MnTBAP Therapy Attenuates Renal Fibrosis in Mice with 5/6 Nephrectomy.
MnTBAP Therapy Attenuates Renal Fibrosis in Mice with 5/6 Nephrectomy.
复制标题
MnTBAP 疗法可减轻 5/6 肾切除小鼠的肾纤维化
DOI：
10.1155/2016/7496930
复制
发表时间：
2016
影响因子：
--
通讯作者：
Zhang A
中科院分区：
文献类型：
--
作者：
Yu J;Mao S;Zhang Y;Gong W;Jia Z;Huang S;Zhang A
肾纤维化是各种慢性肾脏病（CKD）的共同病理特征，其发生机制尚不明确。越来越多的证据表明，氧化应激在CKD的发病机制中起着重要作用。在这里，我们假设MnTBAP（锰（III）四（4-苯甲酸）卟啉氯化物），超氧化物歧化酶（SOD）的细胞渗透模拟物，可以通过拮抗氧化应激来防止CKD的纤维化反应。为了验证这一假设，我们在肾小管上皮细胞和5/6肾切除术（Nx）小鼠中进行了实验。在小鼠肾小管上皮细胞中，TGF-β1诱导了向纤维化表型的显著转变，这与显著的线粒体功能障碍一致，MnTBAP（1.14 μM）预处理显著改善了这一点。在5/6只Nx小鼠的残肾中，肾小管间质纤维化与肾小管细胞中的线粒体异常平行发生。管理MnTBAP显着衰减的细胞外基质的沉积，证明了阻断表达的纤连蛋白，胶原蛋白I，和胶原蛋白III。Masson染色还显示MnTBAP处理的小鼠中胶原基质的积累得到改善。此外，MnTBAP还显着改善蛋白尿的严重程度，而不改变CKD相关的高血压。总的来说，MnTBAP治疗可能通过拮抗肾脏来源的氧化应激和随后的线粒体功能保护来预防CKD中的肾纤维化，是一种有前途的策略。
Renal fibrosis is a common pathological feature of all kinds of chronic kidney diseases (CKDs) with uncertain mechanisms. Accumulating evidence demonstrated an important role of oxidative stress in the pathogenesis of CKD. Here we hypothesized that MnTBAP (manganese (III) tetrakis (4-benzoic acid)porphyrin chloride), a cell-permeable mimic of superoxide dismutase (SOD), may protect against the fibrotic response in CKD by antagonizing oxidative stress. To verify this hypothesis, we performed experiments in tubular epithelial cells and mice with 5/6 nephrectomy (Nx). In mouse tubular epithelial cells, TGF-β1 induced a significant transition to fibrotic phenotype in line with a remarkable mitochondrial dysfunction, which was markedly improved by MnTBAP (1.14 μM) pretreatment. In remnant kidneys of 5/6 Nx mice, tubulointerstitial fibrosis occurred in parallel with mitochondrial abnormality in renal tubular cells. Administration of MnTBAP significantly attenuated the deposition of extracellular matrix as evidenced by the blocked expressions of fibronectin, collagen I, and collagen III. Masson staining also displayed an ameliorated accumulation of collagenous matrix in MnTBAP-treated mice. Moreover, MnTBAP also significantly improved the severity of proteinuria without altering CKD-related hypertension. Collectively, MnTBAP therapy served as a promising strategy in preventing renal fibrosis in CKDs possibly via antagonizing mitochondrial-derived oxidative stress and subsequent protection of mitochondrial function.