Sönmez Mehmet Fatih, Dündar Munis
a Department of Histology and Embryology, Faculty of Medicine , Erciyes University , Kayseri , Turkey ;
b Department of Medical Genetics, Faculty of Medicine , Erciyes University , Kayseri , Turkey.
Ren Fail. 2016;38(4):605-13. doi: 10.3109/0886022X.2016.1149688. Epub 2016 Feb 24.
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. The NO system has been implicated in the pathogenesis of DN. In this study, we aimed to evaluate the healing effect of pentoxifylline on NOS in STZ-induced diabetic rat's kidney.
In this study, 50 Wistar albino male rats were used. The rats were divided into five groups; Group C control; Group D only diabetes; Group D + PI and D + PII diabetes + pentoxifylline; Group P only pentoxifylline. Group DPI rats received just pentoxifylline from the beginning of the experiments. However, Group DPII rats received saline in the first month and 50 mg/kg/day of pentoxifylline for the following month. At the end of two months, NOS expressions in kidney tissue were assessed using qRT-PCR and immunohistochemistry analysis.
At the end of the experiments, desquamation of the epithelial cells of the tubules, clear glycogen-filled distal tubules and increased number of apoptotic cells were seen in Group D. Diabetic rats' nNOS immunoreactivity had increased and eNOS and iNOS immunoreactivity had decreased; nNOS, iNOS and eNOS mRNA levels tended to decrease compared to the control group. PTX ameliorated eNOS, iNOS and nNOS protein levels and apoptotic cells, but did not affect mRNA levels.
In conclusion, PTX has a healing effect on this damage by affecting NOS expression.
糖尿病肾病（DN）是全球终末期肾病的主要原因。一氧化氮（NO）系统与DN的发病机制有关。在本研究中，我们旨在评估己酮可可碱对链脲佐菌素诱导的糖尿病大鼠肾脏中一氧化氮合酶（NOS）的修复作用。
本研究使用了50只雄性Wistar白化大鼠。大鼠被分为五组：C组为对照组；D组为仅患糖尿病组；D + PI组和D + PII组为糖尿病 + 己酮可可碱组；P组为仅用己酮可可碱组。DPI组大鼠从实验开始就仅接受己酮可可碱。然而，DPII组大鼠在第一个月接受生理盐水，在接下来的一个月接受50mg/kg/天的己酮可可碱。在两个月结束时，使用定量逆转录聚合酶链反应（qRT-PCR）和免疫组织化学分析评估肾组织中NOS的表达。
在实验结束时，D组可见肾小管上皮细胞脱落、远端肾小管充满清晰的糖原以及凋亡细胞数量增加。糖尿病大鼠的神经元型一氧化氮合酶（nNOS）免疫反应性增加，内皮型一氧化氮合酶（eNOS）和诱导型一氧化氮合酶（iNOS）免疫反应性降低；与对照组相比，nNOS、iNOS和eNOS mRNA水平有下降趋势。己酮可可碱改善了eNOS、iNOS和nNOS蛋白水平以及凋亡细胞，但不影响mRNA水平。
总之，己酮可可碱通过影响NOS表达对这种损伤具有修复作用。
