Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China.
Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China.
Int Immunopharmacol. 2022 Jan;102:108393. doi: 10.1016/j.intimp.2021.108393. Epub 2021 Nov 30.
Ligusticum striatum DC. is traditionally used to treat ischemic diseases because of its potent effect against blood stasis and thrombosis, including various cardiovascular, cerebral and renal diseases. Senkyunolide I (SEI), which is the major active phthalide ingredient of Ligusticum striatum DC., is mainly distributed in kidney and has been shown to attenuate ischemia reperfusion injury in liver. However, the underlying effect of SEI against renal ischemia-reperfusion injury (IRI) remain unclear.
Renal ischemia reperfusion mice model was established by clamping bilateral renal pedicles. In vitro oxidative stress model was induced by HO. Level of blood urea nitrogen (BUN) and serum creatinine (SCr) was tested for in vivo model evaluation, while cell viability was tested using CCK8 to evaluate in vitro model. SEI solution containing 1% DMSO was injected intraperitoneally in the I/R group, while normal saline containing 1% DMSO injected in the Sham group. Reduced glutathione (GSH) solution containing 1% DMSO was used as a positive control.
SEI protected renal function and structural integrity. It reversed the I/R-induced elevation of BUN, SCr levels and renal pathological injury. The secretion of proinflammatory cytokines including TNF-α and IL-6 was inhibited, and the renal apoptosis was attenuated by SEI. In addition, SEI played a protective role by reducing the production of reactive oxidative species (ROS), as shown by the elevated expression of antioxidant proteins including Nrf2, HO-1, NQO1, and reduced expression of endoplasmic reticulum stress (ERS) related proteins including GRP78 and CHOP. It also attenuated HK2 cell injury in an in vitro model induced by HO.
SEI alleviates renal injury induced by ischemia reperfusion with anti-inflammatory, anti-endoplasmic reticulum stress, anti-oxidative and anti-apoptotic effect.
藁本是一种传统的中药材，具有活血化瘀、通经止痛等功效，常用于治疗心脑血管疾病、脑卒中等疾病。川芎嗪是藁本中的主要活性成分之一，主要分布在肾脏中，具有减轻肝缺血再灌注损伤的作用。然而，川芎嗪对肾脏缺血再灌注损伤（IRI）的作用机制尚不清楚。
采用夹闭双侧肾蒂的方法建立肾脏缺血再灌注小鼠模型，采用 H2O2 诱导建立体外氧化应激模型。通过检测血尿素氮（BUN）和血清肌酐（SCr）水平评估体内模型，通过 CCK8 检测细胞活力评估体外模型。IRI 组小鼠腹腔注射含 1%DMSO 的川芎嗪溶液，Sham 组小鼠腹腔注射含 1%DMSO 的生理盐水。含 1%DMSO 的还原型谷胱甘肽（GSH）溶液作为阳性对照。
川芎嗪能改善肾脏功能和结构完整性，降低 BUN、SCr 水平和肾脏病理损伤程度，减轻 I/R 诱导的炎症反应，减少 TNF-α 和 IL-6 等促炎细胞因子的分泌，减轻肾脏细胞凋亡。此外，川芎嗪通过提高抗氧化蛋白 Nrf2、HO-1、NQO1 的表达，降低内质网应激相关蛋白 GRP78 和 CHOP 的表达，减少活性氧（ROS）的产生，发挥抗炎、抗内质网应激、抗氧化和抗凋亡作用。在 H2O2 诱导的 HK2 细胞损伤的体外模型中，川芎嗪也能减轻 HK2 细胞损伤。
川芎嗪通过抗炎、抗内质网应激、抗氧化和抗凋亡作用减轻缺血再灌注引起的肾脏损伤。
