ABSTRACT
Objective Bevacizumab ( BM ) is an angiogenesis inhibitor widely used in cancer therapy, but its off-target effect of proteinuria may lead to discontinuation of treatment.This study was to explore the mechanisms of BM inducing proteinuria in mice. Methods Twenty-four healthy mice were randomly divided into four groups, saline control, low-dose BM, medium-dose BM, and high-dose BM, treated by injection of normal saline and BM at 10, 35, and 60 mg per kg of the body weight, respectively, though the tail vein.At 4 weeks after injection, 24-hour urine was collected to determine the total urine protein and blood obtained from the eyeballs for biochemical analysis.Then all the mice were sacrificed and the kidneys harvested for observation of pathologic changes in the glomeruli as well as for immunohistochemistry, Western blotting, and real-time PCR analysis. Results Compared with normal saline,BM obviously elevated the level of 24-hour urine protein, with statistically significant differences between the control and the medium-and high-dose BM groups (0.23 ±0.02 vs 1.14 ±0.13 and 1.43 ±0.10, P0.05).No significant differences were observed among the four groups in the levels of Cr, BUN, AST and ALT (P>0.05).Under the optical microscope, the kidneys showed normal structures in the control group, no signifi-cant pathologic changes in the low-dose BM, and vacuolus-like alteration with atrophic glomerular endothelial cells in the medium-and high-dose BM groups.Immunohistochemical analysis demonstrated the expressions of VEGF and podocin were moderately or strongly positive in the control and low-dose BM groups, by weakly positive or negative in the medium-and high-dose BM groups.Compared with the control group, the expression of the VEGF protein in the renal tissue was significantly decreased in the high-dose BM group (0.76 ±0.09 vs 0.39 ±0.05, P0.05), and the expression of the podocin protein was significantly reduced in the medium-dose BM (0.67 ±0.07 vs 0.43 ±0.10, P0.05).The mRNA expressions of VEGF and podocin were not significantly changed in the low-dose BM group as compared with the control (1.07 ±0.61 and 1.12 ±0.09 vs 1.23 ±0.25 and 1.17 ±0.19, P>0.05) but remarkably de-creased in the medium-dose (0.82 ±0.38 and 0.71 ±0.18) and high-dose BM groups and (0.47 ±0.64 and 0.42 ±0.09) groups (P<0.01). Conclusion Bevacizumab damages glomerular filtration membrane and induce proteinuria partially by down-regulating the protein and mRNA expressions of VEGF and podocin.
ABSTRACT
Objective To evaluate the effects of clinical pathway combined with transitional care implemented by specialty nurses on patients with coronary heart disease after PCI (percutaneous coronary intervention) therapy. Methods Totally 124 patients after PCI were divided into the experimental group and the control group with random digit table. Patients in the control group received routine education and follow- up during hospitalization and discharge period. The experimental group received clinical pathway combined with transitional care implemented by specialty nurses based on routine education. The level of patients′knowledge, attitude, practice and risk factors were compared between the two groups 6 and 12 months after discharge. Results There were 55 patients in each group completed the research ultimately. The Coronary Heart Disease Knowledge Questionnaire in the experimental group scored (57.61 ±8.77), (81.27±6.88) and (88.47±6.10),while the control group scored (59.71±7.32),(68.61±7.12) and (76.85±7.70), after repeated measurement analysis of variance, F=74.71, 14.52, P<0.01. The scores of General Self- Efficacy Scale (GSES) and Coronary Artery Disease Self- Efficacy Scale (CSMS) between two groups at three time points showed statistical significance, F=5.40, 14.52, P<0.05 or 0.01. The risk factors of coronary heart disease such as total cholesterol, triacylglycerol, hemoglobin A1c, body mass index, systolic pressure and diastolic pressure were statistically different between two groups except for high density lipoprotein cholesterol and low density lipoprotein cholesterol, F=5.82, 20.32, 4.14, 4.15, 4.99, 7.15, P<0.05 or 0.01. Conclusions Clinical pathway combined with transitional care implemented by specialty nurses can improve the knowledge-attitude- practice level of patients, help to control the risk factors of coronary heart disease. It is an effective heart rehabilitation model for patients after PCI.