Objective To investigate the expression of p21 and p53 in renal interstitial fibrosis rats and the effect of enalapril on it. Methods Sprague-Dawley rats were randomly divided into 3 groups, shame operation rats group, unilateral urethral obstruction and enalapril treatment group. Histological chan-ges were observed by Masson stain. The expression of p21 mRNA and p53 mRNA was detected by RT-PCR. Results With degree of interstitial fibrosis aggravating, the expression of p21 and p53 increasing,p21 and p53 expression of UUO rats at every time point were positive correlative. Enalapril can inhibit the expression of p21 and p53. Concinsion p21 and p53 expression increased in UUO rats renal cortex and enalapril can significantly inhibit its expression, p21 may participate in the pathogenesis of renal tubule-in-terstitial fibrosis through p53 pathway.

Hematoporphyrin monomethyl ether (HMME) combined with He-Ne laser irradiation is a novel and promising photodynamic therapy (PDT)-induced apoptosis that can be applied in vitro on canine breast cancer cells. However, the exact pathway responsible for HMME-PDT in canine breast cancer cells remains unknown. CHMm cells morphology and apoptosis were analyzed using optical microscope, terminal deoxynucleotidyl transferase dUTP nick end labeling fluorescein staining and DNA ladder assays. Apoptotic pathway was further confirmed by Real-time-polymerase chain reaction and Western blotting assays. Our results showed that HMME-PDT induced significant changes in cell morphology, such as formation of cytoplasmic vacuoles and the gradual rounding of cells coupled with decreased size and detachment. DNA fragmentation and cell death was shown to occur in a time-dependent manner. Furthermore, HMME-PDT increased the activities of caspase-9 and caspase-3, and released cytochrome c from mitochondria into the cytoplasm. HMME-PDT also significantly increased both mRNA and protein levels of Bax and decreased P53 gene expression in a time-dependent manner, while the mRNA and protein expression of Bcl-2 were repressed. These alterations suggest that HMME-PDT induced CHMm cell apoptosis via the mitochondrial apoptosis pathway and had anti-canine breast cancer effects in vitro.
Apoptosis* ; Blotting, Western ; Breast Neoplasms* ; Breast* ; Caspase 3 ; Caspase 9 ; Cell Death ; Cytochromes c ; Cytoplasm ; DNA ; DNA Fragmentation ; DNA Nucleotidylexotransferase ; Ether* ; Fluorescein ; Genes, p53 ; Hematoporphyrins* ; In Vitro Techniques ; Mitochondria ; Photochemotherapy ; RNA, Messenger ; Vacuoles

OBJECTIVE: To explore the effect of p27 in the renal tubule on the process of renal interstitial fibrosis caused by unilateral ureteral obstruction (UUO) in rats, and to examine the expression changes of p27 after enalapril intervention and to interpret the anti-fibrotic mechanism. METHODS: Ninety rats were randomly divided into the sham-operated group (SOR), UUO group,and UUO+enalapril treatment group [enalapril: 10 mg/(kg.d)]. The rats of each group were respectively sacrificed on 7, 14, 21 days post-operatively. The renal pathological changes were dynamically observed by HE. The expression and dynamic changes of p27 were detected by immunohistochemistry. The level of p27 mRNA were detected by RT-PCR. RESULTS: The expression of p27 in renal tubular epithelial cells and p27 mRNA were strongly positive in the SOR group. With degree of interstitial fibrosis aggravating, the expression of p27 mRNA was gradually reducing. Enalapril could improve the expression of p27 on the 14th and 21st days after the UUO. CONCLUSION (1) This study supports a causative role of p27 in the formation of fibrosis of renal mesenchyme in rats with UUO. (2) The anti-fibrotic mechanism of enalapril is partly the improvement of p27 expression.
Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; therapeutic use ; Animals ; Cyclin-Dependent Kinase Inhibitor p27 ; biosynthesis ; genetics ; Enalapril ; pharmacology ; therapeutic use ; Female ; Kidney Tubules ; metabolism ; Nephrosclerosis ; drug therapy ; etiology ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ureteral Obstruction ; complications

OBJECTIVE: To investigate the expression of P21 in renal interstitial fibrosis rats and the effect of enalapril on it. METHODS: Sprague Dawley rats were randomly divided into 3 groups: a sham operation group,a unilateral urethral obstruction group, and an enalapril treatment group. The expression of P21 in renal tubular epithelial cells on the process was detected by immunohistochemistry at different time spots (7, 14, 21 d after UUO, sham-surgery or enalapril treatment). The expression of p21 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Seven days after the surgery, significant differences were found in P21 expression between UUO and SOR renal tubular cells. With degree of interstitial fibrosis aggravating, P21 expression increased. Enalapril can inhibit its expression. CONCLUSION In the kidney of UUO rats, P21 expression increased and enalapril possessed significant inhibitory effects on the procedure. P21 may participate in the pathogenesis of renal tubule-interstitial fibrosis.
Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; therapeutic use ; Animals ; Enalapril ; pharmacology ; therapeutic use ; Kidney Tubules ; metabolism ; Male ; Nephrosclerosis ; drug therapy ; metabolism ; Proto-Oncogene Proteins p21(ras) ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Ureteral Obstruction ; complications