ABSTRACT
<p><b>OBJECTIVE</b>To screen for the optimal dose of benzene and cyclophosphamide using an orthogonal design for establishment of New Zealand rabbit models of aplastic anemia.</p><p><b>METHODS</b>Following an orthogonal experimental design, the effects of 3 levels of 4 factors, namely the dose of benzene (A), the dose of cyclophosphamide (B), the number of benzene injections (C), and the number of cyclophosphamide injections (D) were tested in the establishment of New Zealand rabbit models of aplastic anemia using a L(3) orthogonal table, and the optimal protocol for the model establishment was selected from the 9 experimental groups. Each rabbit received subcutaneous injection of benzene on the back every other day, followed by daily cyclophosphamide injection via the ear vein for prescribed times. The blood routine was examined every 6 days, and before modeling and at 36 days after modeling, a small sample of the femoral bone was collected for bone marrow histopathological examination.</p><p><b>RESULTS</b>Comparison of the white blood cell, erythrocyte and platelet counts among the 9 groups showed successful modeling in Groups 4-9, and daily mean reduction rates of the cell counts in Groups 7, 8, and 9 differed significantly from those in the other groups (P<0.05). In Group 7, bone marrow sections showed low myelodysplasia, reduced hematopoietic tissue, reduced or even absence of megakaryocytes, and increased fat cells. Further observation found that the rabbits in Group 7 had sustained bone marrow suppression, consistent with the clinical characteristics of the disease.</p><p><b>CONCLUSION</b>Stable models of aplastic anemia can be established efficiently in New Zealand rabbits by a combination of 8 subcutaneous injections of benzene at 1.5 mL/kg and 4 intravenous injections of cyclophosphamide at 10 mg/kg.</p>
ABSTRACT
<p><b>OBJECTIVE</b>To study the effect of Tongxinluo superfine (TXL) on experimental anginal model induced by Arginine Vasopressin in rats with endothelial dysfunction.</p><p><b>METHOD</b>First, the endothelial dysfunction rat model was made by methionine-induced hyperhomocysteinemia (HHcy). The thoracic aorta were excised, and acetylcholine (Ach)-induced endothelium dependent relaxation and sodium nitroprusside (SNP) induced endothelium-independent relaxation were measured. Total plasma homocysteine (Hcy) concentrations were measured with automated fluorescence polarization immunoassay (FPIA). Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma von Willebrand factor (vWF) level. Plasma nitric oxide (NO) contents were assayed by method of nitrate reductase. Then, the rat model of collaterals contraction (model group) was established by AVP intravenous injection in rats with endothelial dysfunction and the S wave change (DeltaS) and T wave depression in Lead II ECG were used as the index of angina severity. The nitric oxide (NO) contents in serum and the expression of myocardium eNOS mRNA were measured.</p><p><b>RESULT</b>Ach (0. 1-1000 nmol L(-1))-induced endothelium dependent relaxation (EDR) of aortic rings was significantly decreased in HHcy group. The endothelium-independent relaxation induced by SNP (0.001-10 micromol L(-1)) was not significantly different between the two groups. Plasma homocysteine concentrations and vWF levels in rats treated with methionine were higher than those of control group, while NO contents were significantly decreased in HHcy group compared with control. The results showed that L-methionine intake induced hyperhomocysteinemia in rats. Impaired EDR, increased vWF and decreased NO suggested the exist of endothelial dysfunction. DeltaS of model group increased from 1 min to 5 min and T wave of model group depressed at 2 min compared with that of control after the administration of vasopressin (0.5 U kg(-1)). The intragastric administration of TXL inhibited vasopressin-induced S wave change at 4 min and 5 min and T wave depression from 30 s to 3 min after AVP injection. The NO contents in serum and the expression of myocardium eNOS mRNA of TXL group were increased compared with model group.</p><p><b>CONCLUSION</b>Experimental angina induced by AVP injection is more severe in rats with endothelial dysfunction. Tongxinluo Superfine can protect against collaterals contraction in rats maybe by increasing the NO contents in serum and the expression of myocardium eNOS mRNA.</p>