Bushen Huoxue Recipe Inhibits Renal Fibrosis by Regulating the Reactive Oxygen Species/Nucleotide-Binding Oligomerization Domain-Like Receptor Family Pyrin Domain-Containing 3-Induced Pyroptosis Pathway

Xian Chen, Jianrao Lu
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Abstract

To probe the role and specific mechanism of Bushen Huoxue Recipe in inhibiting renal fibrosis (RF), 150 healthy adult male Sprague-Dawley rats were randomized to sham operated group (SO group), model group (UUO group), conventional treatment group (UUO+EPL group), high-dose Bushen Huoxuefang group (UUO+H group), and low-dose Bushen Huoxue Recipe group (UUO+L group), with 30 mice in each group. The UUO, UUO+EPL, UUO+H, and UUO+L groups showed decreased pathological damage scores in rat renal tissue and increased blood urea nitrogen (BUN), serum creatinine (Cr), interleukin-1β (IL-1β), IL-18, high-sensitivity C-reactive protein (hs-CRP), and caspase-1 levels compared with the SO group. The expression of NLRP3, type III collagen (Col-III), matrix fibronectin (FN), and α-smooth actin (α-SMA) increased (P <0.05). Inflammatory cells aggregated in rat kidney tissue, and some renal tubular cells atrophied, fell off, vacuolized, underwent pyknosis, and the shape of tubules was incomplete. The lumen was enlarged, and the DNA damage was greater. The UUO+EPL, UUO+H and UUO+L groups showed increased pathological damage score of rat renal tissue and decreased expression levels of Cr, BUN, hs-CRP, IL-1β, IL-18, caspase-1, NLRP3, FN, Col-III, and α-SMA than UUO group. After a longer period, the UUO+EPL and UUO+H groups decreased more significantly than the UUO+L group. We conclude that Bushen Huoxue Recipe inhibits RF by regulating reactive oxygen species (ROS)/NLRP3-induced pyroptosis pathway.
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补肾活血方通过调节活性氧/核苷酸结合寡聚结构域样受体家族Pyrin结构域3诱导的Pyroptosis通路抑制肾纤维化
为探讨补肾活血方抑制肾纤维化(RF)的作用及具体机制,将150只健康成年雄性sd大鼠随机分为假手术组(SO组)、模型组(UUO组)、常规治疗组(UUO+EPL组)、补肾活血方高剂量组(UUO+H组)、补肾活血方低剂量组(UUO+L组),每组30只。与SO组相比,UUO、UUO+EPL、UUO+H和UUO+L组大鼠肾组织病理损伤评分降低,血尿素氮(BUN)、血清肌酐(Cr)、白细胞介素-1β (IL-1β)、IL-18、高敏c反应蛋白(hs-CRP)和caspase-1水平升高。NLRP3、ⅲ型胶原(Col-III)、基质纤维连接蛋白(FN)、α-光滑肌动蛋白(α-SMA)表达升高(P <0.05)。炎症细胞在大鼠肾组织内聚集,部分肾小管细胞萎缩、脱落、空泡化、固缩,小管形态不完整。管腔增大,DNA损伤更大。UUO+EPL、UUO+H、UUO+L组大鼠肾组织病理损伤评分均高于UUO组,Cr、BUN、hs-CRP、IL-1β、IL-18、caspase-1、NLRP3、FN、Col-III、α-SMA表达水平低于UUO组。较长时间后,UUO+EPL组和UUO+H组较UUO+L组下降更明显。我们认为补肾活血方通过调节活性氧(ROS)/ nlrp3诱导的焦亡途径抑制RF。
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