Dilated Cardiomyopathy Ask1 Expression And Effects Of Astragalus

ObjectiveA DCM (dilated cardiomyopathy) rats model was set up by adrimycin intraperitoneal injection, which was used to analysis the expression of ASK1 (Apoptosis signal-regulating kinase 1,ASK1) and the effect of ASK1 on DCM start and development; analyze the relationship between the changes of ASK1 expression and heart function. And do research on astragalus effect on the expression of ASK 1.Metheds120 Wistar rats were randomly assigned into two groups:normal group (n=15) and DCM group (n=105). Adriamycin was diluted to lmg/ml with nomal saline, and then injected into model group rats with 2.5mg/kg/times in way of abdominal cavity; while, the rats in normal group were injected nomal saline with the same quantity and in the same way. Both groups were injected 3 times in the first week, another 3 times in the forth week, total 6 times. Then, the DCM rats model induced by adriamycin was set up.(2) At the end of 8th week,47 DCM rats were selected and divided into two groups randomly:DCM model group (n=27) and the astragus group (n=20). Meanwhile, the left 10 rats in the normal group were observed continuously. Did drug interference to the three groups as following:fill the stomach with 2ml double distilled water and astragalus grain of 12g/kg/d in the asragus group; fill the stomach with 2ml doubl distilled water in both 12-week DCM model group and the normal group(n=10). The four groups had intragastric administration once per day and continued 4 weeks.(3) Examine the LVEF(the average value of three continue complete cardiac cycles) of all the live rats. Left ventricle of rats died at the 8th week and 12th week were stayed behind for ASK1 Western-blot examination.Result(1) At the very beginning of adriamycin injection, the model group rats appeared lack of movement,thin,eat less,diarrhea,slow reaction, and gradually exacerbated. At the end of 8th week, the rats became thin evidently, and part of them shown abdominal bulging, hair removal, and hair color less smooth.(2)Pathology results:At the end of 8th week, the rats'heart in model group became large significantly. HE colaration shown that, myocardial fibers arranged disorderly and appeared rupture. Cell clearance became wider; cardiac muscle cell swelled and dropsy occurred;and myocardial cell vacuoles degeneration was happened.(3) Heart ultrasound shown that, LVDD&LVSD increased and LVEF decresed when compared with the rats in normal group, and the differences are statistically significant (P< 0.01).2 ASKl expression changement of myocardial DCM:Myocardial ASKl exresssion in normal group rats shown a low level, and was much lower than 8 weeks model group rats. The difference between the two groups are statistically significant (P< 0.01).The ASKl Western-blot number expression in 12 weeks model rats was less than 8 weeks model rats, which means ASKl expression will show more significant with the longer duration, and the difference between the two groups is statistically significant (P< 0.01).3 ASKl expression in myocardial DCM with astragalusASKl expression in 12 weeks astragalus group rats was lower than 12 weeks model group rats and higher than normal group rats, and the differences are statistically significant (P< 0.01), which means astragalus can decrease DCM rats cardiac ASKl expression.4 Cardiac function comparision after 12 weeks:At the end of 12 weeks, astragalus model group's LVEF was higher than model group but lower than normal group, the difference is statistically significant (P< 0.01). That means after treatment, heart funciton have been improved, but still failed to return to a normal level.5 Cardiac function compansion before and after the treatment:The LVEF in 12 weeks model group rats was lower than that in 8 weeks model rats, and the difference is statistically significant (P< 0.05). The LVEF in 12 weeks astragalus group rats is higher than that in 8 weeks, and the difference is statistically significant (P< 0.05). It is shown that, DCM rats cardiac function will become lower and lower with the increasing of duration time, however astragalus can improve DCM rat cardiac function.6 ASK1 expression quatity in DCM rats shows negtively relaiton with LVEF, and r is-0.87, P< 0,01.Conclusions1. Normal rats'myocardia have ASK1 expression with a low level.2. DCM rats will have more ASK1, and ASK1 will increase insignificantly with the longer duration.3. ASK1 expression in DCM rats shows negatively relation with the changement of LVEF.4. Astragalus can lower ASK1 expression in DCM rats, and can improve cardiac function effectively.