糖尿病大鼠前列腺的形态及基因改变

Morphological and genetic changes in the prostate of rats with diabetes

目的观察糖尿病对大鼠前列腺形态及基因表达的改变。方法链脲霉素（STZ，60mg／kg）诱导糖尿病动物模型，观察前列腺组织形态、筛选表达差异基因及测定8-羟基脱氧鸟苷（8-OHdG）水平。逆转录-聚合酶链反应（RT-PCR）和免疫组织化学染色法验证Mre11和Xrcc3表达差异，并检测高糖（25～75mmol／L）刺激下细胞内活性氧（ROS）强度。结果糖尿病大鼠前列腺形态上出现显著变化。基因芯片发现糖尿病大鼠的前列腺组织中有2304个差异基因，糖尿病大鼠和糖尿病患者前列腺组织中Mrell和Xrcc3的表达均下降，而DNA氧化损伤标记物8-OHdG增加，高糖还可导致细胞内氧化应激水平上升。结论糖尿病可引起前列腺形态异常以及多基因的改蛮。

Objective To investigate the effects of diabetes on the changes of morphology and gene expression in the prostate of rats. Methods Rat diabetic model was induced by STZ （60 mg/kg）. Morphological changes in prostate tissues were examined. Comprehensive genetic expression profiling of control and diabetic rats was analyzed by cDNA microarray. Reverse transcription-polymerase chain reac- tion （RT-PCR） and immunohistochemical staining were used to confirm the changes of Mrell and Xrcc3. The 8-OHdG level in the prostate tissues of rats was detected by enzyme linked immunosorbent assay （ELISA）. Flow cytometry was used to examine the ROS activity induced by high glucose （25-75 mmol/L） in the in vitro cultured prostatic cells. Results Diabetes induced significant morphologic changes in the rat prostate. Microarray analysis revealed that 2304 genes in the diabetic group. Two DNA damage repair genes, Mrel 1 and Xrcc3, were down-regulated in both prostate tissues of diabetic rats and diabetic pa- tients. This was consistent with the increased level of 8-hydroxydeoxyguanosine （8-OHdG）, an oxidative DNA damage marker in the diabetic prostate tissues. Moreover, we found that high glucose caused an in- crease in the level of intracellular oxidative stress. Conclusion Diabetes causes multiple morphological and genetic changes and produces a negative impact on the prostate. Our findings offer important clues for understanding the molecular pathogenesis of the diabetic prostate.