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Study Of ShenQi Prescription That Affect Vascular HO-1, P38MAPk And PGC-1mRNA Of GK Rats

Posted on:2013-04-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z X YueFull Text:PDF
GTID:1224330395955979Subject:Chinese medical science
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Purpose:Through testing the level of MDA, H2O2and SOD、CAT, observing the pathological changes of abdominal aorta after HE staining, the ultra fine structure and mitochondrion of the cell of abdominal aorta under transmission electron microscope, the expression of HO-1、P38MAPK by SABC way, and the expression of PGC-1mRNA by RT-PCR way, this topic tests the effect of Shenqi Compound Recipe on vascular tissue and Oxidation and antioxidation system of Diabetic macrovascular disease model rats from overall and cell level, for dicussing the mechnism of Shenqi Compound Recipe in preventing Diabetic macrovascular disease, further providing therapy basis on TCM. preventing Diabetic macrovascular disease.Method:The55GK rats that RBG>11.0mmol/L are randomly divided to Blank group (14)、 Model group(13)、Atorvastatin group(14)、Shenqi Compound Recipe group(14).14Normal Wistar rats are set as controll group. We manufacture model by let GK rats of Model group、Atorvastatin group、Shenqi Compound Recipe group drining water containing0.1mg/ml L-NAME.At the same time, The controll group、Blank group anc Model group are administered Physiological saline by5mg/kg. d; Atorvastatin group are administered Atorvastatin by1.6mg/kg. d(being5times dose of that of adults); the Shenqi Compound Recipe are administered Shenqi Compound Recipe suspension b、1.44g/kg. d (being10times dose of that of adults). The period is35days, and at the same time, the Wistar group are fed on common diet, the GK rats are fed or high fat diet.We measure the weight of rats once a week, record the mentality、 dringking、diet、activities、fur gloss. Then we killed the rats, measuring the level of MDA、H2O2、SOD、CAT of blood from Femoral artery by RIA way, observing pathological changes after HE staining and the changes of the ultra fine structure of abdominal aortic under transmission election microscope, the expression of HO-1、 P38MAPK by SABC way, and the expression of PGC-1mRNA by RT-PCR way. Results:The mentalities and activities of Shenqi Compound Recipe group are better than that of model group; Wistar group eat more than GK groups(P<0.01). During experiment, the feeding amount of Shenqi Compound Recipe group is more than that of other GK groups from the5th week(P<0.01), while that of oher GK groups has little changes. The Wistar group drink less than the GK goups(P<0.01). During the experiment, the amount of the Wistar group and Shenqi Compound Recipe group drink increase less than other groups (P<0.01).The weight of all groups increase, that of the Wistar group increase more than that of others(P<0.01), While that of the model group slowest, and at the end of experiment, the weight of Shenqi Compound Recipe group more than the model group(P<0.01).The level of MDA of model group is higher than other GK groups(P<0.05), while there is no significant difference between Shenqi Compound Recipe and Atorvastatin group (P>0.05). The activity of SOD of model group is lower than other GK groups, but there is no statistical significance, that of Shenqi Compound Recipe and Atorvastatin groups higher than model group(P<0.01) while that between Shenqi Compound Recipe and Atorvastatin groups has no significant difference (P>0.05). The level of CAT is lower than other GK groups(P<0.01), that of Shenqi Compound Recipe and Atorvastatin group higher than that of model group(P<0.01), whlie that of Shenqi Compound Recipe higher than that of Atorvastatin group(P<0.05). The level of H2O2of moedl group is higher than GK groups, but there is no statistical significance between them(P>0.05), that of Shenqi Compound Recipe group lower than that of model group(P<0.05), and that of Atorvastatin group lower than that of model group, but no statistical significance(P>0.05). The expression of HO-1of model group is lower than that of GK rats(P<0.01). that of Shenqi Compound Recipe higher than that of model group(P<0.01), while there being no significant difference between the Atorvastatin group and the model group(P>0.05).The expression of p38MAPK is significant higher than that of other groups and that of Shenqi Compound Recipe and Atorvastatin group is lower than that of model group, while there is no significant difference between the two groups (P>0.05). The expression of PGC-1mRNA is lower than other GK groups, that of Shenqi Compound Recipe lower than that of model group (P<0.05), while that between Atorvastatin group and the model group not statistical significant(P>0.05). Through light microscope observation, the vascular intima of model group thicken, and thers is more foam cell and fibrous tissue hyperplasia and atherosclerotic changes. The changes of Shenqi Compound Recipe and Atorvastatin group is less than other GK groups, through electronic microscope observation, compared with GK rats, the structure of endothelial cells is unclear or the membrances rupture, subendothelial layer thickens, smooth muscle cell vacuolarly degenerate, collagen fiber membrance incraese, mitochodrion reduce, the ultrastructure lesions of arterial endothelial cell of Shenqi Compound Recipe and Atorvastatin groups is slighter and the mitochondrial structure is clear.Conclusion:L-NAME combined with high fat diet can diabetic macroangiopathy animal model by GK rats. Shenqi Compound Recipe can improve the mentalities, relieve the symptoms of dringking more, improve the ability to clear oxygen free radicals of diabetic macrovascular rats, inhibit oxidative stress injury, can correct the oxidant/antioxidant imbalance, increase vascular endothelial cell mitochondria synthesis, retard and prevent diabetic macrovascular disease. The mechanism may be improving the antioxidant enzymes, reducing oxygen free radicals, increasing the level of HO-1, inhibitting the p38MAPK protein activation, increasing vascular PGC-1mRNA expression and mitochondrial biogenesis in vascular cells.
Keywords/Search Tags:Shenqi Compound Recipe, diabetic macrovascular disease, oxidative stress, atherosclerosis, T.C.M.
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