decreased(P<0.05, P<0.01); the expression of ICAM-1, VCAM-1 mRNA of Xiaoxianxiong group was inferior to that of simvastatin group(P<0.01).Conclusions:1 On the basis of inflammatory changes of vascular atherosclerosis research, this subject investigated the traditional Chinese medicine pathogenesis and treatments of AS, it indicated the reason of the AS was"Phlegm-stasis collected". The experiment proved that AS was the result of"deficiency of collaterals","fluids cohered and phlegm collected"and"masses developed with obstruction of collaterals"were formed. There were internal correlations between"Phlegm-stasis collected"and"the composition and control mechanisms of inflammatory factors of vascular atherosclerosis". The treatments of"resolving blood stasis and expelling phlegm, expelling masses to dredge collaterals"were established, Xiaoxianxiong was formulated with it. These brought a new idea on theory.2 The study showed that Xiaoxianxiong had the effect of protecting the endothelium by improving the pathological changes of morphological of aortic end membrane and ultra microstructure of endothelial cells, it also had the effect of dropping fat and changing the masses of blood by decreasing TC, TG, LDL-C and decreasing the hemorheology, the protective effect of Xiaoxianxiong on endothelium function was supposed to be realized by dropping fat. 3 The study showed that Xiaoxianxiong can decrease the expression of ICAM-1, VCAM-1 mRNA of vascular atherosclerosis rats, reduce ICAM-1, VCAM-1 albuminoid expression, meanwhile it can decrease the expression of the inflammatory factors hs-CRP. Xiaoxianxiong's effects of all the above aspects were superior to simvastatin. This further proved that Xiaoxianxiong had long-term advantage in protecting endothelium and curing vascular atherosclerosis. Summing up the previous experiment, we may conclude that decreasing the expressing of inflammatory factors and gene may be one of Xiaoxianxiong's mechanisms of protecting endothelium. These could be explained that Xiaoxianxiong could repair the successive process of vascular endothelium disorders while decrease inflammatory factors, hemorheology and drop fat, and prove the scientific value of Xiaoxianxiong.