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首页> 美国卫生研究院文献>American Journal of Translational Research >Shenkang injection a modern preparation of Chinese patent medicine diminishes tubulointerstitial fibrosis in obstructive nephropathy via targeting pericyte-myofibroblast transition
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Shenkang injection a modern preparation of Chinese patent medicine diminishes tubulointerstitial fibrosis in obstructive nephropathy via targeting pericyte-myofibroblast transition

机译：申康注射液是现代中成药制剂可通过靶向周细胞-成肌纤维细胞转化来减轻阻塞性肾病中的肾小管间质纤维化

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Shenkang injection (SKI), a modern preparation of Chinese patent medicine, has been widely applied to clinical therapy in the chronic renal failure patients. However, it remains elusive whether SKI can ameliorate tubulointerstitial fibrosis (TIF) in vivo. Recently, pericyte-myofibroblast transition (PMT) plays an important role in the pathogenesis of TIF in obstructive nephropathy (ON). This report thus aims to demonstrate the therapeutic mechanisms of the dose-effects of SKI on TIF by targeting PMT and its signaling activation, compared with imatinib. All rats were divided into 5 groups, the sham-operated group, the vehicle-intervened group, the high dose of SKI-treated group, the low dose of SKI-treated group and the imatinib-treated group. The ON model rats were induced by unilateral ureteral obstruction (UUO), and administered with either the different doses of SKI or imatinib before and after modeling and for a period of 4 weeks. The changes before and after drugs intervention in TIF and PMT markers, and in platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor (VEGFR) signaling pathways activation in the kidneys were analyzed, respectively. As a result, PMT trigger was persistently accompanied with TIF exasperation in the obstructed kidneys after UUO, and that SKI definitely targeted PMT and significantly diminished TIF in vivo. In addition, the high dose of SKI, superior to imatinib, specifically blocked PMT through inhibiting the activation of PDGFR and VEGFR signaling in the kidneys of the UUO model rats. Overall, these findings may further suggest that targeting PMT can provide new strategies for ON treatment.
机译：申康注射液（SKI）是现代中成药制剂，已被广泛应用于慢性肾功能衰竭患者的临床治疗。但是，SKI是否可以改善体内的肾小管间质纤维化（TIF）仍是未知数。最近，周细胞-肌成纤维细胞转化（PMT）在梗阻性肾病（ON）的TIF发病机理中起着重要作用。因此，本报告旨在证明与伊马替尼相比，通过靶向PMT及其信号传导激活，SKI对TIF的剂量效应具有治疗作用。将所有大鼠分为假手术组，媒介物干预组，高剂量SKI治疗组，低剂量SKI治疗组和伊马替尼治疗组5组。通过单侧输尿管梗阻（UUO）诱导ON模型大鼠，并在模型制作前后分别给予不同剂量的SKI或伊马替尼，并持续4周。分别分析了药物干预前后TIF和PMT标记以及肾脏中血小板衍生的生长因子受体（PDGFR）和血管内皮生长因子受体（VEGFR）信号通路激活的变化。结果，在UUO后，阻塞性肾脏中PMT触发持续伴随着TIF激增，而SKI无疑是针对PMT的，并且体内TIF显着降低。此外，优于伊马替尼的高剂量SKI通过抑制UUO模型大鼠肾脏中PDGFR和VEGFR信号的激活，特异性阻断PMT。总体而言，这些发现可能进一步表明靶向PMT可以为ON治疗提供新的策略。

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