الملخص
PURPOSE: We investigated the effect of antisense TGF-beta1 oligonucleotides on the expression of TGF-beta1 in the penile corpus cavernosum of streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Forty Sprague-Dawley male rats (200-210 g) were divided into two groups: control (n=10) and experimental group (n=30). The experimental group was received intravenous injection of streptozotocin (50 mg/kg). After 2 weeks, development of diabetes was verified by measuring body weight and blood sugar levels. The experimental group was divided further into 3 groups: vehicle (liposome only), sense oligomer group, and antisense oligomer (5'-CCGAGGGCGGCATGGGGGA-3') group. Penile tissues were used to perform Western analysis and immunohistochemistry for the TGF-beta1 expression. RESULTS: The mean glucose concentrations were 86 9 mg/dl in the control group and 485 119 mg/dl in the experimental group. Downregulation of TGF-beta1 protein expression was noted in the antisense oligomer group compared to sense oligomer group. In the immunohistochemistry, control group showed weak immunoreactivity whereas vehicle or sense oligomer group showed strong immunoreactivity both after 1 and 5 days of treatment. Antisense oligomer treated diabetic group showed weak immunoreactivity similar to control group after 1 day of treatment, even though they showed similar immunoreactivity as vehicle or sense oligomer group after 5 days of treatment. CONCLUSIONS: Antisense TGF-beta1 oligonucleotides suppressed the expression of TGF-beta1 in the corpus cavernosum of diabetic rats. It implies that penile corpus cavernosal fibrosis may be prevented by the application of antisense TGF-beta1 oligonucleotides.
الموضوعات
Animals , Humans , Male , Rats , Blood Glucose , Body Weight , Down-Regulation , Erectile Dysfunction , Fibrosis , Glucose , Immunohistochemistry , Injections, Intravenous , Oligonucleotides , Rats, Sprague-Dawley , Streptozocin , Transforming Growth Factor beta1الملخص
To date, most of data regarding H/K-ATPase have been derived from alterations of gene expression or enzymatic activity in kidney. But potassium balance is achieved by the control of urinary K+ excretion and by the control of K+ absorption from the digestive tract. The digestive system is also expected to participate substantively in the regulation of systemic K+ homeostasis during chronic hypokalemia. This study was performed to analyze the expression and distribution of the gastric H/K-ATPase alpha subunit mRNA and protein in rats of chronic changes of potassium diet using Northern blot analysis and immunohistochemistry. Northern blot analysis demonstrate that gastric H/K- ATPase alpha subunit mRNA was abundantly expressed in normal rat stomach not in distal colon. In experimental groups, gastric H/K-ATPase alpha subunit mRNA was also abundantly expressed, but there was no significant differences among all groups. By immunohistochemistry, immunoreactivity of gastric H/K-ATPase alpha subunit was detected in the parietal cells. Reaction products were diffusely localized throughout the cytoplasm. Most of these immunoreactive cells were located in the gastric gland between the neck and base portion of the body, but a few cells in the base or gastric pits. All groups exhibited comparable cellular patterns of labeling and signal intensity. These results suggest that gastric H/K-ATPase alpha subunit does not significantly contribute to potassium conservation during chronic changes of potassium diet in spite of abundant expression.