Chuang Yen-Hwang, Chuang Wan-Long, Huang Shu-Pin, Liu Ching-Kuan, Huang Chun-Hsiung
Department of Anatomy, College of Medicine, Kaohsiung Medical University, Kaohsiung 803, Taiwan.
Pharmacol Res. 2009 Oct;60(4):347-57. doi: 10.1016/j.phrs.2009.05.004. Epub 2009 May 22.
Nuclear factor (NF)-kappaB is a ubiquitous transcription factor that can be activated by multiple signals. To elucidate the role of NF-KB and the effects of NF-kappaB inhibitor on ureteric damages in obstructive uropathy, we conducted this study.
The expressions of NF-kappaBp50, NF-kappaBp65, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), proliferation cell nuclear antigen (PCNA) and cell apoptosis were examined in 80 rats. Pyrrolidine dithiocarbamate (PDTC) was administered to 40 rats. The others served as controls.
After ureteric ligation, hydroureter and ureteric damages progressively aggravated. But the severity of hydroureter and fibrosis of muscle layer in the ligated ureters in the treated group were significantly milder than those of the control group. The expressions of NF-kappaBp50 and NFkappa-Bp65 in the smooth muscle layer of obstructed ureters were found in the rats in control group from the day 14 after ureteric ligation. The expressions of NF-kappaBp65 and NF-kappaBp50 in the nuclei of muscle cells in obstructed ureters were correlated significantly with the expressions of IL-6, TNF-alpha, PCNA and the number of the apoptotic cells. The expressions of NF-kappaBp50, NF-kappaBp65 in the nuclei of myocytes and fibrotic changes of smooth muscle layer were correlated significantly. Treatment with PDTC diminished the expressions of NF-kappaBp50 and NF-kappaBp65. The expression of IL-6, TNF-alpha, PCNA and the labeling index of apoptotic cells in the smooth muscle layer of ligated ureters in the PDTC-treated group were also decreased.
We concluded that expression of NF-kappaB might contribute to the ureteric damage in obstructive uropathy, and that inhibition of NF-kB could attenuate the tissue damages of obstructed ureters.
核因子（NF）-κB是一种可被多种信号激活的普遍存在的转录因子。为阐明NF-κB的作用以及NF-κB抑制剂对梗阻性肾病中输尿管损伤的影响，我们开展了本研究。
检测80只大鼠中NF-κBp50、NF-κBp65、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、增殖细胞核抗原（PCNA）的表达及细胞凋亡情况。40只大鼠给予吡咯烷二硫代氨基甲酸盐（PDTC），其余作为对照。
输尿管结扎后，输尿管积水和输尿管损伤逐渐加重。但治疗组结扎输尿管的输尿管积水严重程度及肌层纤维化程度明显轻于对照组。对照组大鼠输尿管结扎后第14天，梗阻输尿管平滑肌层中发现NF-κBp50和NF-κBp65的表达。梗阻输尿管肌细胞核中NF-κBp65和NF-κBp50的表达与IL-6、TNF-α、PCNA的表达及凋亡细胞数量显著相关。肌细胞核中NF-κBp50、NF-κBp65的表达与平滑肌层的纤维化改变显著相关。PDTC治疗可降低NF-κBp50和NF-κBp65的表达。PDTC治疗组结扎输尿管平滑肌层中IL-6、TNF-α、PCNA的表达及凋亡细胞标记指数也降低。
我们得出结论，NF-κB的表达可能导致梗阻性肾病中的输尿管损伤，抑制NF-κB可减轻梗阻输尿管的组织损伤。
