ABSTRACT
The aim of this study is to explore the tissue distribution of PEGylated puerarin in acute myocardial ischemia model rats. Healthy male SD rats were randomly divided into two groups (30 each). Both were given PEGylated puerarin at a dose of 488 mg x kg(-1). After 5 min of medication, one group was normal rats, another group with acute myocardial ischemia was established by peritoneal injection of 50 mg x kg(-1) isoprenaline. After administration, the animals were executed at 30, 60, 90, 120, 150 and 180 min, then heart, liver, spleen, lung, kidney were extracted. The content of puerarin in organ tissue was determined by HPLC. The results showed that the AUC of tissue distribution of PEGylated puerarin in normal rats was liver > kidney > heart ≈ spleen > lung > brain. While the AUC of tissue distribution of PEGylated puerarin in acute myocardial ischemia model rats was liver ≈ heart > kidney > lung ≈ spleen > brain. AUC(heart) of PEGylated puerarin in acute myocardial ischemia model rats was 1.7 times than that of the normal rats, and there was significant difference (P < 0.05). Thus, PEGylated puerarin had a good heart-targeting property in early myocardial infarction area, drugs could accumulate in the ischemic myocardium. It provided important information for further study and clinic use of PEGylated puerarin.
ABSTRACT
Objective To explore the effects of maternal hypercholanemia on the myocardium changes in rat fetus. Methods Thirty clean SD female rats were equally randomized to three groups after mating successfully.From the 13th to 20th day of gestation,group A and B were injected injected with sodium chloride(NS) as control.Total bile acid(TBA) and cardiac troponin I(cTnI) were measured in the maternal and fetal serum on the 21st day when all rats were killed.Fetal cardiac muscle cells were also collected for examination with light microscope and electronic microscope.Results (1)TBA in maternal and fetal serum were(22.32±8.12)μmol/L and(28.84±8.06) μmol/L,respectively in group A,(9.77±3.56)/μmol/L and(9.34±3.54) μmol/L in group B,and (3.60±1.78) μmol/L and(3.95±1.19) μmol/L in group C.Significant differences were found among groups(P<0.01).(2)Fetal death rates were significantly different among the three groups (P<0.05),with 30.11%,16.85%,and 7.05%,respectively.(3)Fetal cTnl were also found significant difference among groups(P<0.01),with(19.98±7.75)ng/ml,(11.41±3.64)ng/ml and(4.38±1.19)ng/ml,respectively.(4)The integrated scores of fetal necrosis area were significantly different in three groups(P<0.05),with 1.92±0.43,1.36±0.37 and 0.44±0.12,respectively.(5)Under electronic microscope,the number density of mitochondria in group A was lower than that in group C(P<0.05)while the average volume of mitochondria was larger in group A (P<0.05).The average volume of mitoehondria in group B was larger than that in group C(P<0.05) while no difference was found with regard to the number density between the two groups.The number density and average volume of myofibril in group A were lower than those in group C(P<0.05).The number density of myofibril in group B was higher than that in group C(P<0.05) while no difference was found with the average volume.(6)Positive correlations were found in maternal TBA,fetal TBA,fetal cTnI and the integrate of fetal necrosis area when comparing every two of the above factors. Conclusions Fetal myocardium is impaired obviously in hypercholanemia rats.The serum level of TBA and cTnI in fetal rats are positively correlated with each other.